A z-Vertex Trigger for Belle II

NASA Astrophysics Data System (ADS)

Skambraks, S.; Abudinén, F.; Chen, Y.; Feindt, M.; Frühwirth, R.; Heck, M.; Kiesling, C.; Knoll, A.; Neuhaus, S.; Paul, S.; Schieck, J.

2015-08-01

The Belle II experiment will go into operation at the upgraded SuperKEKB collider in 2016. SuperKEKB is designed to deliver an instantaneous luminosity L = 8 ×1035 cm - 2 s - 1. The experiment will therefore have to cope with a much larger machine background than its predecessor Belle, in particular from events outside of the interaction region. We present the concept of a track trigger, based on a neural network approach, that is able to suppress a large fraction of this background by reconstructing the z (longitudinal) position of the event vertex within the latency of the first level trigger. The trigger uses the hit information from the Central Drift Chamber (CDC) of Belle II within narrow cones in polar and azimuthal angle as well as in transverse momentum (“sectors”), and estimates the z-vertex without explicit track reconstruction. The preprocessing for the track trigger is based on the track information provided by the standard CDC trigger. It takes input from the 2D track finder, adds information from the stereo wires of the CDC, and finds the appropriate sectors in the CDC for each track. Within the sector, the z-vertex is estimated by a specialized neural network, with the drift times from the CDC as input and a continuous output corresponding to the scaled z-vertex. The neural algorithm will be implemented in programmable hardware. To this end a Virtex 7 FPGA board will be used, which provides at present the most promising solution for a fully parallelized implementation of neural networks or alternative multivariate methods. A high speed interface for external memory will be integrated into the platform, to be able to store the O(109) parameters required. The contribution presents the results of our feasibility studies and discusses the details of the envisaged hardware solution.

A review on the neural bases of episodic odor memory: from laboratory-based to autobiographical approaches

PubMed Central

Saive, Anne-Lise; Royet, Jean-Pierre; Plailly, Jane

2014-01-01

Odors are powerful cues that trigger episodic memories. However, in light of the amount of behavioral data describing the characteristics of episodic odor memory, the paucity of information available on the neural substrates of this function is startling. Furthermore, the diversity of experimental paradigms complicates the identification of a generic episodic odor memory network. We conduct a systematic review of the literature depicting the current state of the neural correlates of episodic odor memory in healthy humans by placing a focus on the experimental approaches. Functional neuroimaging data are introduced by a brief characterization of the memory processes investigated. We present and discuss laboratory-based approaches, such as odor recognition and odor associative memory, and autobiographical approaches, such as the evaluation of odor familiarity and odor-evoked autobiographical memory. We then suggest the development of new laboratory-ecological approaches allowing for the controlled encoding and retrieval of specific multidimensional events that could open up new prospects for the comprehension of episodic odor memory and its neural underpinnings. While large conceptual differences distinguish experimental approaches, the overview of the functional neuroimaging findings suggests relatively stable neural correlates of episodic odor memory. PMID:25071494

Neuro-cognitive mechanisms of decision making in joint action: a human-robot interaction study.

PubMed

Bicho, Estela; Erlhagen, Wolfram; Louro, Luis; e Silva, Eliana Costa

2011-10-01

In this paper we present a model for action preparation and decision making in cooperative tasks that is inspired by recent experimental findings about the neuro-cognitive mechanisms supporting joint action in humans. It implements the coordination of actions and goals among the partners as a dynamic process that integrates contextual cues, shared task knowledge and predicted outcome of others' motor behavior. The control architecture is formalized by a system of coupled dynamic neural fields representing a distributed network of local but connected neural populations. Different pools of neurons encode task-relevant information about action means, task goals and context in the form of self-sustained activation patterns. These patterns are triggered by input from connected populations and evolve continuously in time under the influence of recurrent interactions. The dynamic model of joint action is evaluated in a task in which a robot and a human jointly construct a toy object. We show that the highly context sensitive mapping from action observation onto appropriate complementary actions allows coping with dynamically changing joint action situations. Copyright © 2010 Elsevier B.V. All rights reserved.

Unjoined primary and secondary neural tubes: junctional neural tube defect, a new form of spinal dysraphism caused by disturbance of junctional neurulation.

PubMed

Eibach, Sebastian; Moes, Greg; Hou, Yong Jin; Zovickian, John; Pang, Dachling

2017-10-01

Primary and secondary neurulation are the two known processes that form the central neuraxis of vertebrates. Human phenotypes of neural tube defects (NTDs) mostly fall into two corresponding categories consistent with the two types of developmental sequence: primary NTD features an open skin defect, an exposed, unclosed neural plate (hence an open neural tube defect, or ONTD), and an unformed or poorly formed secondary neural tube, and secondary NTD with no skin abnormality (hence a closed NTD) and a malformed conus caudal to a well-developed primary neural tube. We encountered three cases of a previously unrecorded form of spinal dysraphism in which the primary and secondary neural tubes are individually formed but are physically separated far apart and functionally disconnected from each other. One patient was operated on, in whom both the lumbosacral spinal cord from primary neurulation and the conus from secondary neurulation are each anatomically complete and endowed with functioning segmental motor roots tested by intraoperative triggered electromyography and direct spinal cord stimulation. The remarkable feature is that the two neural tubes are unjoined except by a functionally inert, probably non-neural band. The developmental error of this peculiar malformation probably occurs during the critical transition between the end of primary and the beginning of secondary neurulation, in a stage aptly called junctional neurulation. We describe the current knowledge concerning junctional neurulation and speculate on the embryogenesis of this new class of spinal dysraphism, which we call junctional neural tube defect.

Salient sounds activate human visual cortex automatically.

PubMed

McDonald, John J; Störmer, Viola S; Martinez, Antigona; Feng, Wenfeng; Hillyard, Steven A

2013-05-22

Sudden changes in the acoustic environment enhance perceptual processing of subsequent visual stimuli that appear in close spatial proximity. Little is known, however, about the neural mechanisms by which salient sounds affect visual processing. In particular, it is unclear whether such sounds automatically activate visual cortex. To shed light on this issue, this study examined event-related brain potentials (ERPs) that were triggered either by peripheral sounds that preceded task-relevant visual targets (Experiment 1) or were presented during purely auditory tasks (Experiments 2-4). In all experiments the sounds elicited a contralateral ERP over the occipital scalp that was localized to neural generators in extrastriate visual cortex of the ventral occipital lobe. The amplitude of this cross-modal ERP was predictive of perceptual judgments about the contrast of colocalized visual targets. These findings demonstrate that sudden, intrusive sounds reflexively activate human visual cortex in a spatially specific manner, even during purely auditory tasks when the sounds are not relevant to the ongoing task.

Salient sounds activate human visual cortex automatically

PubMed Central

McDonald, John J.; Störmer, Viola S.; Martinez, Antigona; Feng, Wenfeng; Hillyard, Steven A.

2013-01-01

Sudden changes in the acoustic environment enhance perceptual processing of subsequent visual stimuli that appear in close spatial proximity. Little is known, however, about the neural mechanisms by which salient sounds affect visual processing. In particular, it is unclear whether such sounds automatically activate visual cortex. To shed light on this issue, the present study examined event-related brain potentials (ERPs) that were triggered either by peripheral sounds that preceded task-relevant visual targets (Experiment 1) or were presented during purely auditory tasks (Experiments 2, 3, and 4). In all experiments the sounds elicited a contralateral ERP over the occipital scalp that was localized to neural generators in extrastriate visual cortex of the ventral occipital lobe. The amplitude of this cross-modal ERP was predictive of perceptual judgments about the contrast of co-localized visual targets. These findings demonstrate that sudden, intrusive sounds reflexively activate human visual cortex in a spatially specific manner, even during purely auditory tasks when the sounds are not relevant to the ongoing task. PMID:23699530

What Neural Substrates Trigger the Adept Scientific Pattern Discovery by Biologists?

ERIC Educational Resources Information Center

Lee, Jun-Ki; Kwon, Yong-Ju

2011-01-01

This study investigated the neural correlates of experts and novices during biological object pattern detection using an fMRI approach in order to reveal the neural correlates of a biologist's superior pattern discovery ability. Sixteen healthy male participants (8 biologists and 8 non-biologists) volunteered for the study. Participants were shown…

Decentralized event-triggered synchronization of uncertain Markovian jumping neutral-type neural networks with mixed delays.

PubMed

Senan, Sibel; Syed Ali, M; Vadivel, R; Arik, Sabri

2017-02-01

In this study, we present an approach for the decentralized event-triggered synchronization of Markovian jumping neutral-type neural networks with mixed delays. We present a method for designing decentralized event-triggered synchronization, which only utilizes locally available information, in order to determine the time instants for transmission from sensors to a central controller. By applying a novel Lyapunov-Krasovskii functional, as well as using the reciprocal convex combination method and some inequality techniques such as Jensen's inequality, we obtain several sufficient conditions in terms of a set of linear matrix inequalities (LMIs) under which the delayed neural networks are stochastically stable in terms of the error systems. Finally, we conclude that the drive systems synchronize stochastically with the response systems. We show that the proposed stability criteria can be verified easily using the numerically efficient Matlab LMI toolbox. The effectiveness and feasibility of the results obtained are verified by numerical examples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neural assembly computing.

PubMed

Ranhel, João

2012-06-01

Spiking neurons can realize several computational operations when firing cooperatively. This is a prevalent notion, although the mechanisms are not yet understood. A way by which neural assemblies compute is proposed in this paper. It is shown how neural coalitions represent things (and world states), memorize them, and control their hierarchical relations in order to perform algorithms. It is described how neural groups perform statistic logic functions as they form assemblies. Neural coalitions can reverberate, becoming bistable loops. Such bistable neural assemblies become short- or long-term memories that represent the event that triggers them. In addition, assemblies can branch and dismantle other neural groups generating new events that trigger other coalitions. Hence, such capabilities and the interaction among assemblies allow neural networks to create and control hierarchical cascades of causal activities, giving rise to parallel algorithms. Computing and algorithms are used here as in a nonstandard computation approach. In this sense, neural assembly computing (NAC) can be seen as a new class of spiking neural network machines. NAC can explain the following points: 1) how neuron groups represent things and states; 2) how they retain binary states in memories that do not require any plasticity mechanism; and 3) how branching, disbanding, and interaction among assemblies may result in algorithms and behavioral responses. Simulations were carried out and the results are in agreement with the hypothesis presented. A MATLAB code is available as a supplementary material.

Track vertex reconstruction with neural networks at the first level trigger of Belle II

NASA Astrophysics Data System (ADS)

Neuhaus, Sara; Skambraks, Sebastian; Kiesling, Christian

2017-08-01

The track trigger is one of the main components of the Belle II first level trigger, taking input from the Central Drift Chamber (CDC). It consists of several stages, first combining hits to track segments, followed by a 2D track finding in the transverse plane and finally a 3D track reconstruction. The results of the track trigger are the track multiplicity, the momentum vector of each track and the longitudinal displacement of the origin or production vertex of each track ("z-vertex"). The latter allows to reject background tracks from outside of the interaction region and thus to suppress a large fraction of the machine background. This contribution focuses on the track finding stage using Hough transforms and on the z-vertex reconstruction with neural networks. We describe the algorithms and show performance studies on simulated events.

Brain computer interface to enhance episodic memory in human participants

PubMed Central

Burke, John F.; Merkow, Maxwell B.; Jacobs, Joshua; Kahana, Michael J.

2015-01-01

Recent research has revealed that neural oscillations in the theta (4–8 Hz) and alpha (9–14 Hz) bands are predictive of future success in memory encoding. Because these signals occur before the presentation of an upcoming stimulus, they are considered stimulus-independent in that they correlate with enhanced memory encoding independent of the item being encoded. Thus, such stimulus-independent activity has important implications for the neural mechanisms underlying episodic memory as well as the development of cognitive neural prosthetics. Here, we developed a brain computer interface (BCI) to test the ability of such pre-stimulus activity to modulate subsequent memory encoding. We recorded intracranial electroencephalography (iEEG) in neurosurgical patients as they performed a free recall memory task, and detected iEEG theta and alpha oscillations that correlated with optimal memory encoding. We then used these detected oscillatory changes to trigger the presentation of items in the free recall task. We found that item presentation contingent upon the presence of pre-stimulus theta and alpha oscillations modulated memory performance in more sessions than expected by chance. Our results suggest that an electrophysiological signal may be causally linked to a specific behavioral condition, and contingent stimulus presentation has the potential to modulate human memory encoding. PMID:25653605

The biology of mammalian parenting and its effect on offspring social development.

PubMed

Rilling, James K; Young, Larry J

2014-08-15

Parents know the transformative nature of having and caring for a child. Among many mammals, giving birth leads from an aversion to infant stimuli to irresistible attraction. Here, we review the biological mechanisms governing this shift in parental motivation in mammals. Estrogen and progesterone prepare the uterus for embryo implantation and placental development. Prolactin stimulates milk production, whereas oxytocin initiates labor and triggers milk ejection during nursing. These same molecules, interacting with dopamine, also activate specific neural pathways to motivate parents to nurture, bond with, and protect their offspring. Parenting in turn shapes the neural development of the infant social brain. Recent work suggests that many of the principles governing parental behavior and its effect on infant development are conserved from rodent to humans. Copyright © 2014, American Association for the Advancement of Science.

High Aspect-Ratio Neural Probes using Conventional Blade Dicing

NASA Astrophysics Data System (ADS)

Goncalves, S. B.; Ribeiro, J. F.; Silva, A. F.; Correia, J. H.

2016-10-01

Exploring deep neural circuits has triggered the development of long penetrating neural probes. Moreover, driven by brain displacement, the long neural probes require also a high aspect-ratio shafts design. In this paper, a simple and reproducible method of manufacturing long-shafts neural probes using blade dicing technology is presented. Results shows shafts up to 8 mm long and 200 µm wide, features competitive to the current state-of-art, being its outline simply accomplished by a single blade dicing program. Therefore, conventional blade dicing presents itself as a viable option to manufacture long neural probes.

The neural basis of deception in strategic interactions

PubMed Central

Volz, Kirsten G.; Vogeley, Kai; Tittgemeyer, Marc; von Cramon, D. Yves; Sutter, Matthias

2015-01-01

Communication based on informational asymmetries abounds in politics, business, and almost any other form of social interaction. Informational asymmetries may create incentives for the better-informed party to exploit her advantage by misrepresenting information. Using a game-theoretic setting, we investigate the neural basis of deception in human interaction. Unlike in most previous fMRI research on deception, the participants decide themselves whether to lie or not. We find activation within the right temporo-parietal junction (rTPJ), the dorsal anterior cingulate cortex (ACC), the (pre)cuneus (CUN), and the anterior frontal gyrus (aFG) when contrasting lying with truth telling. Notably, our design also allows for an investigation of the neural foundations of sophisticated deception through telling the truth—when the sender does not expect the receiver to believe her (true) message. Sophisticated deception triggers activation within the same network as plain lies, i.e., we find activity within the rTPJ, the CUN, and aFG. We take this result to show that brain activation can reveal the sender's veridical intention to deceive others, irrespective of whether in fact the sender utters the factual truth or not. PMID:25729358

The neural basis of deception in strategic interactions.

PubMed

Volz, Kirsten G; Vogeley, Kai; Tittgemeyer, Marc; von Cramon, D Yves; Sutter, Matthias

2015-01-01

Communication based on informational asymmetries abounds in politics, business, and almost any other form of social interaction. Informational asymmetries may create incentives for the better-informed party to exploit her advantage by misrepresenting information. Using a game-theoretic setting, we investigate the neural basis of deception in human interaction. Unlike in most previous fMRI research on deception, the participants decide themselves whether to lie or not. We find activation within the right temporo-parietal junction (rTPJ), the dorsal anterior cingulate cortex (ACC), the (pre)cuneus (CUN), and the anterior frontal gyrus (aFG) when contrasting lying with truth telling. Notably, our design also allows for an investigation of the neural foundations of sophisticated deception through telling the truth-when the sender does not expect the receiver to believe her (true) message. Sophisticated deception triggers activation within the same network as plain lies, i.e., we find activity within the rTPJ, the CUN, and aFG. We take this result to show that brain activation can reveal the sender's veridical intention to deceive others, irrespective of whether in fact the sender utters the factual truth or not.

Translational Research on Habit and Alcohol.

PubMed

McKim, Theresa H; Shnitko, Tatiana A; Robinson, Donita L; Boettiger, Charlotte A

2016-03-01

Habitual actions enable efficient daily living, but they can also contribute to pathological behaviors that resistant change, such as alcoholism. Habitual behaviors are learned actions that appear goal-directed but are in fact no longer under the control of the action's outcome. Instead, these actions are triggered by stimuli, which may be exogenous or interoceptive, discrete or contextual. A major hallmark characteristic of alcoholism is continued alcohol use despite serious negative consequences. In essence, although the outcome of alcohol seeking and drinking is dramatically devalued, these actions persist, often triggered by environmental cues associated with alcohol use. Thus, alcoholism meets the definition of an initially goal-directed behavior that converts to a habit-based process. Habit and alcohol have been well investigated in rodent models, with comparatively less research in non-human primates and people. This review focuses on translational research on habit and alcohol with an emphasis on cross-species methodology and neural circuitry.

Muon Trigger for Mobile Phones

NASA Astrophysics Data System (ADS)

Borisyak, M.; Usvyatsov, M.; Mulhearn, M.; Shimmin, C.; Ustyuzhanin, A.

2017-10-01

The CRAYFIS experiment proposes to use privately owned mobile phones as a ground detector array for Ultra High Energy Cosmic Rays. Upon interacting with Earth’s atmosphere, these events produce extensive particle showers which can be detected by cameras on mobile phones. A typical shower contains minimally-ionizing particles such as muons. As these particles interact with CMOS image sensors, they may leave tracks of faintly-activated pixels that are sometimes hard to distinguish from random detector noise. Triggers that rely on the presence of very bright pixels within an image frame are not efficient in this case. We present a trigger algorithm based on Convolutional Neural Networks which selects images containing such tracks and are evaluated in a lazy manner: the response of each successive layer is computed only if activation of the current layer satisfies a continuation criterion. Usage of neural networks increases the sensitivity considerably comparable with image thresholding, while the lazy evaluation allows for execution of the trigger under the limited computational power of mobile phones.

Illusory Obesity Triggers Body Dissatisfaction Responses in the Insula and Anterior Cingulate Cortex

PubMed Central

Preston, Catherine; Ehrsson, H. Henrik

2016-01-01

In today's Western society, concerns regarding body size and negative feelings toward one's body are all too common. However, little is known about the neural mechanisms underlying negative feelings toward the body and how they relate to body perception and eating-disorder pathology. Here, we used multisensory illusions to elicit illusory ownership of obese and slim bodies during functional magnetic resonance imaging. The results implicate the anterior insula and the anterior cingulate cortex in the development of negative feelings toward the body through functional interactions with the posterior parietal cortex, which mediates perceived obesity. Moreover, cingulate neural responses were modulated by nonclinical eating-disorder psychopathology and were attenuated in females. These results reveal how perceptual and affective body representations interact in the human brain and may help explain the neurobiological underpinnings of eating-disorder vulnerability in women. PMID:27733537

Building-associated neurological damage modeled in human cells: a mechanism of neurotoxic effects by exposure to mycotoxins in the indoor environment.

PubMed

Karunasena, Enusha; Larrañaga, Michael D; Simoni, Jan S; Douglas, David R; Straus, David C

2010-12-01

Damage to human neurological system cells resulting from exposure to mycotoxins confirms a previously controversial public health threat for occupants of water-damaged buildings. Leading scientific organizations disagree about the ability of inhaled mycotoxins in the indoor environment to cause adverse human health effects. Damage to the neurological system can result from exposure to trichothecene mycotoxins in the indoor environment. This study demonstrates that neurological system cell damage can occur from satratoxin H exposure to neurological cells at exposure levels that can be found in water-damaged buildings contaminated with fungal growth. The constant activation of inflammatory and apoptotic pathways at low levels of exposure in human brain capillary endothelial cells, astrocytes, and neural progenitor cells may amplify devastation to neurological tissues and lead to neurological system cell damage from indirect events triggered by the presence of trichothecenes.

Developmental neurotoxicity screening using human embryonic stem cells.

PubMed

Bosnjak, Zeljko J

2012-09-01

Research in the area of stem cell biology and regenerative medicine, along with neuroscience, will further our understanding of drug-induced death of neurons during their development. With the development of an in vitro model of stem cell-derived human neural cell lines investigators can, under control conditions and during intense neuronal growth, examine molecular mechanisms of various drugs and conditions on early developmental neuroapoptosis in humans. If the use of this model will lead to fewer risks, or identification of drugs and anesthetics that are less likely to cause the death of neurons, this approach will be a major stride toward assuring the safety of drugs during the brain development. The ultimate goal would be not only to find the trigger for the catastrophic chain of events, but also to prevent neuronal cell death itself. Copyright © 2012. Published by Elsevier Inc.

Neural Mechanisms Underlying Conscious and Unconscious Gaze-Triggered Attentional Orienting in Autism Spectrum Disorder

PubMed Central

Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Yoshimura, Sayaka; Toichi, Motomi

2017-01-01

Impaired joint attention represents the core clinical feature of autism spectrum disorder (ASD). Behavioral studies have suggested that gaze-triggered attentional orienting is intact in response to supraliminally presented eyes but impaired in response to subliminally presented eyes in individuals with ASD. However, the neural mechanisms underlying conscious and unconscious gaze-triggered attentional orienting remain unclear. We investigated this issue in ASD and typically developing (TD) individuals using event-related functional magnetic resonance imaging. The participants viewed cue stimuli of averted or straight eye gaze direction presented either supraliminally or subliminally and then localized a target. Reaction times were shorter when eye-gaze cues were directionally valid compared with when they were neutral under the supraliminal condition in both groups; the same pattern was found in the TD group but not the ASD group under the subliminal condition. The temporo–parieto–frontal regions showed stronger activation in response to averted eyes than to straight eyes in both groups under the supraliminal condition. The left amygdala was more activated while viewing averted vs. straight eyes in the TD group than in the ASD group under the subliminal condition. These findings provide an explanation for the neural mechanisms underlying the impairment in unconscious but not conscious gaze-triggered attentional orienting in individuals with ASD and suggest possible neurological and behavioral interventions to facilitate their joint attention behaviors. PMID:28701942

Functionalizing Ascl1 with Novel Intracellular Protein Delivery Technology for Promoting Neuronal Differentiation of Human Induced Pluripotent Stem Cells.

PubMed

Robinson, Meghan; Chapani, Parv; Styan, Tara; Vaidyanathan, Ranjani; Willerth, Stephanie Michelle

2016-08-01

Pluripotent stem cells can become any cell type found in the body. Accordingly, one of the major challenges when working with pluripotent stem cells is producing a highly homogenous population of differentiated cells, which can then be used for downstream applications such as cell therapies or drug screening. The transcription factor Ascl1 plays a key role in neural development and previous work has shown that Ascl1 overexpression using viral vectors can reprogram fibroblasts directly into neurons. Here we report on how a recombinant version of the Ascl1 protein functionalized with intracellular protein delivery technology (Ascl1-IPTD) can be used to rapidly differentiate human induced pluripotent stem cells (hiPSCs) into neurons. We first evaluated a range of Ascl1-IPTD concentrations to determine the most effective amount for generating neurons from hiPSCs cultured in serum free media. Next, we looked at the frequency of Ascl1-IPTD supplementation in the media on differentiation and found that one time supplementation is sufficient enough to trigger the neural differentiation process. Ascl1-IPTD was efficiently taken up by the hiPSCs and enabled rapid differentiation into TUJ1-positive and NeuN-positive populations with neuronal morphology after 8 days. After 12 days of culture, hiPSC-derived neurons produced by Ascl1-IPTD treatment exhibited greater neurite length and higher numbers of branch points compared to neurons derived using a standard neural progenitor differentiation protocol. This work validates Ascl1-IPTD as a powerful tool for engineering neural tissue from pluripotent stem cells.

The Eyes Have It! An fMRI Investigation

ERIC Educational Resources Information Center

Kingstone, Alan; Tipper, Christine; Ristic, Jelena; Ngan, Elton

2004-01-01

For the past several years it has been thought that cues, such as eye direction, can trigger reflexive shifts in attention because of their biological relevance and their specialized neural architecture. However, very recently, Ristic, Friesen, and Kingstone (2002) reported that other stimuli, such as arrows, trigger reflexive shifts in attention…

Neural Basis of Visual Distraction

ERIC Educational Resources Information Center

Kim, So-Yeon; Hopfinger, Joseph B.

2010-01-01

The ability to maintain focus and avoid distraction by goal-irrelevant stimuli is critical for performing many tasks and may be a key deficit in attention-related problems. Recent studies have demonstrated that irrelevant stimuli that are consciously perceived may be filtered out on a neural level and not cause the distraction triggered by…

Reconstruction of Micropattern Detector Signals using Convolutional Neural Networks

NASA Astrophysics Data System (ADS)

Flekova, L.; Schott, M.

2017-10-01

Micropattern gaseous detector (MPGD) technologies, such as GEMs or MicroMegas, are particularly suitable for precision tracking and triggering in high rate environments. Given their relatively low production costs, MPGDs are an exemplary candidate for the next generation of particle detectors. Having acknowledged these advantages, both the ATLAS and CMS collaborations at the LHC are exploiting these new technologies for their detector upgrade programs in the coming years. When MPGDs are utilized for triggering purposes, the measured signals need to be precisely reconstructed within less than 200 ns, which can be achieved by the usage of FPGAs. In this work, we present a novel approach to identify reconstructed signals, their timing and the corresponding spatial position on the detector. In particular, we study the effect of noise and dead readout strips on the reconstruction performance. Our approach leverages the potential of convolutional neural network (CNNs), which have recently manifested an outstanding performance in a range of modeling tasks. The proposed neural network architecture of our CNN is designed simply enough, so that it can be modeled directly by an FPGA and thus provide precise information on reconstructed signals already in trigger level.

Event Boundaries Trigger Rapid Memory Reinstatement of the Prior Events to Promote Their Representation in Long-Term Memory.

PubMed

Sols, Ignasi; DuBrow, Sarah; Davachi, Lila; Fuentemilla, Lluís

2017-11-20

Although everyday experiences unfold continuously over time, shifts in context, or event boundaries, can influence how those events come to be represented in memory [1-4]. Specifically, mnemonic binding across sequential representations is more challenging at context shifts, such that successful temporal associations are more likely to be formed within than across contexts [1, 2, 5-9]. However, in order to preserve a subjective sense of continuity, it is important that the memory system bridge temporally adjacent events, even if they occur in seemingly distinct contexts. Here, we used pattern similarity analysis to scalp electroencephalographic (EEG) recordings during a sequential learning task [2, 3] in humans and showed that the detection of event boundaries triggered a rapid memory reinstatement of the just-encoded sequence episode. Memory reactivation was detected rapidly (∼200-800 ms from the onset of the event boundary) and was specific to context shifts that were preceded by an event sequence with episodic content. Memory reinstatement was not observed during the sequential encoding of events within an episode, indicating that memory reactivation was induced specifically upon context shifts. Finally, the degree of neural similarity between neural responses elicited during sequence encoding and at event boundaries correlated positively with participants' ability to later link across sequences of events, suggesting a critical role in binding temporally adjacent events in long-term memory. Current results shed light onto the neural mechanisms that promote episodic encoding not only for information within the event, but also, importantly, in the ability to link across events to create a memory representation of continuous experience. Copyright © 2017 Elsevier Ltd. All rights reserved.

How Does the Sparse Memory “Engram” Neurons Encode the Memory of a Spatial–Temporal Event?

PubMed Central

Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

2016-01-01

Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns. PMID:27601979

How Does the Sparse Memory "Engram" Neurons Encode the Memory of a Spatial-Temporal Event?

PubMed

Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

2016-01-01

Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns.

Event-triggered H∞ state estimation for semi-Markov jumping discrete-time neural networks with quantization.

PubMed

Rakkiyappan, R; Maheswari, K; Velmurugan, G; Park, Ju H

2018-05-17

This paper investigates H ∞ state estimation problem for a class of semi-Markovian jumping discrete-time neural networks model with event-triggered scheme and quantization. First, a new event-triggered communication scheme is introduced to determine whether or not the current sampled sensor data should be broad-casted and transmitted to the quantizer, which can save the limited communication resource. Second, a novel communication framework is employed by the logarithmic quantizer that quantifies and reduces the data transmission rate in the network, which apparently improves the communication efficiency of networks. Third, a stabilization criterion is derived based on the sufficient condition which guarantees a prescribed H ∞ performance level in the estimation error system in terms of the linear matrix inequalities. Finally, numerical simulations are given to illustrate the correctness of the proposed scheme. Copyright © 2018 Elsevier Ltd. All rights reserved.

Consistent chronostasis effects across saccade categories imply a subcortical efferent trigger

PubMed Central

Yarrow, Kielan; Johnson, Helen; Haggard, Patrick; Rothwell, John C

2005-01-01

Saccadic chronostasis refers to the subjective temporal lengthening of the first visual stimulus perceived after an eye movement, and is most commonly experienced as the “stopped clock” illusion. Other temporal illusions arising in the context of movement (e.g. “intentional binding”) appear to depend upon the volitional nature of the preceding motor act. Here we assess chronostasis across different saccade types, ranging from highly volitional (self-timed saccades, anti saccades) to highly reflexive (peripherally-cued saccades, express saccades). Chronostasis was similar in magnitude across all these conditions, despite wide variations in their neural bases. The illusion must therefore be triggered by a “lowest common denominator” signal common to all the conditions tested and their respective neural circuits. Specifically, it is suggested that chronostasis is triggered by a low-level signal arising in response to efferent signals generated in the superior colliculus. PMID:15200711

Event Recognition Based on Deep Learning in Chinese Texts

PubMed Central

Zhang, Yajun; Liu, Zongtian; Zhou, Wen

2016-01-01

Event recognition is the most fundamental and critical task in event-based natural language processing systems. Existing event recognition methods based on rules and shallow neural networks have certain limitations. For example, extracting features using methods based on rules is difficult; methods based on shallow neural networks converge too quickly to a local minimum, resulting in low recognition precision. To address these problems, we propose the Chinese emergency event recognition model based on deep learning (CEERM). Firstly, we use a word segmentation system to segment sentences. According to event elements labeled in the CEC 2.0 corpus, we classify words into five categories: trigger words, participants, objects, time and location. Each word is vectorized according to the following six feature layers: part of speech, dependency grammar, length, location, distance between trigger word and core word and trigger word frequency. We obtain deep semantic features of words by training a feature vector set using a deep belief network (DBN), then analyze those features in order to identify trigger words by means of a back propagation neural network. Extensive testing shows that the CEERM achieves excellent recognition performance, with a maximum F-measure value of 85.17%. Moreover, we propose the dynamic-supervised DBN, which adds supervised fine-tuning to a restricted Boltzmann machine layer by monitoring its training performance. Test analysis reveals that the new DBN improves recognition performance and effectively controls the training time. Although the F-measure increases to 88.11%, the training time increases by only 25.35%. PMID:27501231

Event Recognition Based on Deep Learning in Chinese Texts.

PubMed

Zhang, Yajun; Liu, Zongtian; Zhou, Wen

2016-01-01

Event recognition is the most fundamental and critical task in event-based natural language processing systems. Existing event recognition methods based on rules and shallow neural networks have certain limitations. For example, extracting features using methods based on rules is difficult; methods based on shallow neural networks converge too quickly to a local minimum, resulting in low recognition precision. To address these problems, we propose the Chinese emergency event recognition model based on deep learning (CEERM). Firstly, we use a word segmentation system to segment sentences. According to event elements labeled in the CEC 2.0 corpus, we classify words into five categories: trigger words, participants, objects, time and location. Each word is vectorized according to the following six feature layers: part of speech, dependency grammar, length, location, distance between trigger word and core word and trigger word frequency. We obtain deep semantic features of words by training a feature vector set using a deep belief network (DBN), then analyze those features in order to identify trigger words by means of a back propagation neural network. Extensive testing shows that the CEERM achieves excellent recognition performance, with a maximum F-measure value of 85.17%. Moreover, we propose the dynamic-supervised DBN, which adds supervised fine-tuning to a restricted Boltzmann machine layer by monitoring its training performance. Test analysis reveals that the new DBN improves recognition performance and effectively controls the training time. Although the F-measure increases to 88.11%, the training time increases by only 25.35%.

From Memory to Attitude: The Neurocognitive Process beyond Euthanasia Acceptance.

PubMed

Enke, Martin; Meyer, Patric; Flor, Herta

2016-01-01

Numerous questionnaire studies on attitudes towards euthanasia produced conflicting results, precluding any general conclusion. This might be due to the fact that human behavior can be influenced by automatically triggered attitudes, which represent ingrained associations in memory and cannot be assessed by standard questionnaires, but require indirect measures such as reaction times (RT) or electroencephalographic recording (EEG). Event related potentials (ERPs) of the EEG and RT during an affective priming task were assessed to investigate the impact of automatically triggered attitudes and were compared to results of an explicit questionnaire. Explicit attitudes were ambivalent. Reaction time data showed neither positive nor negative associations towards euthanasia. ERP analyses revealed an N400 priming effect with lower mean amplitudes when euthanasia was associated with negative words. The euthanasia-related modulation of the N400 component shows an integration of the euthanasia object in negatively valenced associative neural networks. The integration of all measures suggests a bottom-up process of attitude activation, where automatically triggered negative euthanasia-relevant associations can become more ambiguous with increasing time in order to regulate the bias arising from automatic processes. These data suggest that implicit measures may make an important contribution to the understanding of euthanasia-related attitudes.

From Memory to Attitude: The Neurocognitive Process beyond Euthanasia Acceptance

PubMed Central

Enke, Martin; Meyer, Patric; Flor, Herta

2016-01-01

Numerous questionnaire studies on attitudes towards euthanasia produced conflicting results, precluding any general conclusion. This might be due to the fact that human behavior can be influenced by automatically triggered attitudes, which represent ingrained associations in memory and cannot be assessed by standard questionnaires, but require indirect measures such as reaction times (RT) or electroencephalographic recording (EEG). Event related potentials (ERPs) of the EEG and RT during an affective priming task were assessed to investigate the impact of automatically triggered attitudes and were compared to results of an explicit questionnaire. Explicit attitudes were ambivalent. Reaction time data showed neither positive nor negative associations towards euthanasia. ERP analyses revealed an N400 priming effect with lower mean amplitudes when euthanasia was associated with negative words. The euthanasia-related modulation of the N400 component shows an integration of the euthanasia object in negatively valenced associative neural networks. The integration of all measures suggests a bottom-up process of attitude activation, where automatically triggered negative euthanasia-relevant associations can become more ambiguous with increasing time in order to regulate the bias arising from automatic processes. These data suggest that implicit measures may make an important contribution to the understanding of euthanasia-related attitudes. PMID:27088244

Neural Control of the Lower Urinary Tract

PubMed Central

de Groat, William C.; Griffiths, Derek; Yoshimura, Naoki

2015-01-01

This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed. PMID:25589273

Human V4 Activity Patterns Predict Behavioral Performance in Imagery of Object Color.

PubMed

Bannert, Michael M; Bartels, Andreas

2018-04-11

Color is special among basic visual features in that it can form a defining part of objects that are engrained in our memory. Whereas most neuroimaging research on human color vision has focused on responses related to external stimulation, the present study investigated how sensory-driven color vision is linked to subjective color perception induced by object imagery. We recorded fMRI activity in male and female volunteers during viewing of abstract color stimuli that were red, green, or yellow in half of the runs. In the other half we asked them to produce mental images of colored, meaningful objects (such as tomato, grapes, banana) corresponding to the same three color categories. Although physically presented color could be decoded from all retinotopically mapped visual areas, only hV4 allowed predicting colors of imagined objects when classifiers were trained on responses to physical colors. Importantly, only neural signal in hV4 was predictive of behavioral performance in the color judgment task on a trial-by-trial basis. The commonality between neural representations of sensory-driven and imagined object color and the behavioral link to neural representations in hV4 identifies area hV4 as a perceptual hub linking externally triggered color vision with color in self-generated object imagery. SIGNIFICANCE STATEMENT Humans experience color not only when visually exploring the outside world, but also in the absence of visual input, for example when remembering, dreaming, and during imagery. It is not known where neural codes for sensory-driven and internally generated hue converge. In the current study we evoked matching subjective color percepts, one driven by physically presented color stimuli, the other by internally generated color imagery. This allowed us to identify area hV4 as the only site where neural codes of corresponding subjective color perception converged regardless of its origin. Color codes in hV4 also predicted behavioral performance in an imagery task, suggesting it forms a perceptual hub for color perception. Copyright © 2018 the authors 0270-6474/18/383657-12$15.00/0.

Analysis of feature selection with Probabilistic Neural Network (PNN) to classify sources influencing indoor air quality

NASA Astrophysics Data System (ADS)

Saad, S. M.; Shakaff, A. Y. M.; Saad, A. R. M.; Yusof, A. M.; Andrew, A. M.; Zakaria, A.; Adom, A. H.

2017-03-01

There are various sources influencing indoor air quality (IAQ) which could emit dangerous gases such as carbon monoxide (CO), carbon dioxide (CO2), ozone (O3) and particulate matter. These gases are usually safe for us to breathe in if they are emitted in safe quantity but if the amount of these gases exceeded the safe level, they might be hazardous to human being especially children and people with asthmatic problem. Therefore, a smart indoor air quality monitoring system (IAQMS) is needed that able to tell the occupants about which sources that trigger the indoor air pollution. In this project, an IAQMS that able to classify sources influencing IAQ has been developed. This IAQMS applies a classification method based on Probabilistic Neural Network (PNN). It is used to classify the sources of indoor air pollution based on five conditions: ambient air, human activity, presence of chemical products, presence of food and beverage, and presence of fragrance. In order to get good and best classification accuracy, an analysis of several feature selection based on data pre-processing method is done to discriminate among the sources. The output from each data pre-processing method has been used as the input for the neural network. The result shows that PNN analysis with the data pre-processing method give good classification accuracy of 99.89% and able to classify the sources influencing IAQ high classification rate.

Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats.

PubMed

Johnson, Paul M; Kenny, Paul J

2010-05-01

We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.

Putting the brain to work: neuroergonomics past, present, and future.

PubMed

Parasuraman, Raja; Wilson, Glenn F

2008-06-01

The authors describe research and applications in prominent areas of neuroergonomics. Because human factors/ergonomics examines behavior and mind at work, it should include the study of brain mechanisms underlying human performance. Neuroergonomic studies are reviewed in four areas: workload and vigilance, adaptive automation, neuroengineering, and molecular genetics and individual differences. Neuroimaging studies have helped identify the components of mental workload, workload assessment in complex tasks, and resource depletion in vigilance. Furthermore, real-time neurocognitive assessment of workload can trigger adaptive automation. Neural measures can also drive brain-computer interfaces to provide disabled users new communication channels. Finally, variants of particular genes can be associated with individual differences in specific cognitive functions. Neuroergonomics shows that considering what makes work possible - the human brain - can enrich understanding of the use of technology by humans and can inform technological design. Applications of neuroergonomics include the assessment of operator workload and vigilance, implementation of real-time adaptive automation, neuroengineering for people with disabilities, and design of selection and training methods.

Genetic determinants of aggression and impulsivity in humans.

PubMed

Pavlov, Konstantin A; Chistiakov, Dimitry A; Chekhonin, Vladimir P

2012-02-01

Human aggression/impulsivity-related traits have a complex background that is greatly influenced by genetic and non-genetic factors. The relationship between aggression and anxiety is regulated by highly conserved brain regions including amygdala, which controls neural circuits triggering defensive, aggressive, or avoidant behavioral models. The dysfunction of neural circuits responsible for emotional control was shown to represent an etiological factor of violent behavior. In addition to the amygdala, these circuits also involve the anterior cingulated cortex and regions of the prefrontal cortex. Excessive reactivity in the amygdala coupled with inadequate prefrontal regulation serves to increase the likelihood of aggressive behavior. Developmental alterations in prefrontal-subcortical circuitry as well as neuromodulatory and hormonal abnormality appear to play a role. Imbalance in testosterone/serotonin and testosterone/cortisol ratios (e.g., increased testosterone levels and reduced cortisol levels) increases the propensity toward aggression because of reduced activation of the neural circuitry of impulse control and self-regulation. Serotonin facilitates prefrontal inhibition, and thus insufficient serotonergic activity can enhance aggression. Genetic predisposition to aggression appears to be deeply affected by the polymorphic genetic variants of the serotoninergic system that influences serotonin levels in the central and peripheral nervous system, biological effects of this hormone, and rate of serotonin production, synaptic release and degradation. Among these variants, functional polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) may be of particular importance due to the relationship between these polymorphic variants and anatomical changes in the limbic system of aggressive people. Furthermore, functional variants of MAOA and 5-HTT are capable of mediating the influence of environmental factors on aggression-related traits. In this review, we consider genetic determinants of human aggression, with special emphasis on genes involved in serotonin and dopamine metabolism and function.

Early neural disruption and auditory processing outcomes in rodent models: implications for developmental language disability

PubMed Central

Fitch, R. Holly; Alexander, Michelle L.; Threlkeld, Steven W.

2013-01-01

Most researchers in the field of neural plasticity are familiar with the “Kennard Principle,” which purports a positive relationship between age at brain injury and severity of subsequent deficits (plateauing in adulthood). As an example, a child with left hemispherectomy can recover seemingly normal language, while an adult with focal injury to sub-regions of left temporal and/or frontal cortex can suffer dramatic and permanent language loss. Here we present data regarding the impact of early brain injury in rat models as a function of type and timing, measuring long-term behavioral outcomes via auditory discrimination tasks varying in temporal demand. These tasks were created to model (in rodents) aspects of human sensory processing that may correlate—both developmentally and functionally—with typical and atypical language. We found that bilateral focal lesions to the cortical plate in rats during active neuronal migration led to worse auditory outcomes than comparable lesions induced after cortical migration was complete. Conversely, unilateral hypoxic-ischemic (HI) injuries (similar to those seen in premature infants and term infants with birth complications) led to permanent auditory processing deficits when induced at a neurodevelopmental point comparable to human “term,” but only transient deficits (undetectable in adulthood) when induced in a “preterm” window. Convergent evidence suggests that regardless of when or how disruption of early neural development occurs, the consequences may be particularly deleterious to rapid auditory processing (RAP) outcomes when they trigger developmental alterations that extend into subcortical structures (i.e., lower sensory processing stations). Collective findings hold implications for the study of behavioral outcomes following early brain injury as well as genetic/environmental disruption, and are relevant to our understanding of the neurologic risk factors underlying developmental language disability in human populations. PMID:24155699

Specification of functional cranial placode derivatives from human pluripotent stem cells.

PubMed

Dincer, Zehra; Piao, Jinghua; Niu, Lei; Ganat, Yosif; Kriks, Sonja; Zimmer, Bastian; Shi, Song-Hai; Tabar, Viviane; Studer, Lorenz

2013-12-12

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. Human placode development has remained largely inaccessible despite the serious medical conditions caused by the dysfunction of placode-derived tissues. Here, we demonstrate the efficient derivation of cranial placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Concomitant inhibition of fibroblast growth factor signaling disrupts placode derivation and induces surface ectoderm. Further fate specification at the preplacode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers, and anterior pituitary hormone-producing cells that upon transplantation produce human growth hormone and adrenocorticotropic hormone in vivo. Our results establish a powerful experimental platform to study human cranial placode development and set the stage for the development of human cell-based therapies in sensory and endocrine disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Quantitative Analyses of Synergistic Responses between Cannabidiol and DNA-Damaging Agents on the Proliferation and Viability of Glioblastoma and Neural Progenitor Cells in Culture

PubMed Central

Deng, Liting; Ng, Lindsay; Ozawa, Tatsuya

2017-01-01

Evidence suggests that the nonpsychotropic cannabis-derived compound, cannabidiol (CBD), has antineoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the antiproliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine, or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures. This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system toxicity. We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells. Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells. Cotreatment regimens combining CBD and DNA-damaging agents produced synergistic antiproliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs. Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells. Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little to no therapeutic window when considering NPCs. PMID:27821713

Models of Acetylcholine and Dopamine Signals Differentially Improve Neural Representations

PubMed Central

Holca-Lamarre, Raphaël; Lücke, Jörg; Obermayer, Klaus

2017-01-01

Biological and artificial neural networks (ANNs) represent input signals as patterns of neural activity. In biology, neuromodulators can trigger important reorganizations of these neural representations. For instance, pairing a stimulus with the release of either acetylcholine (ACh) or dopamine (DA) evokes long lasting increases in the responses of neurons to the paired stimulus. The functional roles of ACh and DA in rearranging representations remain largely unknown. Here, we address this question using a Hebbian-learning neural network model. Our aim is both to gain a functional understanding of ACh and DA transmission in shaping biological representations and to explore neuromodulator-inspired learning rules for ANNs. We model the effects of ACh and DA on synaptic plasticity and confirm that stimuli coinciding with greater neuromodulator activation are over represented in the network. We then simulate the physiological release schedules of ACh and DA. We measure the impact of neuromodulator release on the network's representation and on its performance on a classification task. We find that ACh and DA trigger distinct changes in neural representations that both improve performance. The putative ACh signal redistributes neural preferences so that more neurons encode stimulus classes that are challenging for the network. The putative DA signal adapts synaptic weights so that they better match the classes of the task at hand. Our model thus offers a functional explanation for the effects of ACh and DA on cortical representations. Additionally, our learning algorithm yields performances comparable to those of state-of-the-art optimisation methods in multi-layer perceptrons while requiring weaker supervision signals and interacting with synaptically-local weight updates. PMID:28690509

Design of robust reliable control for T-S fuzzy Markovian jumping delayed neutral type neural networks with probabilistic actuator faults and leakage delays: An event-triggered communication scheme.

PubMed

Syed Ali, M; Vadivel, R; Saravanakumar, R

2018-06-01

This study examines the problem of robust reliable control for Takagi-Sugeno (T-S) fuzzy Markovian jumping delayed neural networks with probabilistic actuator faults and leakage terms. An event-triggered communication scheme. First, the randomly occurring actuator faults and their failures rates are governed by two sets of unrelated random variables satisfying certain probabilistic failures of every actuator, new type of distribution based event triggered fault model is proposed, which utilize the effect of transmission delay. Second, Takagi-Sugeno (T-S) fuzzy model is adopted for the neural networks and the randomness of actuators failures is modeled in a Markov jump model framework. Third, to guarantee the considered closed-loop system is exponential mean square stable with a prescribed reliable control performance, a Markov jump event-triggered scheme is designed in this paper, which is the main purpose of our study. Fourth, by constructing appropriate Lyapunov-Krasovskii functional, employing Newton-Leibniz formulation and integral inequalities, several delay-dependent criteria for the solvability of the addressed problem are derived. The obtained stability criteria are stated in terms of linear matrix inequalities (LMIs), which can be checked numerically using the effective LMI toolbox in MATLAB. Finally, numerical examples are given to illustrate the effectiveness and reduced conservatism of the proposed results over the existing ones, among them one example was supported by real-life application of the benchmark problem. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Changes in neural network homeostasis trigger neuropsychiatric symptoms.

PubMed

Winkelmann, Aline; Maggio, Nicola; Eller, Joanna; Caliskan, Gürsel; Semtner, Marcus; Häussler, Ute; Jüttner, René; Dugladze, Tamar; Smolinsky, Birthe; Kowalczyk, Sarah; Chronowska, Ewa; Schwarz, Günter; Rathjen, Fritz G; Rechavi, Gideon; Haas, Carola A; Kulik, Akos; Gloveli, Tengis; Heinemann, Uwe; Meier, Jochen C

2014-02-01

The mechanisms that regulate the strength of synaptic transmission and intrinsic neuronal excitability are well characterized; however, the mechanisms that promote disease-causing neural network dysfunction are poorly defined. We generated mice with targeted neuron type-specific expression of a gain-of-function variant of the neurotransmitter receptor for glycine (GlyR) that is found in hippocampectomies from patients with temporal lobe epilepsy. In this mouse model, targeted expression of gain-of-function GlyR in terminals of glutamatergic cells or in parvalbumin-positive interneurons persistently altered neural network excitability. The increased network excitability associated with gain-of-function GlyR expression in glutamatergic neurons resulted in recurrent epileptiform discharge, which provoked cognitive dysfunction and memory deficits without affecting bidirectional synaptic plasticity. In contrast, decreased network excitability due to gain-of-function GlyR expression in parvalbumin-positive interneurons resulted in an anxiety phenotype, but did not affect cognitive performance or discriminative associative memory. Our animal model unveils neuron type-specific effects on cognition, formation of discriminative associative memory, and emotional behavior in vivo. Furthermore, our data identify a presynaptic disease-causing molecular mechanism that impairs homeostatic regulation of neural network excitability and triggers neuropsychiatric symptoms.

Cdk1 Activates Pre-mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem Cells.

PubMed

Baffet, Alexandre D; Hu, Daniel J; Vallee, Richard B

2015-06-22

Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2 via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell-cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell-cycle regulated and identify the trigger mechanism for apical nuclear migration in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Remote radio control of insect flight.

PubMed

Sato, Hirotaka; Berry, Christopher W; Peeri, Yoav; Baghoomian, Emen; Casey, Brendan E; Lavella, Gabriel; Vandenbrooks, John M; Harrison, Jon F; Maharbiz, Michel M

2009-01-01

We demonstrated the remote control of insects in free flight via an implantable radio-equipped miniature neural stimulating system. The pronotum mounted system consisted of neural stimulators, muscular stimulators, a radio transceiver-equipped microcontroller and a microbattery. Flight initiation, cessation and elevation control were accomplished through neural stimulus of the brain which elicited, suppressed or modulated wing oscillation. Turns were triggered through the direct muscular stimulus of either of the basalar muscles. We characterized the response times, success rates, and free-flight trajectories elicited by our neural control systems in remotely controlled beetles. We believe this type of technology will open the door to in-flight perturbation and recording of insect flight responses.

Spatiotemporal commonalities of fronto-parietal activation in attentional orienting triggered by supraliminal and subliminal gaze cues: An event-related potential study.

PubMed

Uono, Shota; Sato, Wataru; Sawada, Reiko; Kochiyama, Takanori; Toichi, Motomi

2018-05-04

Eye gaze triggers attentional shifts with and without conscious awareness. It remains unclear whether the spatiotemporal patterns of electric neural activity are the same for conscious and unconscious attentional shifts. Thus, the present study recorded event-related potentials (ERPs) and evaluated the neural activation involved in attentional orienting induced by subliminal and supraliminal gaze cues. Nonpredictive gaze cues were presented in the central field of vision, and participants were asked to detect a subsequent peripheral target. The mean reaction time was shorter for congruent gaze cues than for incongruent gaze cues under both presentation conditions, indicating that both types of cues reliably trigger attentional orienting. The ERP analysis revealed that averted versus straight gaze induced greater negative deflection in the bilateral fronto-central and temporal regions between 278 and 344 ms under both supraliminal and subliminal presentation conditions. Supraliminal cues, irrespective of gaze direction, induced a greater negative amplitude than did subliminal cues at the right posterior cortices at a peak of approximately 170 ms and in the 200-300 ms. These results suggest that similar spatial and temporal fronto-parietal activity is involved in attentional orienting triggered by both supraliminal and subliminal gaze cues, although inputs from different visual processing routes (cortical and subcortical regions) may trigger activity in the attentional network. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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.

Cocaine action on peripheral, non-monoamine neural substrates as a trigger of EEG desynchronization and EMG activation following intravenous administration in freely moving rats

PubMed Central

Smirnov, Michael S.; Kiyatkin, Eugene A.

2009-01-01

Many important physiological, behavioral and subjective effects of intravenous (iv) cocaine (COC) are exceptionally rapid and transient, suggesting a possible involvement of peripheral neural substrates in their triggering. In the present study, we used high-speed EEG and EMG recordings (4-s resolution) in freely moving rats to characterize the central electrophysiological effects of iv COC at low doses within a self-administration range (0.25-1.0 mg/kg). We found that COC induces rapid, strong, and prolonged desynchronization of cortical EEG (decrease in alpha and increase in beta and gamma activity) and activation of the neck EMG that begin within 2-6 s following the start of a 10-s injection; immediate components of both effects were dose-independent. The rapid effects of COC were mimicked by iv COC methiodide, a derivative that cannot cross the blood-brain barrier. At equimolar doses (0.33-1.33 mg/kg), COC methiodide had equally fast and strong effects on EEG and EMG total powers, decreasing alpha and increasing beta and gamma activities. Rapid EEG desynchronization and EMG activation was also induced by iv procaine, a structurally similar, short-acting local anesthetic with virtually no effects on monoamine uptake; at equipotential doses (1.25-5.0 mg/kg), these effects were weaker and shorter in duration than those of COC. Surprisingly, iv saline injection delivered during slow-wave sleep (but not during quiet wakefulness) also induced a transient EEG desynchronization but without changes in EMG and motor activity; these effects were significantly weaker and much shorter than those induced by all tested drugs. These data suggest that in awake animals, iv COC induces rapid cortical activation and a subsequent motor response via its action on peripheral non-monoamine neural elements, involving neural transmission via visceral sensory pathways. By providing a rapid neural signal and triggering neural activation, such an action might play a crucial role in the sensory effects of COC, thus contributing to the learning and development of drug-taking behavior. PMID:19861149

Cocaine action on peripheral, non-monoamine neural substrates as a trigger of electroencephalographic desynchronization and electromyographic activation following i.v. administration in freely moving rats.

PubMed

Smirnov, M S; Kiyatkin, E A

2010-01-20

Many important physiological, behavioral and subjective effects of i.v. cocaine (COC) are exceptionally rapid and transient, suggesting a possible involvement of peripheral neural substrates in their triggering. In the present study, we used high-speed electroencephalographic (EEG) and electromyographic (EMG) recordings (4-s resolution) in freely moving rats to characterize the central electrophysiological effects of i.v. COC at low doses within a self-administration range (0.25-1.0 mg/kg). We found that COC induces rapid, strong, and prolonged desynchronization of cortical EEG (decrease in alpha and increase in beta and gamma activity) and activation of the neck EMG that begin within 2-6 s following the start of a 10-s injection; immediate components of both effects were dose-independent. The rapid effects of COC were mimicked by i.v. COC methiodide (COC-MET), a derivative that cannot cross the blood-brain barrier. At equimolar doses (0.33-1.33 mg/kg), COC-MET had equally fast and strong effects on EEG and EMG total powers, decreasing alpha and increasing beta and gamma activities. Rapid EEG desynchronization and EMG activation was also induced by i.v. procaine, a structurally similar, short-acting local anesthetic with virtually no effects on monoamine uptake; at equipotential doses (1.25-5.0 mg/kg), these effects were weaker and shorter in duration than those of COC. Surprisingly, i.v. saline injection delivered during slow-wave sleep (but not during quiet wakefulness) also induced a transient EEG desynchronization but without changes in EMG and motor activity; these effects were significantly weaker and much shorter than those induced by all tested drugs. These data suggest that in awake animals, i.v. COC induces rapid cortical activation and a subsequent motor response via its action on peripheral non-monoamine neural elements, involving neural transmission via visceral sensory pathways. By providing a rapid neural signal and triggering neural activation, such an action might play a crucial role in the sensory effects of COC, thus contributing to the learning and development of drug-taking behavior.

“We make choices we think are going to save us”: Debate and stance identification for online breast cancer CAM discussions

PubMed Central

Zhang, Shaodian; Qiu, Lin; Chen, Frank; Zhang, Weinan; Yu, Yong; Elhadad, Noémie

2017-01-01

Patients discuss complementary and alternative medicine (CAM) in online health communities. Sometimes, patients’ conflicting opinions toward CAM-related issues trigger debates in the community. The objectives of this paper are to identify such debates, identify controversial CAM therapies in a popular online breast cancer community, as well as patients’ stances towards them. To scale our analysis, we trained a set of classifiers. We first constructed a supervised classifier based on a long short-term memory neural network (LSTM) stacked over a convolutional neural network (CNN) to detect automatically CAM-related debates from a popular breast cancer forum. Members’ stances in these debates were also identified by a CNN-based classifier. Finally, posts automatically flagged as debates by the classifier were analyzed to explore which specific CAM therapies trigger debates more often than others. Our methods are able to detect CAM debates with F score of 77%, and identify stances with F score of 70%. The debate classifier identified about 1/6 of all CAM-related posts as debate. About 60% of CAM-related debate posts represent the supportive stance toward CAM usage. Qualitative analysis shows that some specific therapies, such as Gerson therapy and usage of laetrile, trigger debates frequently among members of the breast cancer community. This study demonstrates that neural networks can effectively locate debates on usage and effectiveness of controversial CAM therapies, and can help make sense of patients’ opinions on such issues under dispute. As to CAM for breast cancer, perceptions of their effectiveness vary among patients. Many of the specific therapies trigger debates frequently and are worth more exploration in future work. PMID:28967000

"We make choices we think are going to save us": Debate and stance identification for online breast cancer CAM discussions.

PubMed

Zhang, Shaodian; Qiu, Lin; Chen, Frank; Zhang, Weinan; Yu, Yong; Elhadad, Noémie

2017-04-01

Patients discuss complementary and alternative medicine (CAM) in online health communities. Sometimes, patients' conflicting opinions toward CAM-related issues trigger debates in the community. The objectives of this paper are to identify such debates, identify controversial CAM therapies in a popular online breast cancer community, as well as patients' stances towards them. To scale our analysis, we trained a set of classifiers. We first constructed a supervised classifier based on a long short-term memory neural network (LSTM) stacked over a convolutional neural network (CNN) to detect automatically CAM-related debates from a popular breast cancer forum. Members' stances in these debates were also identified by a CNN-based classifier. Finally, posts automatically flagged as debates by the classifier were analyzed to explore which specific CAM therapies trigger debates more often than others. Our methods are able to detect CAM debates with F score of 77%, and identify stances with F score of 70%. The debate classifier identified about 1/6 of all CAM-related posts as debate. About 60% of CAM-related debate posts represent the supportive stance toward CAM usage. Qualitative analysis shows that some specific therapies, such as Gerson therapy and usage of laetrile, trigger debates frequently among members of the breast cancer community. This study demonstrates that neural networks can effectively locate debates on usage and effectiveness of controversial CAM therapies, and can help make sense of patients' opinions on such issues under dispute. As to CAM for breast cancer, perceptions of their effectiveness vary among patients. Many of the specific therapies trigger debates frequently and are worth more exploration in future work.

Remote modulation of neural activities via near-infrared triggered release of biomolecules.

PubMed

Li, Wei; Luo, Rongcong; Lin, Xudong; Jadhav, Amol D; Zhang, Zicong; Yan, Li; Chan, Chung-Yuan; Chen, Xianfeng; He, Jufang; Chen, Chia-Hung; Shi, Peng

2015-10-01

The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically-controlled delivery technology a general and important tool in cell biology research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing.

PubMed

Olivares, Ela I; Lage-Castellanos, Agustín; Bobes, María A; Iglesias, Jaime

2018-01-01

We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs) in both intra-domain (face-feature) and cross-domain (face-occupation) matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called "Fusiform Face Area", "FFA" and "Occipital Face Area", "OFA", respectively), the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands.

Facilitated early cortical processing of nude human bodies.

PubMed

Alho, Jussi; Salminen, Nelli; Sams, Mikko; Hietanen, Jari K; Nummenmaa, Lauri

2015-07-01

Functional brain imaging has identified specialized neural systems supporting human body perception. Responses to nude vs. clothed bodies within this system are amplified. However, it remains unresolved whether nude and clothed bodies are processed by same cerebral networks or whether processing of nude bodies recruits additional affective and arousal processing areas. We recorded simultaneous MEG and EEG while participants viewed photographs of clothed and nude bodies. Global field power revealed a peak ∼145ms after stimulus onset to both clothed and nude bodies, and ∼205ms exclusively to nude bodies. Nude-body-sensitive responses were centered first (100-200ms) in the extrastriate and fusiform body areas, and subsequently (200-300ms) in affective-motivational areas including insula and anterior cingulate cortex. We conclude that visibility of sexual features facilitates early cortical processing of human bodies, the purpose of which is presumably to trigger sexual behavior and ultimately ensure reproduction. Copyright © 2015 Elsevier B.V. All rights reserved.

Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes.

PubMed

Hawkins, Simon J; Crompton, Lucy A; Sood, Aman; Saunders, Margaret; Boyle, Noreen T; Buckley, Amy; Minogue, Aedín M; McComish, Sarah F; Jiménez-Moreno, Natalia; Cordero-Llana, Oscar; Stathakos, Petros; Gilmore, Catherine E; Kelly, Stephen; Lane, Jon D; Case, C Patrick; Caldwell, Maeve A

2018-05-01

The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes. Crucially, neuronal DNA damage is mediated by astrocytes. Inhibiting the autophagic degradation in the BeWo barrier by overexpression of the dominant-negative human ATG4B C74A significantly reduces the levels of DNA damage in astrocytes. In vivo, indirect NP toxicity in mice results in neurodevelopmental abnormalities with reactive astrogliosis and increased DNA damage in the fetal hippocampus. Our results demonstrate the potential importance of autophagy to elicit NP toxicity and the risk of indirect developmental neurotoxicity after maternal NP exposure.

Using Human iPSC-Derived Neurons to Model TAU Aggregation

PubMed Central

Verheyen, An; Diels, Annick; Dijkmans, Joyce; Oyelami, Tutu; Meneghello, Giulia; Mertens, Liesbeth; Versweyveld, Sofie; Borgers, Marianne; Buist, Arjan; Peeters, Pieter; Cik, Miroslav

2015-01-01

Alzheimer’s disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-aggregating P301L mutation into control hiPSC-derived neural progenitor cells followed by differentiation into cortical neurons. TAU aggregation and phosphorylation was quantified using AlphaLISA technology. Although no spontaneous aggregation was observed upon expressing TAU-P301L in neurons, seeding with preformed aggregates consisting of the TAU-microtubule binding repeat domain triggered robust TAU aggregation and hyperphosphorylation already after 2 weeks, without affecting general cell health. To validate our model, activity of two autophagy inducers was tested. Both rapamycin and trehalose significantly reduced TAU aggregation levels suggesting that iPSC-derived neurons allow for the generation of a biologically relevant human Tauopathy model, highly suitable to screen for compounds that modulate TAU aggregation. PMID:26720731

Nanoparticle-induced neuronal toxicity across placental barriers is mediated by autophagy and dependent on astrocytes

NASA Astrophysics Data System (ADS)

Hawkins, Simon J.; Crompton, Lucy A.; Sood, Aman; Saunders, Margaret; Boyle, Noreen T.; Buckley, Amy; Minogue, Aedín M.; McComish, Sarah F.; Jiménez-Moreno, Natalia; Cordero-Llana, Oscar; Stathakos, Petros; Gilmore, Catherine E.; Kelly, Stephen; Lane, Jon D.; Case, C. Patrick; Caldwell, Maeve A.

2018-05-01

The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes. Crucially, neuronal DNA damage is mediated by astrocytes. Inhibiting the autophagic degradation in the BeWo barrier by overexpression of the dominant-negative human ATG4BC74A significantly reduces the levels of DNA damage in astrocytes. In vivo, indirect NP toxicity in mice results in neurodevelopmental abnormalities with reactive astrogliosis and increased DNA damage in the fetal hippocampus. Our results demonstrate the potential importance of autophagy to elicit NP toxicity and the risk of indirect developmental neurotoxicity after maternal NP exposure.

Adaptive Neural Network-Based Event-Triggered Control of Single-Input Single-Output Nonlinear Discrete-Time Systems.

PubMed

Sahoo, Avimanyu; Xu, Hao; Jagannathan, Sarangapani

2016-01-01

This paper presents a novel adaptive neural network (NN) control of single-input and single-output uncertain nonlinear discrete-time systems under event sampled NN inputs. In this control scheme, the feedback signals are transmitted, and the NN weights are tuned in an aperiodic manner at the event sampled instants. After reviewing the NN approximation property with event sampled inputs, an adaptive state estimator (SE), consisting of linearly parameterized NNs, is utilized to approximate the unknown system dynamics in an event sampled context. The SE is viewed as a model and its approximated dynamics and the state vector, during any two events, are utilized for the event-triggered controller design. An adaptive event-trigger condition is derived by using both the estimated NN weights and a dead-zone operator to determine the event sampling instants. This condition both facilitates the NN approximation and reduces the transmission of feedback signals. The ultimate boundedness of both the NN weight estimation error and the system state vector is demonstrated through the Lyapunov approach. As expected, during an initial online learning phase, events are observed more frequently. Over time with the convergence of the NN weights, the inter-event times increase, thereby lowering the number of triggered events. These claims are illustrated through the simulation results.

A model of cerebrocerebello-spinomuscular interaction in the sagittal control of human walking.

PubMed

Jo, Sungho; Massaquoi, Steve G

2007-03-01

A computationally developed model of human upright balance control (Jo and Massaquoi on Biol cybern 91:188-202, 2004) has been enhanced to describe biped walking in the sagittal plane. The model incorporates (a) non-linear muscle mechanics having activation level -dependent impedance, (b) scheduled cerebrocerebellar interaction for control of center of mass position and trunk pitch angle, (c) rectangular pulse-like feedforward commands from a brainstem/ spinal pattern generator, and (d) segmental reflex modulation of muscular synergies to refine inter-joint coordination. The model can stand when muscles around the ankle are coactivated. When trigger signals activate, the model transitions from standing still to walking at 1.5 m/s. Simulated natural walking displays none of seven pathological gait features. The model can simulate different walking speeds by tuning the amplitude and frequency in spinal pattern generator. The walking is stable against forward and backward pushes of up to 70 and 75 N, respectively, and with sudden changes in trunk mass of up to 18%. The sensitivity of the model to changes in neural parameters and the predicted behavioral results of simulated neural system lesions are examined. The deficit gait simulations may be useful to support the functional and anatomical correspondences of the model. The model demonstrates that basic human-like walking can be achieved by a hierarchical structure of stabilized-long loop feedback and synergy-mediated feedforward controls. In particular, internal models of body dynamics are not required.

Quantitative Analyses of Synergistic Responses between Cannabidiol and DNA-Damaging Agents on the Proliferation and Viability of Glioblastoma and Neural Progenitor Cells in Culture.

PubMed

Deng, Liting; Ng, Lindsay; Ozawa, Tatsuya; Stella, Nephi

2017-01-01

Evidence suggests that the nonpsychotropic cannabis-derived compound, cannabidiol (CBD), has antineoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the antiproliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine, or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures. This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system toxicity. We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells. Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells. Cotreatment regimens combining CBD and DNA-damaging agents produced synergistic antiproliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs. Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells. Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little to no therapeutic window when considering NPCs. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

An optimization of the FPGA trigger based on the artificial neural network for a detection of neutrino-origin showers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szadkowski, Zbigniew; Glas, Dariusz; Pytel, Krzysztof

Observations of ultra-high energy neutrinos became a priority in experimental astro-particle physics. Up to now, the Pierre Auger Observatory did not find any candidate on a neutrino event. This imposes competitive limits to the diffuse flux of ultra-high energy neutrinos in the EeV range and above. A very low rate of events potentially generated by neutrinos is a significant challenge for a detection technique and requires both sophisticated algorithms and high-resolution hardware. A trigger based on a artificial neural network was implemented into the Cyclone{sup R} V E FPGA 5CEFA9F31I7. The prototype Front-End boards for Auger-Beyond-2015 with Cyclone{sup R} Vmore » E can test the neural network algorithm in real pampas conditions in 2015. Showers for muon and tau neutrino initiating particles on various altitudes, angles and energies were simulated in CORSICA and Offline platforms giving pattern of ADC traces in Auger water Cherenkov detectors. The 3-layer 12-10-1 neural network was taught in MATLAB by simulated ADC traces according the Levenberg-Marquardt algorithm. Results show that a probability of a ADC traces generation is very low due to a small neutrino cross-section. Nevertheless, ADC traces, if occur, for 1-10 EeV showers are relatively short and can be analyzed by 16-point input algorithm. For 100 EeV range traces are much longer, but with significantly higher amplitudes, which can be detected by standard threshold algorithms. We optimized the coefficients from MATLAB to get a maximal range of potentially registered events and for fixed-point FPGA processing to minimize calculation errors. Currently used Front-End boards based on no-more produced ACEXR PLDs and obsolete Cyclone{sup R} FPGAs allow an implementation of relatively simple threshold algorithms for triggers. New sophisticated trigger implemented in Cyclone{sup R} V E FPGAs with large amount of DSP blocks, embedded memory running with 120 - 160 MHz sampling may support to discover neutrino events in the Pierre Auger Observatory. (authors)« less

Briefly Cuing Memories Leads to Suppression of Their Neural Representations

PubMed Central

Norman, Kenneth A.

2014-01-01

Previous studies have linked partial memory activation with impaired subsequent memory retrieval (e.g., Detre et al., 2013) but have not provided an account of this phenomenon at the level of memory representations: How does partial activation change the neural pattern subsequently elicited when the memory is cued? To address this question, we conducted a functional magnetic resonance imaging (fMRI) experiment in which participants studied word-scene paired associates. Later, we weakly reactivated some memories by briefly presenting the cue word during a rapid serial visual presentation (RSVP) task; other memories were more strongly reactivated or not reactivated at all. We tested participants' memory for the paired associates before and after RSVP. Cues that were briefly presented during RSVP triggered reduced levels of scene activity on the post-RSVP memory test, relative to the other conditions. We used pattern similarity analysis to assess how representations changed as a function of the RSVP manipulation. For briefly cued pairs, we found that neural patterns elicited by the same cue on the pre- and post-RSVP tests (preA–postA; preB–postB) were less similar than neural patterns elicited by different cues (preA–postB; preB–postA). These similarity reductions were predicted by neural measures of memory activation during RSVP. Through simulation, we show that our pattern similarity results are consistent with a model in which partial memory activation triggers selective weakening of the strongest parts of the memory. PMID:24899722

Differential Left Hippocampal Activation during Retrieval with Different Types of Reminders: An fMRI Study of the Reconsolidation Process

PubMed Central

De Pino, Gabriela; Fernández, Rodrigo Sebastián; Villarreal, Mirta Fabiana; Pedreira, María Eugenia

2016-01-01

Consolidated memories return to a labile state after the presentation of cues (reminders) associated with acquisition, followed by a period of stabilization (reconsolidation). However not all cues are equally effective in initiating the process, unpredictable cues triggered it, predictable cues do not. We hypothesize that the different effects observed by the different reminder types on memory labilization-reconsolidation depend on a differential neural involvement during reminder presentation. To test it, we developed a declarative task and compared the efficacy of three reminder types in triggering the process in humans (Experiment 1). Finally, we compared the brain activation patterns between the different conditions using functional magnetic resonance imaging (fMRI) (Experiment 2). We confirmed that the unpredictable reminder is the most effective in initiating the labilization-reconsolidation process. Furthermore, only under this condition there was differential left hippocampal activation during its presentation. We suggest that the left hippocampus is detecting the incongruence between actual and past events and allows the memory to be updated. PMID:26991776

Roles for Arc in metabotropic glutamate receptor-dependent LTD and synapse elimination: Implications in health and disease.

PubMed

Wilkerson, Julia R; Albanesi, Joseph P; Huber, Kimberly M

2018-05-01

The Arc gene is robustly transcribed in specific neural ensembles in response to experience-driven activity. Upon induction, Arc mRNA is transported to dendrites, where it can be rapidly and locally translated by activation of metabotropic glutamate receptors (mGluR1/5). mGluR-induced dendritic synthesis of Arc is implicated in weakening or elimination of excitatory synapses by triggering endocytosis of postsynaptic AMPARs in both hippocampal CA1 and cerebellar Purkinje neurons. Importantly, CA1 neurons with experience-induced Arc mRNA are susceptible, or primed for mGluR-induced long-term synaptic depression (mGluR-LTD). Here we review mechanisms and function of Arc in mGluR-LTD and synapse elimination and propose roles for these forms of plasticity in Arc-dependent formation of sparse neural representations of learned experience. We also discuss accumulating evidence linking dysregulation of Arc and mGluR-LTD in human cognitive disorders such as intellectual disability, autism and Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spike avalanches in vivo suggest a driven, slightly subcritical brain state

PubMed Central

Priesemann, Viola; Wibral, Michael; Valderrama, Mario; Pröpper, Robert; Le Van Quyen, Michel; Geisel, Theo; Triesch, Jochen; Nikolić, Danko; Munk, Matthias H. J.

2014-01-01

In self-organized critical (SOC) systems avalanche size distributions follow power-laws. Power-laws have also been observed for neural activity, and so it has been proposed that SOC underlies brain organization as well. Surprisingly, for spiking activity in vivo, evidence for SOC is still lacking. Therefore, we analyzed highly parallel spike recordings from awake rats and monkeys, anesthetized cats, and also local field potentials from humans. We compared these to spiking activity from two established critical models: the Bak-Tang-Wiesenfeld model, and a stochastic branching model. We found fundamental differences between the neural and the model activity. These differences could be overcome for both models through a combination of three modifications: (1) subsampling, (2) increasing the input to the model (this way eliminating the separation of time scales, which is fundamental to SOC and its avalanche definition), and (3) making the model slightly sub-critical. The match between the neural activity and the modified models held not only for the classical avalanche size distributions and estimated branching parameters, but also for two novel measures (mean avalanche size, and frequency of single spikes), and for the dependence of all these measures on the temporal bin size. Our results suggest that neural activity in vivo shows a mélange of avalanches, and not temporally separated ones, and that their global activity propagation can be approximated by the principle that one spike on average triggers a little less than one spike in the next step. This implies that neural activity does not reflect a SOC state but a slightly sub-critical regime without a separation of time scales. Potential advantages of this regime may be faster information processing, and a safety margin from super-criticality, which has been linked to epilepsy. PMID:25009473

Independence of Movement Preparation and Movement Initiation.

PubMed

Haith, Adrian M; Pakpoor, Jina; Krakauer, John W

2016-03-09

Initiating a movement in response to a visual stimulus takes significantly longer than might be expected on the basis of neural transmission delays, but it is unclear why. In a visually guided reaching task, we forced human participants to move at lower-than-normal reaction times to test whether normal reaction times are strictly necessary for accurate movement. We found that participants were, in fact, capable of moving accurately ∼80 ms earlier than their reaction times would suggest. Reaction times thus include a seemingly unnecessary delay that accounts for approximately one-third of their duration. Close examination of participants' behavior in conventional reaction-time conditions revealed that they generated occasional, spontaneous errors in trials in which their reaction time was unusually short. The pattern of these errors could be well accounted for by a simple model in which the timing of movement initiation is independent of the timing of movement preparation. This independence provides an explanation for why reaction times are usually so sluggish: delaying the mean time of movement initiation relative to preparation reduces the risk that a movement will be initiated before it has been appropriately prepared. Our results suggest that preparation and initiation of movement are mechanistically independent and may have a distinct neural basis. The results also demonstrate that, even in strongly stimulus-driven tasks, presentation of a stimulus does not directly trigger a movement. Rather, the stimulus appears to trigger an internal decision whether to make a movement, reflecting a volitional rather than reactive mode of control. Copyright © 2016 the authors 0270-6474/16/363007-10$15.00/0.

Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

PubMed Central

Gan, Gabriela; Sterzer, Philipp; Marxen, Michael; Zimmermann, Ulrich S; Smolka, Michael N

2015-01-01

Although alcohol consumption is linked to increased aggression, its neural correlates have not directly been studied in humans so far. Based on a comprehensive neurobiological model of alcohol-induced aggression, we hypothesized that alcohol-induced aggression would go along with increased amygdala and ventral striatum reactivity and impaired functioning of the prefrontal cortex (PFC) under alcohol. We measured neural and behavioral correlates of alcohol-induced aggression in a provoking vs non-provoking condition with a variant of the Taylor aggression paradigm (TAP) allowing to differentiate between reactive (provoked) and proactive (unprovoked) aggression. In a placebo-controlled cross-over design with moderate alcohol intoxication (~0.6 g/kg), 35 young healthy adults performed the TAP during functional magnetic resonance imaging (fMRI). Analyses revealed that provoking vs non-provoking conditions and alcohol vs placebo increased aggression and decreased brain responses in the anterior cingulate cortex/dorso-medial PFC (provoking

Enhanced expression of FNDC5 in human embryonic stem cell-derived neural cells along with relevant embryonic neural tissues.

PubMed

Ghahrizjani, Fatemeh Ahmadi; Ghaedi, Kamran; Salamian, Ahmad; Tanhaei, Somayeh; Nejati, Alireza Shoaraye; Salehi, Hossein; Nabiuni, Mohammad; Baharvand, Hossein; Nasr-Esfahani, Mohammad Hossein

2015-02-25

Availability of human embryonic stem cells (hESCs) has enhanced the capability of basic and clinical research in the context of human neural differentiation. Derivation of neural progenitor (NP) cells from hESCs facilitates the process of human embryonic development through the generation of neuronal subtypes. We have recently indicated that fibronectin type III domain containing 5 protein (FNDC5) expression is required for appropriate neural differentiation of mouse embryonic stem cells (mESCs). Bioinformatics analyses have shown the presence of three isoforms for human FNDC5 mRNA. To differentiate which isoform of FNDC5 is involved in the process of human neural differentiation, we have used hESCs as an in vitro model for neural differentiation by retinoic acid (RA) induction. The hESC line, Royan H5, was differentiated into a neural lineage in defined adherent culture treated by RA and basic fibroblast growth factor (bFGF). We collected all cell types that included hESCs, rosette structures, and neural cells in an attempt to assess the expression of FNDC5 isoforms. There was a contiguous increase in all three FNDC5 isoforms during the neural differentiation process. Furthermore, the highest level of expression of the isoforms was significantly observed in neural cells compared to hESCs and the rosette structures known as neural precursor cells (NPCs). High expression levels of FNDC5 in human fetal brain and spinal cord tissues have suggested the involvement of this gene in neural tube development. Additional research is necessary to determine the major function of FDNC5 in this process. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study.

PubMed

McBride, Dharma; Barrett, Sean P; Kelly, Jared T; Aw, Andrew; Dagher, Alain

2006-12-01

Cues associated with drug taking can trigger relapse, drug seeking, and craving in addicted individuals. Behavioral studies suggest that drug availability and withdrawal can affect the individual response to drug cues. Moreover, the importance of subjective craving in cue-induced relapse has been questioned and an alternative model put forward according to which drug cues trigger habitual drug-seeking behaviors independently of craving. We used functional magnetic resonance imaging to compare the brain response to smoking and control videotapes in 20 healthy smokers, while varying their expectancy to smoke and abstinence levels. The neural response to cigarette cues was strongly modulated by expectancy and, to a lesser extent, abstinence. In people expecting to smoke immediately after the scan, smoking cues activated brain areas implicated in arousal, attention, and cognitive control. However, when subjects knew they would not be allowed to smoke for 4 h, there was almost no brain activation in response to smoking cues, despite equivalent reported levels of craving. In the dorsolateral prefrontal cortex, the neural response was a function of both craving and expectancy. Thalamo-cingulate connectivity, thought to be an index of arousal, was greater during expectancy than nonexpectancy. Our findings confirm the importance of expectancy in the neural response to drug cues, and lend support to the theory that these cues act on brain areas involved in arousal and attention.

Precursor processes of human self-initiated action.

PubMed

Khalighinejad, Nima; Schurger, Aaron; Desantis, Andrea; Zmigrod, Leor; Haggard, Patrick

2018-01-15

A gradual buildup of electrical potential over motor areas precedes self-initiated movements. Recently, such "readiness potentials" (RPs) were attributed to stochastic fluctuations in neural activity. We developed a new experimental paradigm that operationalized self-initiated actions as endogenous 'skip' responses while waiting for target stimuli in a perceptual decision task. We compared these to a block of trials where participants could not choose when to skip, but were instead instructed to skip. Frequency and timing of motor action were therefore balanced across blocks, so that conditions differed only in how the timing of skip decisions was generated. We reasoned that across-trial variability of EEG could carry as much information about the source of skip decisions as the mean RP. EEG variability decreased more markedly prior to self-initiated compared to externally-triggered skip actions. This convergence suggests a consistent preparatory process prior to self-initiated action. A leaky stochastic accumulator model could reproduce this convergence given the additional assumption of a systematic decrease in input noise prior to self-initiated actions. Our results may provide a novel neurophysiological perspective on the topical debate regarding whether self-initiated actions arise from a deterministic neurocognitive process, or from neural stochasticity. We suggest that the key precursor of self-initiated action may manifest as a reduction in neural noise. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Production and characterization of immortal human neural stem cell line with multipotent differentiation property.

PubMed

Kim, Seung U; Nagai, Atsushi; Nakagawa, Eiji; Choi, Hyun B; Bang, Jung H; Lee, Hong J; Lee, Myung A; Lee, Yong B; Park, In H

2008-01-01

We document the protocols and methods for the production of immortalized cell lines of human neural stem cells from the human fetal central nervous system (CNS) cells by using a retroviral vector encoding v-myc oncogene. One of the human neural stem cell lines (HB1.F3) was found to express nestin and other specific markers for human neural stem cells, giving rise to three fundamental cell types of the CNS: neurons, astrocytes, and oligodendrocytes. After transplantation into the brain of mouse model of stroke, implanted human neural stem cells were observed to migrate extensively from the site of implantation into other anatomical sites and to differentiate into neurons and glial cells.

Aberrant differentiation of the axially condensed tail bud mesenchyme in human embryos with lumbosacral myeloschisis.

PubMed

Saitsu, Hirotomo; Yamada, Shigehito; Uwabe, Chigako; Ishibashi, Makoto; Shiota, Kohei

2007-03-01

Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Recently, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the axially condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord in the junctional region of the primary and secondary neural tubes. The AM appeared to be incorporated into the most ventral part of the primary neural tube, and no cavity was observed in the AM. In this study, we report three cases of human embryos with myeloschisis in which the open primary neural tube and the closed secondary neural tube overlap dorsoventrally. In all three cases, part of the closed neural tube was located ventrally to the open neural tube in the lumbosacral region. The open and closed neural tubes appeared to be part of the primary and the AM-derived secondary neural tubes, respectively. Thus, these findings suggest that, in those embryos with myeloschisis, the AM may not be incorporated into the ventral part of the primary neural tube but aberrantly differentiate into the secondary neural tube containing cavities, leading to dorsoventral overlapping of the primary and secondary neural tubes. The aberrant differentiation of the AM in embryos with lumbosacral myeloschisis suggests that the AM plays some roles in normal as well as abnormal development of the human posterior neural tube.

Dynamic range in the C. elegans brain network

NASA Astrophysics Data System (ADS)

Antonopoulos, Chris G.

2016-01-01

We study external electrical perturbations and their responses in the brain dynamic network of the Caenorhabditis elegans soil worm, given by the connectome of its large somatic nervous system. Our analysis is inspired by a realistic experiment where one stimulates externally specific parts of the brain and studies the persistent neural activity triggered in other cortical regions. In this work, we perturb groups of neurons that form communities, identified by the walktrap community detection method, by trains of stereotypical electrical Poissonian impulses and study the propagation of neural activity to other communities by measuring the corresponding dynamic ranges and Steven law exponents. We show that when one perturbs specific communities, keeping the rest unperturbed, the external stimulations are able to propagate to some of them but not to all. There are also perturbations that do not trigger any response. We found that this depends on the initially perturbed community. Finally, we relate our findings for the former cases with low neural synchronization, self-criticality, and large information flow capacity, and interpret them as the ability of the brain network to respond to external perturbations when it works at criticality and its information flow capacity becomes maximal.

Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing

PubMed Central

Olivares, Ela I.; Lage-Castellanos, Agustín; Bobes, María A.; Iglesias, Jaime

2018-01-01

We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs) in both intra-domain (face-feature) and cross-domain (face-occupation) matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called “Fusiform Face Area”, “FFA” and “Occipital Face Area”, “OFA”, respectively), the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands. PMID:29628877

Toward developmental models of psychiatric disorders in zebrafish

PubMed Central

Norton, William H. J.

2013-01-01

Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling, and mood. Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models, and investigation of the non-biological basis of these diseases, such as environmental effects. Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation, and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds. PMID:23637652

Cortical Plasticity Induced by Spike-Triggered Microstimulation in Primate Somatosensory Cortex

PubMed Central

Song, Weiguo; Kerr, Cliff C.; Lytton, William W.; Francis, Joseph T.

2013-01-01

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. PMID:23472086

A Novel Animal Model for Investigating the Neural Basis of Focal Dystonia

DTIC Science & Technology

2017-09-01

as the predisposing condition and dry eye as an environmental trigger to model blepharospasm in rodents. This reporting year we demonstrated that 7...benign essential blepharospasm, dry eye , motor plasticity, basal ganglia, deep brain stimulation, eyelids, blinking 16. SECURITY CLASSIFICATION OF: 17...basal ganglia create the predisposing condition and that  eye   irritation from  dry   eye   is the envi‐ ronmental trigger.  Our demonstration that

Cryopreservation, Culture, and Transplantation of Human Fetal Mesencephalic Tissue into Monkeys

NASA Astrophysics Data System (ADS)

Redmond, D. E.; Naftolin, F.; Collier, T. J.; Leranth, C.; Robbins, R. J.; Sladek, C. D.; Roth, R. H.; Sladek, J. R.

1988-11-01

Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

Music and mirror neurons: from motion to 'e'motion.

PubMed

Molnar-Szakacs, Istvan; Overy, Katie

2006-12-01

The ability to create and enjoy music is a universal human trait and plays an important role in the daily life of most cultures. Music has a unique ability to trigger memories, awaken emotions and to intensify our social experiences. We do not need to be trained in music performance or appreciation to be able to reap its benefits-already as infants, we relate to it spontaneously and effortlessly. There has been a recent surge in neuroimaging investigations of the neural basis of musical experience, but the way in which the abstract shapes and patterns of musical sound can have such profound meaning to us remains elusive. Here we review recent neuroimaging evidence and suggest that music, like language, involves an intimate coupling between the perception and production of hierarchically organized sequential information, the structure of which has the ability to communicate meaning and emotion. We propose that these aspects of musical experience may be mediated by the human mirror neuron system.

Music and mirror neurons: from motion to ’e’motion

PubMed Central

Overy, Katie

2006-01-01

The ability to create and enjoy music is a universal human trait and plays an important role in the daily life of most cultures. Music has a unique ability to trigger memories, awaken emotions and to intensify our social experiences. We do not need to be trained in music performance or appreciation to be able to reap its benefits—already as infants, we relate to it spontaneously and effortlessly. There has been a recent surge in neuroimaging investigations of the neural basis of musical experience, but the way in which the abstract shapes and patterns of musical sound can have such profound meaning to us remains elusive. Here we review recent neuroimaging evidence and suggest that music, like language, involves an intimate coupling between the perception and production of hierarchically organized sequential information, the structure of which has the ability to communicate meaning and emotion. We propose that these aspects of musical experience may be mediated by the human mirror neuron system. PMID:18985111

Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells

PubMed Central

Lukiw, Walter J.; Pogue, Aileen I.

2007-01-01

Iron- and aluminum-sulfate together, at nanomolar concentrations, trigger the production of reactive oxygen species (ROS) in cultures of human brain cells. Previous studies have shown that following ROS induction, a family of pathogenic brain genes that promote inflammatory signalling, cellular apoptosis and brain cell death is significantly over-expressed. Notably, iron- and aluminum-sulfate induce genes in cultured human brain cells that exhibit expression patterns similar to those observed to be up-regulated in moderate- to late-stage Alzheimer's disease (AD). In this study we have extended our investigations to analyze the expression of micro RNA (miRNA) populations in iron- and aluminum-sulfate treated human neural cells in primary culture. The main finding was that these ROS-generating neurotoxic metal sulfates also up-regulate a specific set of miRNAs that includes miR-9, miR-125b and miR-128. Notably, these same miRNAs are up-regulated in AD brain. These findings further support the idea that iron- and aluminum-sulfates induce genotoxicity via a ROS-mediated up-regulation of specific regulatory elements and pathogenic genes that redirect brain cell fate towards progressive dysfunction and apoptotic cell death. PMID:17629564

Neuroplasticity and amblyopia: vision at the balance point.

PubMed

Tailor, Vijay K; Schwarzkopf, D Samuel; Dahlmann-Noor, Annegret H

2017-02-01

New insights into triggers and brakes of plasticity in the visual system are being translated into new treatment approaches which may improve outcomes not only in children, but also in adults. Visual experience-driven plasticity is greatest in early childhood, triggered by maturation of inhibitory interneurons which facilitate strengthening of synchronous synaptic connections, and inactivation of others. Normal binocular development leads to progressive refinement of monocular visual acuity, stereoacuity and fusion of images from both eyes. At the end of the 'critical period', structural and functional brakes such as dampening of acetylcholine receptor signalling and formation of perineuronal nets limit further synaptic remodelling. Imbalanced visual input from the two eyes can lead to imbalanced neural processing and permanent visual deficits, the commonest of which is amblyopia. The efficacy of new behavioural, physical and pharmacological interventions aiming to balance visual input and visual processing have been described in humans, and some are currently under evaluation in randomised controlled trials. Outcomes may change amblyopia treatment for children and adults, but the safety of new approaches will need careful monitoring, as permanent adverse events may occur when plasticity is re-induced after the end of the critical period.Video abstracthttp://links.lww.com/CONR/A42.

AKT-ions with a TWIST between EMT and MET.

PubMed

Tang, Huifang; Massi, Daniela; Hemmings, Brian A; Mandalà, Mario; Hu, Zhengqiang; Wicki, Andreas; Xue, Gongda

2016-09-20

The transcription factor Twist is an important regulator of cranial suture during embryogenesis. Closure of the neural tube is achieved via Twist-triggered cellular transition from an epithelial to mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT), characterized by a remarkable increase in cell motility. In the absence of Twist activity, EMT and associated phenotypic changes in cell morphology and motility can also be induced, albeit moderately, by other transcription factor families, including Snail and Zeb. Aberrant EMT triggered by Twist in human mammary tumour cells was first reported to drive metastasis to the lung in a metastatic breast cancer model. Subsequent analysis of many types of carcinoma demonstrated overexpression of these unique EMT transcription factors, which statistically correlated with worse outcome, indicating their potential as biomarkers in the clinic. However, the mechanisms underlying their activation remain unclear. Interestingly, increasing evidence indicates they are selectively activated by distinct intracellular kinases, thereby acting as downstream effectors facilitating transduction of cytoplasmic signals into nucleus and reprogramming EMT and mesenchymal-epithelial transition (MET) transcription to control cell plasticity. Understanding these relationships and emerging data indicating differential phosphorylation of Twist leads to complex and even paradoxical functionalities, will be vital to unlocking their potential in clinical settings.

Using LSTM recurrent neural networks for monitoring the LHC superconducting magnets

NASA Astrophysics Data System (ADS)

Wielgosz, Maciej; Skoczeń, Andrzej; Mertik, Matej

2017-09-01

The superconducting LHC magnets are coupled with an electronic monitoring system which records and analyzes voltage time series reflecting their performance. A currently used system is based on a range of preprogrammed triggers which launches protection procedures when a misbehavior of the magnets is detected. All the procedures used in the protection equipment were designed and implemented according to known working scenarios of the system and are updated and monitored by human operators. This paper proposes a novel approach to monitoring and fault protection of the Large Hadron Collider (LHC) superconducting magnets which employs state-of-the-art Deep Learning algorithms. Consequently, the authors of the paper decided to examine the performance of LSTM recurrent neural networks for modeling of voltage time series of the magnets. In order to address this challenging task different network architectures and hyper-parameters were used to achieve the best possible performance of the solution. The regression results were measured in terms of RMSE for different number of future steps and history length taken into account for the prediction. The best result of RMSE = 0 . 00104 was obtained for a network of 128 LSTM cells within the internal layer and 16 steps history buffer.

Near-infrared signals associated with electrical stimulation of peripheral nerves

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

2009-02-01

We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

The neural basis of functional neuroimaging signal with positron and single-photon emission tomography.

PubMed

Sestini, S

2007-07-01

Functional imaging techniques such as positron and single-photon emission tomography exploit the relationship between neural activity, energy demand and cerebral blood flow to functionally map the brain. Despite the fact that neurobiological processes are not completely understood, several results have revealed the signals that trigger the metabolic and vascular changes accompanying variations in neural activity. Advances in this field have demonstrated that release of the major excitatory neurotransmitter glutamate initiates diverse signaling processes between neurons, astrocytes and blood perfusion, and that this signaling is crucial for the occurrence of brain imaging signals. Better understanding of the neural sites of energy consumption and the temporal correlation between energy demand, energy consumption and associated cerebrovascular hemodynamics gives novel insight into the potential of these imaging tools in the study of metabolic neurodegenerative disorders.

Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

PubMed

Jain, Sonia P; Gulhane, Sachin; Pandey, Neha; Bisne, Esha

2015-01-01

Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management.

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

PubMed

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

2015-01-01

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

Cyclin-dependent kinase 4 signaling acts as a molecular switch between syngenic differentiation and neural transdifferentiation in human mesenchymal stem cells

PubMed Central

Lee, Janet; Baek, Jeong-Hwa; Choi, Kyu-Sil; Kim, Hyun-Soo; Park, Hye-Young; Ha, Geun-Hyoung; Park, Ho; Lee, Kyo-Won; Lee, Chang Geun; Yang, Dong-Yun; Moon, Hyo Eun; Paek, Sun Ha; Lee, Chang-Woo

2013-01-01

Multipotent mesenchymal stem/stromal cells (MSCs) are capable of differentiating into a variety of cell types from different germ layers. However, the molecular and biochemical mechanisms underlying the transdifferentiation of MSCs into specific cell types still need to be elucidated. In this study, we unexpectedly found that treatment of human adipose- and bone marrow-derived MSCs with cyclin-dependent kinase (CDK) inhibitor, in particular CDK4 inhibitor, selectively led to transdifferentiation into neural cells with a high frequency. Specifically, targeted inhibition of CDK4 expression using recombinant adenovial shRNA induced the neural transdifferentiation of human MSCs. However, the inhibition of CDK4 activity attenuated the syngenic differentiation of human adipose-derived MSCs. Importantly, the forced regulation of CDK4 activity showed reciprocal reversibility between neural differentiation and dedifferentiation of human MSCs. Together, these results provide novel molecular evidence underlying the neural transdifferentiation of human MSCs; in addition, CDK4 signaling appears to act as a molecular switch from syngenic differentiation to neural transdifferentiation of human MSCs. PMID:23324348

Vulnerability of the neural circuitry underlying sexual behavior to chronic adult exposure to oral bisphenol a in male mice.

PubMed

Picot, Marie; Naulé, Lydie; Marie-Luce, Clarisse; Martini, Mariangela; Raskin, Kalina; Grange-Messent, Valérie; Franceschini, Isabelle; Keller, Matthieu; Mhaouty-Kodja, Sakina

2014-02-01

There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.

Neural Mechanisms of Cognitive Dissonance (Revised): An EEG Study.

PubMed

Colosio, Marco; Shestakova, Anna; Nikulin, Vadim V; Blagovechtchenski, Evgeny; Klucharev, Vasily

2017-05-17

Cognitive dissonance theory suggests that our preferences are modulated by the mere act of choosing. A choice between two similarly valued alternatives creates psychological tension (cognitive dissonance) that is reduced by a postdecisional reevaluation of the alternatives. We measured EEG of human subjects during rest and free-choice paradigm. Our study demonstrates that choices associated with stronger cognitive dissonance trigger a larger negative frontocentral evoked response similar to error-related negativity, which has in turn been implicated in general performance monitoring. Furthermore, the amplitude of the evoked response is correlated with the reevaluation of the alternatives. We also found a link between individual neural dynamics (long-range temporal correlations) of the frontocentral cortices during rest and follow-up neural and behavioral effects of cognitive dissonance. Individuals with stronger resting-state long-range temporal correlations demonstrated a greater postdecisional reevaluation of the alternatives and larger evoked brain responses associated with stronger cognitive dissonance. Thus, our results suggest that cognitive dissonance is reflected in both resting-state and choice-related activity of the prefrontal cortex as part of the general performance-monitoring circuitry. SIGNIFICANCE STATEMENT Contrary to traditional decision theory, behavioral studies repeatedly demonstrate that our preferences are modulated by the mere act of choosing. Difficult choices generate psychological (cognitive) dissonance, which is reduced by the postdecisional devaluation of unchosen options. We found that decisions associated with a higher level of cognitive dissonance elicited a stronger negative frontocentral deflection that peaked ∼60 ms after the response. This activity shares similar spatial and temporal features as error-related negativity, the electrophysiological correlate of performance monitoring. Furthermore, the frontocentral resting-state activity predicted the individual magnitude of preference change and the strength of cognitive dissonance-related neural activity. Copyright © 2017 Colosio et al.

Neural Mechanisms of Cognitive Dissonance (Revised): An EEG Study

PubMed Central

Nikulin, Vadim V.; Blagovechtchenski, Evgeny

2017-01-01

Cognitive dissonance theory suggests that our preferences are modulated by the mere act of choosing. A choice between two similarly valued alternatives creates psychological tension (cognitive dissonance) that is reduced by a postdecisional reevaluation of the alternatives. We measured EEG of human subjects during rest and free-choice paradigm. Our study demonstrates that choices associated with stronger cognitive dissonance trigger a larger negative frontocentral evoked response similar to error-related negativity, which has in turn been implicated in general performance monitoring. Furthermore, the amplitude of the evoked response is correlated with the reevaluation of the alternatives. We also found a link between individual neural dynamics (long-range temporal correlations) of the frontocentral cortices during rest and follow-up neural and behavioral effects of cognitive dissonance. Individuals with stronger resting-state long-range temporal correlations demonstrated a greater postdecisional reevaluation of the alternatives and larger evoked brain responses associated with stronger cognitive dissonance. Thus, our results suggest that cognitive dissonance is reflected in both resting-state and choice-related activity of the prefrontal cortex as part of the general performance-monitoring circuitry. SIGNIFICANCE STATEMENT Contrary to traditional decision theory, behavioral studies repeatedly demonstrate that our preferences are modulated by the mere act of choosing. Difficult choices generate psychological (cognitive) dissonance, which is reduced by the postdecisional devaluation of unchosen options. We found that decisions associated with a higher level of cognitive dissonance elicited a stronger negative frontocentral deflection that peaked ∼60 ms after the response. This activity shares similar spatial and temporal features as error-related negativity, the electrophysiological correlate of performance monitoring. Furthermore, the frontocentral resting-state activity predicted the individual magnitude of preference change and the strength of cognitive dissonance-related neural activity. PMID:28438968

Neurophysiology Summary

NASA Technical Reports Server (NTRS)

Paloski, William H.

2001-01-01

The terrestrial gravitational field serves as an important orientation reference for human perception and movement, being continually monitored by sensory receptors in the skin, muscles, joints, and vestibular otolith organs. Cues from these graviceptors are used by the brain to estimate spatial orientation and to control balance and movement. Changes in these cues associated with the tonic changes in gravity (gravito-inertial force),during the launch and entry phases of space flight missions result in altered perceptions, degraded motor control performance, and in some cases, "motion" sickness during, and for a period of time after, the g-transitions. In response to these transitions, however, physiological and behavioral response mechanisms are triggered to compensate for altered graviceptor cues and/or to adapt to the new sensory environment. Basic research in the neurophysiology discipline is focused on understanding the characteristic features of and the underlying mechanisms for the normal human response to tonic changes in the gravito-inertial force environment. These studies address fundamental questions regarding the role of graviceptors in orientation and movement in the terrestrial environment, as well as the capacity, specificity, and modes for neural plasticity in the sensory-motor and perceptual systems of the brain. At the 2001 workshop basic research studies were presented addressing: neuroanatomical responses to altered gravity environments, the neural mechanisms for resolving the ambiguity between tilting and translational stimuli in otolith organ sensory input, interactions between the vestibular system and the autonomic nervous system , the roles of haptic and visual cues in spatial orientation, mechanisms for training environment-appropriate sensorimotor responses triggered by environment-specific context cues, and studies of sensori-motor control of posture and locomotion in the terrestrial environment with and without recent exposure to space flight. Building on these basic research studies are more applied studies focused on the development of countermeasures to the untoward neurophysiological responses to space flight. At the 2001 workshop, applied research studies were presented addressing issues related to the use of rotational artificial gravity (centripetal acceleration) as a multisystem (bone, muscle, cardiovascular, and, perhaps, neurovestibular) countermeasure. Also presented was a clinical study reporting on a new rating system for clinical evaluation of postflight functional neurological status.

WDR62 Regulates Early Neural and Glial Progenitor Specification of Human Pluripotent Stem Cells

PubMed Central

Alshawaf, Abdullah J.; Antonic, Ana; Skafidas, Efstratios

2017-01-01

Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively. These findings may signify a role of WDR62 in specifying intermediate neural and glial progenitors during human pluripotent stem cell differentiation. PMID:28690640

Model-Based Adaptive Event-Triggered Control of Strict-Feedback Nonlinear Systems.

PubMed

Li, Yuan-Xin; Yang, Guang-Hong

2018-04-01

This paper is concerned with the adaptive event-triggered control problem of nonlinear continuous-time systems in strict-feedback form. By using the event-sampled neural network (NN) to approximate the unknown nonlinear function, an adaptive model and an associated event-triggered controller are designed by exploiting the backstepping method. In the proposed method, the feedback signals and the NN weights are aperiodically updated only when the event-triggered condition is violated. A positive lower bound on the minimum intersample time is guaranteed to avoid accumulation point. The closed-loop stability of the resulting nonlinear impulsive dynamical system is rigorously proved via Lyapunov analysis under an adaptive event sampling condition. In comparing with the traditional adaptive backstepping design with a fixed sample period, the event-triggered method samples the state and updates the NN weights only when it is necessary. Therefore, the number of transmissions can be significantly reduced. Finally, two simulation examples are presented to show the effectiveness of the proposed control method.

Salient, Irrelevant Sounds Reflexively Induce Alpha Rhythm Desynchronization in Parallel with Slow Potential Shifts in Visual Cortex.

PubMed

Störmer, Viola; Feng, Wenfeng; Martinez, Antigona; McDonald, John; Hillyard, Steven

2016-03-01

Recent findings suggest that a salient, irrelevant sound attracts attention to its location involuntarily and facilitates processing of a colocalized visual event [McDonald, J. J., Störmer, V. S., Martinez, A., Feng, W. F., & Hillyard, S. A. Salient sounds activate human visual cortex automatically. Journal of Neuroscience, 33, 9194-9201, 2013]. Associated with this cross-modal facilitation is a sound-evoked slow potential over the contralateral visual cortex termed the auditory-evoked contralateral occipital positivity (ACOP). Here, we further tested the hypothesis that a salient sound captures visual attention involuntarily by examining sound-evoked modulations of the occipital alpha rhythm, which has been strongly associated with visual attention. In two purely auditory experiments, lateralized irrelevant sounds triggered a bilateral desynchronization of occipital alpha-band activity (10-14 Hz) that was more pronounced in the hemisphere contralateral to the sound's location. The timing of the contralateral alpha-band desynchronization overlapped with that of the ACOP (∼240-400 msec), and both measures of neural activity were estimated to arise from neural generators in the ventral-occipital cortex. The magnitude of the lateralized alpha desynchronization was correlated with ACOP amplitude on a trial-by-trial basis and between participants, suggesting that they arise from or are dependent on a common neural mechanism. These results support the hypothesis that the sound-induced alpha desynchronization and ACOP both reflect the involuntary cross-modal orienting of spatial attention to the sound's location.

Artificial Neural Network as the FPGA Trigger in the Cyclone V based Front-End for a Detection of Neutrino-Origin Showers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szadkowski, Zbigniew; Glas, Dariusz; Pytel, Krzysztof

Neutrinos play a fundamental role in the understanding of the origin of ultra-high-energy cosmic rays. They interact through charged and neutral currents in the atmosphere generating extensive air showers. However, their a very low rate of events potentially generated by neutrinos is a significant challenge for a detection technique and requires both sophisticated algorithms and high-resolution hardware. A trigger based on a artificial neural network was implemented into the Cyclone{sup R} V E FPGA 5CEFA9F31I7 - the heart of the prototype Front-End boards developed for tests of new algorithms in the Pierre Auger surface detectors. Showers for muon and taumore » neutrino initiating particles on various altitudes, angles and energies were simulated in CORSICA and Offline platforms giving pattern of ADC traces in Auger water Cherenkov detectors. The 3-layer 12-8-1 neural network was taught in MATLAB by simulated ADC traces according the Levenberg-Marquardt algorithm. Results show that a probability of a ADC traces generation is very low due to a small neutrino cross-section. Nevertheless, ADC traces, if occur, for 1-10 EeV showers are relatively short and can be analyzed by 16-point input algorithm. We optimized the coefficients from MATLAB to get a maximal range of potentially registered events and for fixed-point FPGA processing to minimize calculation errors. New sophisticated triggers implemented in Cyclone{sup R} V E FPGAs with large amount of DSP blocks, embedded memory running with 120 - 160 MHz sampling may support a discovery of neutrino events in the Pierre Auger Observatory. (authors)« less

Neural Conflict–Control Mechanisms Improve Memory for Target Stimuli

PubMed Central

Krebs, Ruth M.; Boehler, Carsten N.; De Belder, Maya; Egner, Tobias

2015-01-01

According to conflict-monitoring models, conflict serves as an internal signal for reinforcing top-down attention to task-relevant information. While evidence based on measures of ongoing task performance supports this idea, implications for long-term consequences, that is, memory, have not been tested yet. Here, we evaluated the prediction that conflict-triggered attentional enhancement of target-stimulus processing should be associated with superior subsequent memory for those stimuli. By combining functional magnetic resonance imaging (fMRI) with a novel variant of a face-word Stroop task that employed trial-unique face stimuli as targets, we were able to assess subsequent (incidental) memory for target faces as a function of whether a given face had previously been accompanied by congruent, neutral, or incongruent (conflicting) distracters. In line with our predictions, incongruent distracters not only induced behavioral conflict, but also gave rise to enhanced memory for target faces. Moreover, conflict-triggered neural activity in prefrontal and parietal regions was predictive of subsequent retrieval success, and displayed conflict-enhanced functional coupling with medial-temporal lobe regions. These data provide support for the proposal that conflict evokes enhanced top-down attention to task-relevant stimuli, thereby promoting their encoding into long-term memory. Our findings thus delineate the neural mechanisms of a novel link between cognitive control and memory. PMID:24108799

Deconstruction of spatial integrity in visual stimulus detected by modulation of synchronized activity in cat visual cortex.

PubMed

Zhou, Zhiyi; Bernard, Melanie R; Bonds, A B

2008-04-02

Spatiotemporal relationships among contour segments can influence synchronization of neural responses in the primary visual cortex. We performed a systematic study to dissociate the impact of spatial and temporal factors in the signaling of contour integration via synchrony. In addition, we characterized the temporal evolution of this process to clarify potential underlying mechanisms. With a 10 x 10 microelectrode array, we recorded the simultaneous activity of multiple cells in the cat primary visual cortex while stimulating with drifting sine-wave gratings. We preserved temporal integrity and systematically degraded spatial integrity of the sine-wave gratings by adding spatial noise. Neural synchronization was analyzed in the time and frequency domains by conducting cross-correlation and coherence analyses. The general association between neural spike trains depends strongly on spatial integrity, with coherence in the gamma band (35-70 Hz) showing greater sensitivity to the change of spatial structure than other frequency bands. Analysis of the temporal dynamics of synchronization in both time and frequency domains suggests that spike timing synchronization is triggered nearly instantaneously by coherent structure in the stimuli, whereas frequency-specific oscillatory components develop more slowly, presumably through network interactions. Our results suggest that, whereas temporal integrity is required for the generation of synchrony, spatial integrity is critical in triggering subsequent gamma band synchronization.

Machine Learning and Quantum Mechanics

NASA Astrophysics Data System (ADS)

Chapline, George

The author has previously pointed out some similarities between selforganizing neural networks and quantum mechanics. These types of neural networks were originally conceived of as away of emulating the cognitive capabilities of the human brain. Recently extensions of these networks, collectively referred to as deep learning networks, have strengthened the connection between self-organizing neural networks and human cognitive capabilities. In this note we consider whether hardware quantum devices might be useful for emulating neural networks with human-like cognitive capabilities, or alternatively whether implementations of deep learning neural networks using conventional computers might lead to better algorithms for solving the many body Schrodinger equation.

High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress.

PubMed

Chen, Xi; Shen, Wei-Bin; Yang, Penghua; Dong, Daoyin; Sun, Winny; Yang, Peixin

2018-06-01

Maternal diabetes induces neural tube defects by suppressing neurogenesis in the developing neuroepithelium. Our recent study further revealed that high glucose inhibited embryonic stem cell differentiation into neural lineage cells. However, the mechanism whereby high glucose suppresses neural differentiation is unclear. To investigate whether high glucose-induced oxidative stress and endoplasmic reticulum (ER) stress lead to the inhibition of neural differentiation, the effect of high glucose on neural stem cell (the C17.2 cell line) differentiation was examined. Neural stem cells were cultured in normal glucose (5 mM) or high glucose (25 mM) differentiation medium for 3, 5, and 7 days. High glucose suppressed neural stem cell differentiation by significantly decreasing the expression of the neuron marker Tuj1 and the glial cell marker GFAP and the numbers of Tuj1 + and GFAP + cells. The antioxidant enzyme superoxide dismutase mimetic Tempol reversed high glucose-decreased Tuj1 and GFAP expression and restored the numbers of neurons and glial cells differentiated from neural stem cells. Hydrogen peroxide treatment imitated the inhibitory effect of high glucose on neural stem cell differentiation. Both high glucose and hydrogen peroxide triggered ER stress, whereas Tempol blocked high glucose-induced ER stress. The ER stress inhibitor, 4-phenylbutyrate, abolished the inhibition of high glucose or hydrogen peroxide on neural stem cell differentiation. Thus, oxidative stress and its resultant ER stress mediate the inhibitory effect of high glucose on neural stem cell differentiation.

Mechanosensitive neurons on the internal reproductive tract contribute to egg-laying-induced acetic acid attraction in Drosophila

PubMed Central

Gou, Bin; Liu, Ying; Guntur, Ananya R.; Stern, Ulrich; Yang, Chung-Hui

2014-01-01

Selecting a suitable site to deposit their eggs is an important reproductive need of Drosophila females. While their choosiness towards egg-laying sites is well documented, the specific neural mechanism that activates females’ search for attractive egg-laying sites is not known. Here we show that distention/contraction of females’ internal reproductive tract triggered by egg-delivery through the tract plays a critical role in activating such search. We found that females start to exhibit acetic acid attraction prior to depositing each egg but no attraction when they are not laying eggs. Artificially distending the reproductive tract triggers acetic acid attraction in non-egg-laying females whereas silencing the mechanosensitive neurons we identified that can sense the contractile status of the tract eliminates such attraction. Our work uncovers the circuit basis of an important reproductive need of Drosophila females and provides a simple model to dissect the neural mechanism that underlies a reproductive need-induced behavioral modification. PMID:25373900

Gap Junction Proteins in the Blood-Brain Barrier Control Nutrient-Dependent Reactivation of Drosophila Neural Stem Cells

PubMed Central

Spéder, Pauline; Brand, Andrea H.

2014-01-01

Summary Neural stem cells in the adult brain exist primarily in a quiescent state but are reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila CNS, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. Feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/insulin-like growth factor pathway in underlying neural stem cells and stimulating their growth and proliferation. Here we show that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behavior, enabling glia to respond to nutritional signals and reactivate quiescent stem cells. We propose that gap junctions in the blood-brain barrier are required to translate metabolic signals into synchronized calcium pulses and insulin secretion. PMID:25065772

Closed-loop optical neural stimulation based on a 32-channel low-noise recording system with online spike sorting

NASA Astrophysics Data System (ADS)

Nguyen, T. K. T.; Navratilova, Z.; Cabral, H.; Wang, L.; Gielen, G.; Battaglia, F. P.; Bartic, C.

2014-08-01

Objective. Closed-loop operation of neuro-electronic systems is desirable for both scientific and clinical (neuroprosthesis) applications. Integrating optical stimulation with recording capability further enhances the selectivity of neural stimulation. We have developed a system enabling the local delivery of optical stimuli and the simultaneous electrical measuring of the neural activities in a closed-loop approach. Approach. The signal analysis is performed online through the implementation of a template matching algorithm. The system performance is demonstrated with the recorded data and in awake rats. Main results. Specifically, the neural activities are simultaneously recorded, detected, classified online (through spike sorting) from 32 channels, and used to trigger a light emitting diode light source using generated TTL signals. Significance. A total processing time of 8 ms is achieved, suitable for optogenetic studies of brain mechanisms online.

Comparative Analysis of the Conformation, Aggregation, Interaction, and Fibril Morphologies of Human α-, β-, and γ-Synuclein Proteins.

PubMed

Jain, Manish Kumar; Singh, Priyanka; Roy, Sneha; Bhat, Rajiv

2018-06-13

The human synuclein (syn) family is comprised of α-, β-, and γ-syn proteins. α-syn has the highest propensity for aggregation, and its aggregated forms accumulate in Lewy bodies (LB) and Lewy neurites, which are involved in Parkinson's disease (PD). β- and γ-syn are absent in LB, and their exact role is still enigmatic. β-syn does not form aggregates under physiological conditions (pH 7.4), while γ-syn is associated with neural and non-neural diseases like breast cancer. Because of their similar regional distribution in the brain, natively unfolded structure, and high degree of sequence homology, studying the effect of the environment on their conformation, interactions, fibrillation, and fibril morphologies has become important. Our studies show that high temperatures, low pH values, and high concentrations increase the rate of fibrillation of α- and γ-syn, while β-syn forms fibrils only at low pH. Fibril morphologies are strongly dependent on the immediate environment of the proteins. The high molar ratio of β-syn inhibits the fibrillation in α- and γ-syn. However, preformed seed fibrils of β- and γ-syn do not affect fibrillation of α-syn. Surface plasmon resonance data show that interactions between α- and β-syn, β- and γ-syn, and α- and γ-syn are weak to moderate in nature and can be physiologically significant in counteracting several adverse conditions in the cells that trigger their aggregation. These studies could be helpful in understanding collective human synuclein behavior in various protein environments and in the modulation of the homeostasis between β-syn and healthy versus corrupt α- and γ-syn that can potentially affect PD pathology.

Scalable Expansion of Human Pluripotent Stem Cell-Derived Neural Progenitors in Stirred Suspension Bioreactor Under Xeno-free Condition.

PubMed

Nemati, Shiva; Abbasalizadeh, Saeed; Baharvand, Hossein

2016-01-01

Recent advances in neural differentiation technology have paved the way to generate clinical grade neural progenitor populations from human pluripotent stem cells. These cells are an excellent source for the production of neural cell-based therapeutic products to treat incurable central nervous system disorders such as Parkinson's disease and spinal cord injuries. This progress can be complemented by the development of robust bioprocessing technologies for large scale expansion of clinical grade neural progenitors under GMP conditions for promising clinical use and drug discovery applications. Here, we describe a protocol for a robust, scalable expansion of human neural progenitor cells from pluripotent stem cells as 3D aggregates in a stirred suspension bioreactor. The use of this platform has resulted in easily expansion of neural progenitor cells for several passages with a fold increase of up to 4.2 over a period of 5 days compared to a maximum 1.5-2-fold increase in the adherent static culture over a 1 week period. In the bioreactor culture, these cells maintained self-renewal, karyotype stability, and cloning efficiency capabilities. This approach can be also used for human neural progenitor cells derived from other sources such as the human fetal brain.

WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate.

PubMed

Leung, Alan W; Murdoch, Barbara; Salem, Ahmed F; Prasad, Maneeshi S; Gomez, Gustavo A; García-Castro, Martín I

2016-02-01

Neural crest (NC) cells arise early in vertebrate development, migrate extensively and contribute to a diverse array of ectodermal and mesenchymal derivatives. Previous models of NC formation suggested derivation from neuralized ectoderm, via meso-ectodermal, or neural-non-neural ectoderm interactions. Recent studies using bird and amphibian embryos suggest an earlier origin of NC, independent of neural and mesodermal tissues. Here, we set out to generate a model in which to decipher signaling and tissue interactions involved in human NC induction. Our novel human embryonic stem cell (ESC)-based model yields high proportions of multipotent NC cells (expressing SOX10, PAX7 and TFAP2A) in 5 days. We demonstrate a crucial role for WNT/β-catenin signaling in launching NC development, while blocking placodal and surface ectoderm fates. We provide evidence of the delicate temporal effects of BMP and FGF signaling, and find that NC development is separable from neural and/or mesodermal contributions. We further substantiate the notion of a neural-independent origin of NC through PAX6 expression and knockdown studies. Finally, we identify a novel pre-neural border state characterized by early WNT/β-catenin signaling targets that displays distinct responses to BMP and FGF signaling from the traditional neural border genes. In summary, our work provides a fast and efficient protocol for human NC differentiation under signaling constraints similar to those identified in vivo in model organisms, and strengthens a framework for neural crest ontogeny that is separable from neural and mesodermal fates. © 2016. Published by The Company of Biologists Ltd.

Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells.

PubMed

Li, Yuanyuan; Wang, Ran; Qiao, Nan; Peng, Guangdun; Zhang, Ke; Tang, Ke; Han, Jing-Dong J; Jing, Naihe

2017-12-01

Proper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA sequencing analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0); differentiation initiation (days 2, 4, and 6); neural commitment (days 8-10); neural progenitor cell proliferation (days 12, 14, and 16); and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-sequencing data with several other transcriptome profiling datasets from mice and humans indicated that Module 3 associated with the day 8-10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR/Cas9-mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia-related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

P3 amplitude attenuation secondary to increases in target-to-target interval (TTI) during spatial serial order recall: Implications for EEG models of working memory function.

PubMed

Hochberger, William C; Axelrod, Jenna L; Sarapas, Casey; Shankman, Stewart A; Hill, S Kristian

2018-06-08

Research suggests that increasing delays in stimulus read-out can trigger declines in serial order recall accuracy due to increases in cognitive demand imposed by the delay; however, the exact neural mechanisms associated with this decline are unclear. Changes in neural resource allocation present as the ideal target and can easily be monitored by examining changes in the amplitude of an ERP component known as the P3. Changes in P3 amplitude secondary to exogenous pacing of stimulus read-out via increased target-to-target intervals (TTI) during recall could reflect decreased neural resource allocation due to increased cognitive demand. This shift in resource allocation could result in working memory storage decay and the declines in serial order accuracy described by prior research. In order to examine this potential effect, participants were administered a spatial serial order processing task, with the recall series consisting of a series of correct ("match") or incorrect ("non-match" or "oddball") stimuli. Moreover, the recall series included either a brief (500ms) or extended (2000ms) delay between stimuli. Results were significant for the presence of a P3 response to non-match stimuli for both experimental conditions, and attenuation of P3 amplitude secondary to the increase in target-to-target interval (TTI). These findings suggest that extending the delay between target recognition could increase cognitive demand and trigger a decrease in neural resource allocation that results in a decay of working memory stores.

Extracting the Behaviorally Relevant Stimulus: Unique Neural Representation of Farnesol, a Component of the Recruitment Pheromone of Bombus terrestris

PubMed Central

Strube-Bloss, Martin F.; Brown, Austin; Spaethe, Johannes; Schmitt, Thomas; Rössler, Wolfgang

2015-01-01

To trigger innate behavior, sensory neural networks are pre-tuned to extract biologically relevant stimuli. Many male-female or insect-plant interactions depend on this phenomenon. Especially communication among individuals within social groups depends on innate behaviors. One example is the efficient recruitment of nest mates by successful bumblebee foragers. Returning foragers release a recruitment pheromone in the nest while they perform a ‘dance’ behavior to activate unemployed nest mates. A major component of this pheromone is the sesquiterpenoid farnesol. How farnesol is processed and perceived by the olfactory system, has not yet been identified. It is much likely that processing farnesol involves an innate mechanism for the extraction of relevant information to trigger a fast and reliable behavioral response. To test this hypothesis, we used population response analyses of 100 antennal lobe (AL) neurons recorded in alive bumblebee workers under repeated stimulation with four behaviorally different, but chemically related odorants (geraniol, citronellol, citronellal and farnesol). The analysis identified a unique neural representation of the recruitment pheromone component compared to the other odorants that are predominantly emitted by flowers. The farnesol induced population activity in the AL allowed a reliable separation of farnesol from all other chemically related odor stimuli we tested. We conclude that the farnesol induced population activity may reflect a predetermined representation within the AL-neural network allowing efficient and fast extraction of a behaviorally relevant stimulus. Furthermore, the results show that population response analyses of multiple single AL-units may provide a powerful tool to identify distinct representations of behaviorally relevant odors. PMID:26340263

Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement

PubMed Central

Eaton, Ryan W.; Libey, Tyler

2017-01-01

Operant conditioning of neural activity has typically been performed under controlled behavioral conditions using food reinforcement. This has limited the duration and behavioral context for neural conditioning. To reward cell activity in unconstrained primates, we sought sites in nucleus accumbens (NAc) whose stimulation reinforced operant responding. In three monkeys, NAc stimulation sustained performance of a manual target-tracking task, with response rates that increased monotonically with increasing NAc stimulation. We recorded activity of single motor cortex neurons and documented their modulation with wrist force. We conditioned increased firing rates with the monkey seated in the training booth and during free behavior in the cage using an autonomous head-fixed recording and stimulating system. Spikes occurring above baseline rates triggered single or multiple electrical pulses to the reinforcement site. Such rate-contingent, unit-triggered stimulation was made available for periods of 1–3 min separated by 3–10 min time-out periods. Feedback was presented as event-triggered clicks both in-cage and in-booth, and visual cues were provided in many in-booth sessions. In-booth conditioning produced increases in single neuron firing probability with intracranial reinforcement in 48 of 58 cells. Reinforced cell activity could rise more than five times that of non-reinforced activity. In-cage conditioning produced significant increases in 21 of 33 sessions. In-cage rate changes peaked later and lasted longer than in-booth changes, but were often comparatively smaller, between 13 and 18% above non-reinforced activity. Thus intracranial stimulation reinforced volitional increases in cortical firing rates during both free behavior and a controlled environment, although changes in the latter were more robust. NEW & NOTEWORTHY Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering activity-dependent stimuli to an intracranial reinforcement site (nucleus accumbens). We conditioned increased firing rates with the monkeys seated in a training booth and also, for the first time, during free behavior in a cage using an autonomous head-fixed BCI. PMID:28031396

Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement.

PubMed

Eaton, Ryan W; Libey, Tyler; Fetz, Eberhard E

2017-03-01

Operant conditioning of neural activity has typically been performed under controlled behavioral conditions using food reinforcement. This has limited the duration and behavioral context for neural conditioning. To reward cell activity in unconstrained primates, we sought sites in nucleus accumbens (NAc) whose stimulation reinforced operant responding. In three monkeys, NAc stimulation sustained performance of a manual target-tracking task, with response rates that increased monotonically with increasing NAc stimulation. We recorded activity of single motor cortex neurons and documented their modulation with wrist force. We conditioned increased firing rates with the monkey seated in the training booth and during free behavior in the cage using an autonomous head-fixed recording and stimulating system. Spikes occurring above baseline rates triggered single or multiple electrical pulses to the reinforcement site. Such rate-contingent, unit-triggered stimulation was made available for periods of 1-3 min separated by 3-10 min time-out periods. Feedback was presented as event-triggered clicks both in-cage and in-booth, and visual cues were provided in many in-booth sessions. In-booth conditioning produced increases in single neuron firing probability with intracranial reinforcement in 48 of 58 cells. Reinforced cell activity could rise more than five times that of non-reinforced activity. In-cage conditioning produced significant increases in 21 of 33 sessions. In-cage rate changes peaked later and lasted longer than in-booth changes, but were often comparatively smaller, between 13 and 18% above non-reinforced activity. Thus intracranial stimulation reinforced volitional increases in cortical firing rates during both free behavior and a controlled environment, although changes in the latter were more robust. NEW & NOTEWORTHY Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering activity-dependent stimuli to an intracranial reinforcement site (nucleus accumbens). We conditioned increased firing rates with the monkeys seated in a training booth and also, for the first time, during free behavior in a cage using an autonomous head-fixed BCI. Copyright © 2017 the American Physiological Society.

[Insulin resistance as a mechanism of adaptation during human evolution].

PubMed

Ricart, W; Fernández-Real, J M

2010-10-01

The recent application of concepts of evolution to human disease is proving useful to understand certain pathophysiological mechanisms of different entities that span genomic alterations of immunity, respiratory and hormone function, and the circulatory and neural systems. However, effort has concentrated on explaining the keys to adaptation that define human metabolism and, since the early 1960s, several theories have been developed. This article reviews some of the hypotheses postulated in recent years on the potential benefit of insulin resistance and discusses the most recent knowledge. The concept of the thrifty gene seems to have been definitively refuted by current knowledge. The current paradigm describes an interaction between the metabolic and the immune systems resulting from their coevolution, promoted by evolutionary pressures triggered by fasting, infection and intake of different foods. The activation and regulation of these ancient mechanisms in integrated and interdependent areas defines insulin resistance as a survival strategy that is critical during fasting and in the fight against infection. The relationship with some components of the diet and, particularly, with the symbiotic intestinal microflora points to new paradigms in understanding the pathophysiology of obesity, metabolic syndrome and type 2 diabetes mellitus. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

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

PubMed

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.

Multipotent Caudal Neural Progenitors Derived from Human Pluripotent Stem Cells That Give Rise to Lineages of the Central and Peripheral Nervous System

PubMed Central

Hasegawa, Kouichi; Menheniott, Trevelyan; Rollo, Ben; Zhang, Dongcheng; Hough, Shelley; Alshawaf, Abdullah; Febbraro, Fabia; Ighaniyan, Samiramis; Leung, Jessie; Elliott, David A.; Newgreen, Donald F.; Pera, Martin F.

2015-01-01

Abstract The caudal neural plate is a distinct region of the embryo that gives rise to major progenitor lineages of the developing central and peripheral nervous system, including neural crest and floor plate cells. We show that dual inhibition of the glycogen synthase kinase 3β and activin/nodal pathways by small molecules differentiate human pluripotent stem cells (hPSCs) directly into a preneuroepithelial progenitor population we named “caudal neural progenitors” (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high similarities to embryonic caudal neural plate cells in their lineage differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2 signaling efficiently directs their fate to neural crest/roof plate cells, floor plate cells, and caudally specified neuroepithelial cells, respectively. Neural crest derived from CNPs differentiated to neural crest derivatives and demonstrated extensive migratory properties in vivo. Importantly, we also determined the key extrinsic factors specifying CNPs from human embryonic stem cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify a multipotent neural progenitor derived from hPSCs, that is the precursor for major neural lineages of the embryonic caudal neural tube. Stem Cells 2015;33:1759–1770 PMID:25753817

The Social Misperception Syndrome in Children with Learning Disabilities: Social Causes versus Neurological Variables.

ERIC Educational Resources Information Center

Spafford, Carol Sullivan; Grosser, George S.

1993-01-01

This article synthesizes the research defining social problems of some children with learning disabilities, especially the role of communication skills deficits. Traditional emphases on family dysfunction, school failure, or personality disturbances are seen to be negated by research which suggests that neural aberrations trigger deficient…

Optimization of neural network architecture using genetic programming improves detection and modeling of gene-gene interactions in studies of human diseases

PubMed Central

Ritchie, Marylyn D; White, Bill C; Parker, Joel S; Hahn, Lance W; Moore, Jason H

2003-01-01

Background Appropriate definition of neural network architecture prior to data analysis is crucial for successful data mining. This can be challenging when the underlying model of the data is unknown. The goal of this study was to determine whether optimizing neural network architecture using genetic programming as a machine learning strategy would improve the ability of neural networks to model and detect nonlinear interactions among genes in studies of common human diseases. Results Using simulated data, we show that a genetic programming optimized neural network approach is able to model gene-gene interactions as well as a traditional back propagation neural network. Furthermore, the genetic programming optimized neural network is better than the traditional back propagation neural network approach in terms of predictive ability and power to detect gene-gene interactions when non-functional polymorphisms are present. Conclusion This study suggests that a machine learning strategy for optimizing neural network architecture may be preferable to traditional trial-and-error approaches for the identification and characterization of gene-gene interactions in common, complex human diseases. PMID:12846935

Near Optimal Event-Triggered Control of Nonlinear Discrete-Time Systems Using Neurodynamic Programming.

PubMed

Sahoo, Avimanyu; Xu, Hao; Jagannathan, Sarangapani

2016-09-01

This paper presents an event-triggered near optimal control of uncertain nonlinear discrete-time systems. Event-driven neurodynamic programming (NDP) is utilized to design the control policy. A neural network (NN)-based identifier, with event-based state and input vectors, is utilized to learn the system dynamics. An actor-critic framework is used to learn the cost function and the optimal control input. The NN weights of the identifier, the critic, and the actor NNs are tuned aperiodically once every triggered instant. An adaptive event-trigger condition to decide the trigger instants is derived. Thus, a suitable number of events are generated to ensure a desired accuracy of approximation. A near optimal performance is achieved without using value and/or policy iterations. A detailed analysis of nontrivial inter-event times with an explicit formula to show the reduction in computation is also derived. The Lyapunov technique is used in conjunction with the event-trigger condition to guarantee the ultimate boundedness of the closed-loop system. The simulation results are included to verify the performance of the controller. The net result is the development of event-driven NDP.

Feedback modulation of neural network synchrony and seizure susceptibility by Mdm2-p53-Nedd4-2 signaling.

PubMed

Jewett, Kathryn A; Christian, Catherine A; Bacos, Jonathan T; Lee, Kwan Young; Zhu, Jiuhe; Tsai, Nien-Pei

2016-03-22

Neural network synchrony is a critical factor in regulating information transmission through the nervous system. Improperly regulated neural network synchrony is implicated in pathophysiological conditions such as epilepsy. Despite the awareness of its importance, the molecular signaling underlying the regulation of neural network synchrony, especially after stimulation, remains largely unknown. In this study, we show that elevation of neuronal activity by the GABA(A) receptor antagonist, Picrotoxin, increases neural network synchrony in primary mouse cortical neuron cultures. The elevation of neuronal activity triggers Mdm2-dependent degradation of the tumor suppressor p53. We show here that blocking the degradation of p53 further enhances Picrotoxin-induced neural network synchrony, while promoting the inhibition of p53 with a p53 inhibitor reduces Picrotoxin-induced neural network synchrony. These data suggest that Mdm2-p53 signaling mediates a feedback mechanism to fine-tune neural network synchrony after activity stimulation. Furthermore, genetically reducing the expression of a direct target gene of p53, Nedd4-2, elevates neural network synchrony basally and occludes the effect of Picrotoxin. Finally, using a kainic acid-induced seizure model in mice, we show that alterations of Mdm2-p53-Nedd4-2 signaling affect seizure susceptibility. Together, our findings elucidate a critical role of Mdm2-p53-Nedd4-2 signaling underlying the regulation of neural network synchrony and seizure susceptibility and reveal potential therapeutic targets for hyperexcitability-associated neurological disorders.

Neural Mechanisms of Recognizing Camouflaged Objects: A Human fMRI Study

DTIC Science & Technology

2015-07-30

Unlimited Final Report: Neural Mechanisms of Recognizing Camouflaged Objects: A Human fMRI Study The views, opinions and/or findings contained in this...27709-2211 Visual search, Camouflage, Functional magnetic resonance imaging ( fMRI ), Perceptual learning REPORT DOCUMENTATION PAGE 11. SPONSOR...ABSTRACT Number of Papers published in peer-reviewed journals: Final Report: Neural Mechanisms of Recognizing Camouflaged Objects: A Human fMRI Study

Neural conflict-control mechanisms improve memory for target stimuli.

PubMed

Krebs, Ruth M; Boehler, Carsten N; De Belder, Maya; Egner, Tobias

2015-03-01

According to conflict-monitoring models, conflict serves as an internal signal for reinforcing top-down attention to task-relevant information. While evidence based on measures of ongoing task performance supports this idea, implications for long-term consequences, that is, memory, have not been tested yet. Here, we evaluated the prediction that conflict-triggered attentional enhancement of target-stimulus processing should be associated with superior subsequent memory for those stimuli. By combining functional magnetic resonance imaging (fMRI) with a novel variant of a face-word Stroop task that employed trial-unique face stimuli as targets, we were able to assess subsequent (incidental) memory for target faces as a function of whether a given face had previously been accompanied by congruent, neutral, or incongruent (conflicting) distracters. In line with our predictions, incongruent distracters not only induced behavioral conflict, but also gave rise to enhanced memory for target faces. Moreover, conflict-triggered neural activity in prefrontal and parietal regions was predictive of subsequent retrieval success, and displayed conflict-enhanced functional coupling with medial-temporal lobe regions. These data provide support for the proposal that conflict evokes enhanced top-down attention to task-relevant stimuli, thereby promoting their encoding into long-term memory. Our findings thus delineate the neural mechanisms of a novel link between cognitive control and memory. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Neural response in obsessive-compulsive washers depends on individual fit of triggers

PubMed Central

Baioui, Ali; Pilgramm, Juliane; Merz, Christian J.; Walter, Bertram; Vaitl, Dieter; Stark, Rudolf

2013-01-01

Background: Patients with obsessive-compulsive disorder (OCD) have highly idiosyncratic triggers. To fully understand which role this idiosyncrasy plays in the neurobiological mechanisms behind OCD, it is necessary to elucidate the impact of individualization regarding the applied investigation methods. This functional magnetic resonance imaging (fMRI) study explores the neural correlates of contamination/washing-related OCD with a highly individualized symptom provocation paradigm. Additionally, it is the first study to directly compare individualized and standardized symptom provocation. Methods: Nineteen patients with washing compulsions created individual OCD hierarchies, which later served as instructions to photograph their own individualized stimulus sets. The patients and 19 case-by-case matched healthy controls participated in a symptom provocation fMRI experiment with individualized and standardized stimulus sets created for each patient. Results: OCD patients compared to healthy controls displayed stronger activation in the basal ganglia (nucleus accumbens, nucleus caudatus, pallidum) for individualized symptom provocation. Using standardized symptom provocation, this group comparison led to stronger activation in the nucleus caudatus. The direct comparison of between-group effects for both symptom provocation approaches revealed stronger activation of the orbitofronto-striatal network for individualized symptom provocation. Conclusions: The present study provides insight into the differential impact of individualized and standardized symptom provocation on the orbitofronto-striatal network of OCD washers. Behavioral and neural responses imply a higher symptom-specificity of individualized symptom provocation. PMID:23630478

From Attire to Assault: Clothing, Objectification, and De-humanization - A Possible Prelude to Sexual Violence?

PubMed

Awasthi, Bhuvanesh

2017-01-01

In the context of objectification and violence, little attention has been paid to the perception neuroscience of how the human brain perceives bodies and objectifies them. Various studies point to how external cues such as appearance and attire could play a key role in encouraging objectification, dehumanization and the denial of agency. Reviewing new experimental findings across several areas of research, it seems that common threads run through issues of clothing, sexual objectification, body perception, dehumanization, and assault. Collating findings from several different lines of research, this article reviews additional evidence from cognitive and neural dynamics of person perception (body and face perception processes) that predict downstream social behavior. Specifically, new findings demonstrate cognitive processing of sexualized female bodies as object-like, a crucial aspect of dehumanized percept devoid of agency and personhood. Sexual violence is a consequence of a dehumanized perception of female bodies that aggressors acquire through their exposure and interpretation of objectified body images. Integrating these findings and identifying triggers for sexual violence may help develop remedial measures and inform law enforcement processes and policy makers alike.

Roles of autophagy in controlling stem cell identity: a perspective of self-renewal and differentiation.

PubMed

Sotthibundhu, Areechun; Promjuntuek, Wilasinee; Liu, Min; Shen, Sanbing; Noisa, Parinya

2018-04-25

Autophagy is crucial for the removal of dysfunctional organelles and protein aggregates and for maintaining stem cell homeostasis, which includes self-renewal, cell differentiation and somatic reprogramming. Loss of self-renewal capacity and pluripotency is a major obstacle to stem cell-based therapies. It has been reported that autophagy regulates stem cells under biological stimuli, starvation, hypoxia, generation of reactive oxygen species (ROS) and cellular senescence. On the one hand, autophagy is shown to play roles in self-renewal by co-function with the ubiquitin-proteasome system (UPS) to promote pluripotency-associated proteins (NANOG, OCT4 and SOX2) in human embryonic stem cells (hESCs). On the other hand, autophagy activity acts as cell reprogramming processes that play an important role for clearance fate determination and upregulates neural and cardiac differentiation. Deregulation of autophagy triggers protein disorders such as neurodegenerative cardiac/muscle diseases and cancer. Therefore, understanding of the roles of the autophagy in stem cell renewal and differentiation may benefit therapeutic development for a range of human diseases.

From Attire to Assault: Clothing, Objectification, and De-humanization – A Possible Prelude to Sexual Violence?

PubMed Central

Awasthi, Bhuvanesh

2017-01-01

In the context of objectification and violence, little attention has been paid to the perception neuroscience of how the human brain perceives bodies and objectifies them. Various studies point to how external cues such as appearance and attire could play a key role in encouraging objectification, dehumanization and the denial of agency. Reviewing new experimental findings across several areas of research, it seems that common threads run through issues of clothing, sexual objectification, body perception, dehumanization, and assault. Collating findings from several different lines of research, this article reviews additional evidence from cognitive and neural dynamics of person perception (body and face perception processes) that predict downstream social behavior. Specifically, new findings demonstrate cognitive processing of sexualized female bodies as object-like, a crucial aspect of dehumanized percept devoid of agency and personhood. Sexual violence is a consequence of a dehumanized perception of female bodies that aggressors acquire through their exposure and interpretation of objectified body images. Integrating these findings and identifying triggers for sexual violence may help develop remedial measures and inform law enforcement processes and policy makers alike. PMID:28344565

Natural and Artificial Intelligence, Language, Consciousness, Emotion, and Anticipation

NASA Astrophysics Data System (ADS)

Dubois, Daniel M.

2010-11-01

The classical paradigm of the neural brain as the seat of human natural intelligence is too restrictive. This paper defends the idea that the neural ectoderm is the actual brain, based on the development of the human embryo. Indeed, the neural ectoderm includes the neural crest, given by pigment cells in the skin and ganglia of the autonomic nervous system, and the neural tube, given by the brain, the spinal cord, and motor neurons. So the brain is completely integrated in the ectoderm, and cannot work alone. The paper presents fundamental properties of the brain as follows. Firstly, Paul D. MacLean proposed the triune human brain, which consists to three brains in one, following the species evolution, given by the reptilian complex, the limbic system, and the neo-cortex. Secondly, the consciousness and conscious awareness are analysed. Thirdly, the anticipatory unconscious free will and conscious free veto are described in agreement with the experiments of Benjamin Libet. Fourthly, the main section explains the development of the human embryo and shows that the neural ectoderm is the whole neural brain. Fifthly, a conjecture is proposed that the neural brain is completely programmed with scripts written in biological low-level and high-level languages, in a manner similar to the programmed cells by the genetic code. Finally, it is concluded that the proposition of the neural ectoderm as the whole neural brain is a breakthrough in the understanding of the natural intelligence, and also in the future design of robots with artificial intelligence.

Sonic Hedgehog promotes the survival of neural crest cells by limiting apoptosis induced by the dependence receptor CDON during branchial arch development.

PubMed

Delloye-Bourgeois, Céline; Rama, Nicolas; Brito, José; Le Douarin, Nicole; Mehlen, Patrick

2014-09-26

Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO or CDON) was identified as a receptor for the classic morphogen Sonic Hedgehog (SHH). It has been shown that, in cell culture, CDO also behaves as a SHH dependence receptor: CDO actively triggers apoptosis in absence of SHH via a proteolytic cleavage in CDO intracellular domain. We present evidence that CDO is also pro-apoptotic in the developing neural tube where SHH is known to act as a survival factor. SHH, produced by the ventral foregut endoderm, was shown to promote survival of facial neural crest cells (NCCs) that colonize the first branchial arch (BA1). We show here that the survival activity of SHH on neural crest cells is due to SHH-mediated inhibition of CDO pro-apoptotic activity. Silencing of CDO rescued NCCs from apoptosis observed upon SHH inhibition in the ventral foregut endoderm. Thus, the pair SHH/dependence receptor CDO may play an important role in neural crest cell survival during the formation of the first branchial arch. Copyright © 2014 Elsevier Inc. All rights reserved.

Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes

PubMed Central

Hockman, Dorit; Burns, Alan J; Schlosser, Gerhard; Gates, Keith P; Jevans, Benjamin; Mongera, Alessandro; Fisher, Shannon; Unlu, Gokhan; Knapik, Ela W; Kaufman, Charles K; Mosimann, Christian; Zon, Leonard I; Lancman, Joseph J; Dong, P Duc S; Lickert, Heiko; Tucker, Abigail S; Baker, Clare V H

2017-01-01

The evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes – carotid body glomus cells, and ‘pulmonary neuroendocrine cells’ (PNECs) - are obscure. Homology has been proposed between glomus cells, which are neural crest-derived, and the hypoxia-sensitive ‘neuroepithelial cells’ (NECs) of fish gills, whose embryonic origin is unknown. NECs have also been likened to PNECs, which differentiate in situ within lung airway epithelia. Using genetic lineage-tracing and neural crest-deficient mutants in zebrafish, and physical fate-mapping in frog and lamprey, we find that NECs are not neural crest-derived, but endoderm-derived, like PNECs, whose endodermal origin we confirm. We discover neural crest-derived catecholaminergic cells associated with zebrafish pharyngeal arch blood vessels, and propose a new model for amniote hypoxia-sensitive cell evolution: endoderm-derived NECs were retained as PNECs, while the carotid body evolved via the aggregation of neural crest-derived catecholaminergic (chromaffin) cells already associated with blood vessels in anamniote pharyngeal arches. DOI: http://dx.doi.org/10.7554/eLife.21231.001 PMID:28387645

Single-site neural tube closure in human embryos revisited.

PubMed

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.

Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

2009-01-01

The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering mechanisms which surround Herpes vial reactivation and proliferation. Additionally, prolonged replication of these viruses will allow the tracking of viral genomic shift.

Development of human nervous tissue upon differentiation of embryonic stem cells in three-dimensional culture.

PubMed

Preynat-Seauve, Olivier; Suter, David M; Tirefort, Diderik; Turchi, Laurent; Virolle, Thierry; Chneiweiss, Herve; Foti, Michelangelo; Lobrinus, Johannes-Alexander; Stoppini, Luc; Feki, Anis; Dubois-Dauphin, Michel; Krause, Karl Heinz

2009-03-01

Researches on neural differentiation using embryonic stem cells (ESC) require analysis of neurogenesis in conditions mimicking physiological cellular interactions as closely as possible. In this study, we report an air-liquid interface-based culture of human ESC. This culture system allows three-dimensional cell expansion and neural differentiation in the absence of added growth factors. Over a 3-month period, a macroscopically visible, compact tissue developed. Histological coloration revealed a dense neural-like neural tissue including immature tubular structures. Electron microscopy, immunochemistry, and electrophysiological recordings demonstrated a dense network of neurons, astrocytes, and oligodendrocytes able to propagate signals. Within this tissue, tubular structures were niches of cells resembling germinal layers of human fetal brain. Indeed, the tissue contained abundant proliferating cells expressing markers of neural progenitors. Finally, the capacity to generate neural tissues on air-liquid interface differed for different ESC lines, confirming variations of their neurogenic potential. In conclusion, this study demonstrates in vitro engineering of a human neural-like tissue with an organization that bears resemblance to early developing brain. As opposed to previously described methods, this differentiation (a) allows three-dimensional organization, (b) yields dense interconnected neural tissue with structurally and functionally distinct areas, and (c) is spontaneously guided by endogenous developmental cues.

The neurophysiological and evolutionary considerations of close combat: A modular approach.

PubMed

Dervenis, Kostas; Tsialogiannis, Evangelos

2017-01-01

Close Combat may be identified as a physical confrontation involving armed or unarmed fighting, lethal and/or non-lethal methods, or even simply escape from and/or de-escalation of the confrontation. Our model hypothesizes that distinct areas of the brain are utilized for specific levels of violence, based on evolutionary criteria, and that these levels of violence bring into effect distinct physiological criteria and kinesiology. This model is outlined similar to Paul D. MacLean's triune brain theory, but incorporates distinct processes inherent to the autonomic nervous system (i.e. a "quadrune brain"), and correlates the observed level of violence to a particular response to a specific neural complex associated with very specific reactive kinesiology in the body. Our hypothesis is that the reverse also holds true: specific movements, scenarios and breathing will "activate" corresponding neural centres that in turn correlate to a respective level of violence. Moreover, socio-historic records bear out the premise that specific behavioural violations of social protocols act as "triggers" for assaultive and lethal force involving weapons, and it is very likely that these triggers (and the concomitant decision to engage in assault or lethal force) are processed through neural centres in what McLean has described as his "limbic system." A modular system of close combat is being researched and developed in accord with the above, readily adaptable to the level of violence professional peacekeepers and law enforcement officers may encounter in the course of their duties, but also directly relevant to the self-protection needs of civilians and youth. Distinct modular training regimes have been identified and developed for situations involving escape from a threat, submission of an adversary, and assaultive/lethal force, with the hope of strengthening neural bridges between the four neural complexes postulated in our model, and therefore via these bridges limiting adverse reactions to the psyche from combat stress.

Engineering Human Neural Tissue by 3D Bioprinting.

PubMed

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.

Distinct Responses of Stem Cells to Telomere Uncapping-A Potential Strategy to Improve the Safety of Cell Therapy.

PubMed

Liu, Chang Ching; Ma, Dong Liang; Yan, Ting-Dong; Fan, XiuBo; Poon, Zhiyong; Poon, Lai-Fong; Goh, Su-Ann; Rozen, Steve G; Hwang, William Ying Khee; Tergaonkar, Vinay; Tan, Patrick; Ghosh, Sujoy; Virshup, David M; Goh, Eyleen L K; Li, Shang

2016-10-01

In most human somatic cells, the lack of telomerase activity results in progressive telomere shortening during each cell division. Eventually, DNA damage responses triggered by critically short telomeres induce an irreversible cell cycle arrest termed replicative senescence. However, the cellular responses of human pluripotent stem cells to telomere uncapping remain unknown. We generated telomerase knockout human embryonic stem (ES) cells through gene targeting. Telomerase inactivation in ES cells results in progressive telomere shortening. Telomere DNA damage in ES cells and neural progenitor cells induces rapid apoptosis when telomeres are uncapped, in contrast to fibroblast cells that enter a state of replicative senescence. Significantly, telomerase inactivation limits the proliferation capacity of human ES cells without affecting their pluripotency. By targeting telomerase activity, we can functionally separate the two unique properties of human pluripotent stem cells, namely unlimited self-renewal and pluripotency. We show that the potential of ES cells to form teratomas in vivo is dictated by their telomere length. By controlling telomere length of ES cells through telomerase inactivation, we can inhibit teratoma formation and potentially improve the safety of cell therapies involving terminally differentiated cells as well as specific progenitor cells that do not require sustained cellular proliferation in vivo, and thus sustained telomerase activity. Stem Cells 2016;34:2471-2484. © 2016 AlphaMed Press.

Invariant recognition drives neural representations of action sequences

PubMed Central

Poggio, Tomaso

2017-01-01

Recognizing the actions of others from visual stimuli is a crucial aspect of human perception that allows individuals to respond to social cues. Humans are able to discriminate between similar actions despite transformations, like changes in viewpoint or actor, that substantially alter the visual appearance of a scene. This ability to generalize across complex transformations is a hallmark of human visual intelligence. Advances in understanding action recognition at the neural level have not always translated into precise accounts of the computational principles underlying what representations of action sequences are constructed by human visual cortex. Here we test the hypothesis that invariant action discrimination might fill this gap. Recently, the study of artificial systems for static object perception has produced models, Convolutional Neural Networks (CNNs), that achieve human level performance in complex discriminative tasks. Within this class, architectures that better support invariant object recognition also produce image representations that better match those implied by human and primate neural data. However, whether these models produce representations of action sequences that support recognition across complex transformations and closely follow neural representations of actions remains unknown. Here we show that spatiotemporal CNNs accurately categorize video stimuli into action classes, and that deliberate model modifications that improve performance on an invariant action recognition task lead to data representations that better match human neural recordings. Our results support our hypothesis that performance on invariant discrimination dictates the neural representations of actions computed in the brain. These results broaden the scope of the invariant recognition framework for understanding visual intelligence from perception of inanimate objects and faces in static images to the study of human perception of action sequences. PMID:29253864

An improved protocol that induces human embryonic stem cells to differentiate into neural cells in vitro.

PubMed

Zhou, Jun-Mei; Chu, Jian-Xin; Chen, Xue-Jin

2008-01-01

Human embryonic stem (ES) cells have the capacity for self-renewal and are able to differentiate into any cell type. However, obtaining high-efficient neural differentiation from human ES cells remains a challenge. This study describes an improved 4-stage protocol to induce a human ES cell line derived from a Chinese population to differentiate into neural cells. At the first stage, embryonic bodies (EBs) were formed in a chemically-defined neural inducing medium rather than in traditional serum or serum-replacement medium. At the second stage, rosette-like structures were formed. At the third stage, the rosette-like structures were manually selected rather than enzymatically digested to form floating neurospheres. At the fourth stage, the neurospheres were further differentiated into neurons. The results show that, at the second stage, the rate of the formation of rosette-like structures from EBs induced by noggin was 88+/-6.32%, higher than that of retinoic acid 55+/-5.27%. Immunocytochemistry staining was used to confirm the neural identity of the cells. These results show a major improvement in obtaining efficient neural differentiation of human ES cells.

Behavioral methods to study anxiety in rodents

PubMed Central

Lezak, Kimberly R.; Missig, Galen; Carlezon Jr, William A.

2017-01-01

Stress is a precipitating factor for anxiety-related disorders, which are among the leading forms of psychiatric illness and impairment in the modern world. Rodent-based behavioral tests and models are widely used to understand the mechanisms by which stress triggers anxiety-related behaviors and to identify new treatments for anxiety-related disorders. Although substantial progress has been made and many of the key neural circuits and molecular pathways mediating stress responsiveness have been characterized, these advances have thus far failed to translate into fundamentally new treatments that are safer and more efficacious in humans. The purpose of this article is to describe methods that have been historically used for this type of research and to highlight new approaches that align with recent conceptualizations of disease symptomatology and that may ultimately prove to be more fruitful in facilitating the development of improved therapeutics. PMID:28867942

Processing of social and monetary rewards in the human striatum.

PubMed

Izuma, Keise; Saito, Daisuke N; Sadato, Norihiro

2008-04-24

Despite an increasing focus on the neural basis of human decision making in neuroscience, relatively little attention has been paid to decision making in social settings. Moreover, although human social decision making has been explored in a social psychology context, few neural explanations for the observed findings have been considered. To bridge this gap and improve models of human social decision making, we investigated whether acquiring a good reputation, which is an important incentive in human social behaviors, activates the same reward circuitry as monetary rewards. In total, 19 subjects participated in functional magnetic resonance imaging (fMRI) experiments involving monetary and social rewards. The acquisition of one's good reputation robustly activated reward-related brain areas, notably the striatum, and these overlapped with the areas activated by monetary rewards. Our findings support the idea of a "common neural currency" for rewards and represent an important first step toward a neural explanation for complex human social behaviors.

A Study for the Feature Selection to Identify GIEMSA-Stained Human Chromosomes Based on Artificial Neural Network

DTIC Science & Technology

2001-10-25

neural network (ANN) has been adopted for the human chromosome classification. It is important to select optimum features for training neural network...Many studies for computer-based chromosome analysis have shown that it is possible to classify chromosomes into 24 subgroups. In addition, artificial

The Neural Representations Underlying Human Episodic Memory.

PubMed

Xue, Gui

2018-06-01

A fundamental question of human episodic memory concerns the cognitive and neural representations and processes that give rise to the neural signals of memory. By integrating behavioral tests, formal computational models, and neural measures of brain activity patterns, recent studies suggest that memory signals not only depend on the neural processes and representations during encoding and retrieval, but also on the interaction between encoding and retrieval (e.g., transfer-appropriate processing), as well as on the interaction between the tested events and all other events in the episodic memory space (e.g., global matching). In addition, memory signals are also influenced by the compatibility of the event with the existing long-term knowledge (e.g., schema matching). These studies highlight the interactive nature of human episodic memory. Copyright © 2018 Elsevier Ltd. All rights reserved.

Frequency modulation entrains slow neural oscillations and optimizes human listening behavior

PubMed Central

Henry, Molly J.; Obleser, Jonas

2012-01-01

The human ability to continuously track dynamic environmental stimuli, in particular speech, is proposed to profit from “entrainment” of endogenous neural oscillations, which involves phase reorganization such that “optimal” phase comes into line with temporally expected critical events, resulting in improved processing. The current experiment goes beyond previous work in this domain by addressing two thus far unanswered questions. First, how general is neural entrainment to environmental rhythms: Can neural oscillations be entrained by temporal dynamics of ongoing rhythmic stimuli without abrupt onsets? Second, does neural entrainment optimize performance of the perceptual system: Does human auditory perception benefit from neural phase reorganization? In a human electroencephalography study, listeners detected short gaps distributed uniformly with respect to the phase angle of a 3-Hz frequency-modulated stimulus. Listeners’ ability to detect gaps in the frequency-modulated sound was not uniformly distributed in time, but clustered in certain preferred phases of the modulation. Moreover, the optimal stimulus phase was individually determined by the neural delta oscillation entrained by the stimulus. Finally, delta phase predicted behavior better than stimulus phase or the event-related potential after the gap. This study demonstrates behavioral benefits of phase realignment in response to frequency-modulated auditory stimuli, overall suggesting that frequency fluctuations in natural environmental input provide a pacing signal for endogenous neural oscillations, thereby influencing perceptual processing. PMID:23151506

Preclinical Analysis of Fetal Human Mesencephalic Neural Progenitor Cell Lines: Characterization and Safety In Vitro and In Vivo

PubMed Central

Moon, Jisook; Schwarz, Sigrid C.; Lee, Hyun‐Seob; Kang, Jun Mo; Lee, Young‐Eun; Kim, Bona; Sung, Mi‐Young; Höglinger, Günter; Wegner, Florian; Kim, Jin Su; Chung, Hyung‐Min; Chang, Sung Woon; Cha, Kwang Yul; Kim, Kwang‐Soo

2016-01-01

Abstract We have developed a good manufacturing practice for long‐term cultivation of fetal human midbrain‐derived neural progenitor cells. The generation of human dopaminergic neurons may serve as a tool of either restorative cell therapies or cellular models, particularly as a reference for phenotyping region‐specific human neural stem cell lines such as human embryonic stem cells and human inducible pluripotent stem cells. We cultivated 3 different midbrain neural progenitor lines at 10, 12, and 14 weeks of gestation for more than a year and characterized them in great detail, as well as in comparison with Lund mesencephalic cells. The whole cultivation process of tissue preparation, cultivation, and cryopreservation was developed using strict serum‐free conditions and standardized operating protocols under clean‐room conditions. Long‐term‐cultivated midbrain‐derived neural progenitor cells retained stemness, midbrain fate specificity, and floorplate markers. The potential to differentiate into authentic A9‐specific dopaminergic neurons was markedly elevated after prolonged expansion, resulting in large quantities of functional dopaminergic neurons without genetic modification. In restorative cell therapeutic approaches, midbrain‐derived neural progenitor cells reversed impaired motor function in rodents, survived well, and did not exhibit tumor formation in immunodeficient nude mice in the short or long term (8 and 30 weeks, respectively). We conclude that midbrain‐derived neural progenitor cells are a promising source for human dopaminergic neurons and suitable for long‐term expansion under good manufacturing practice, thus opening the avenue for restorative clinical applications or robust cellular models such as high‐content or high‐throughput screening. Stem Cells Translational Medicine 2017;6:576–588 PMID:28191758

Learning and adaptation: neural and behavioural mechanisms behind behaviour change

NASA Astrophysics Data System (ADS)

Lowe, Robert; Sandamirskaya, Yulia

2018-01-01

This special issue presents perspectives on learning and adaptation as they apply to a number of cognitive phenomena including pupil dilation in humans and attention in robots, natural language acquisition and production in embodied agents (robots), human-robot game play and social interaction, neural-dynamic modelling of active perception and neural-dynamic modelling of infant development in the Piagetian A-not-B task. The aim of the special issue, through its contributions, is to highlight some of the critical neural-dynamic and behavioural aspects of learning as it grounds adaptive responses in robotic- and neural-dynamic systems.

Human Fetal Keratocytes Have Multipotent Characteristics in the Developing Avian Embryo

PubMed Central

Chao, Jennifer R.; Bronner, Marianne E.

2013-01-01

The human cornea contains stem cells that can be induced to express markers consistent with multipotency in cell culture; however, there have been no studies demonstrating that human corneal keratocytes are multipotent. The objective of this study is to examine the potential of human fetal keratocytes (HFKs) to differentiate into neural crest-derived tissues when challenged in an embryonic environment. HFKs were injected bilaterally into the cranial mesenchyme adjacent to the neural tube and the periocular mesenchyme in chick embryos at embryonic days 1.5 and 3, respectively. The injected keratocytes were detected by immunofluorescence using the human cell-specific marker, HuNu. HuNu-positive keratocytes injected along the neural crest pathway were localized adjacent to HNK-1-positive migratory host neural crest cells and in the cardiac cushion mesenchyme. The HuNu-positive cells transformed into neural crest derivatives such as smooth muscle in cranial blood vessels, stromal keratocytes, and corneal endothelium. However, they failed to form neurons despite their presence in the condensing trigeminal ganglion. These results show that HFKs retain the ability to differentiate into some neural crest-derived tissues. Their ability to respond to embryonic cues and generate corneal endothelium and stromal keratocytes provides a basis for understanding the feasibility of creating specialized cells for possible use in regenerative medicine. PMID:23461574

6-mercaptopurine (6-MP) induces p53-mediated apoptosis of neural progenitor cells in the developing fetal rodent brain.

PubMed

Kanemitsu, H; Yamauchi, H; Komatsu, M; Yamamoto, S; Okazaki, S; Uchida, K; Nakayama, H

2009-01-01

6-mercaptopurine (6-MP), a DNA-damaging agent, induces apoptosis of neural progenitor cells, and causes malformation in the fetal brain. The aim of the present study is to clarify the molecular pathway of 6-MP-induced apoptosis of neural progenitor cells in the fetal telencephalon of rats and mice. p53 protein is activated by DNA damage and induces apoptosis through either the intrinsic pathway involving the mitochondria or the extrinsic pathway triggered by death receptors. In this study, the expression of puma and cleaved caspase-9 proteins, which are specific intrinsic pathway factors, increased in the rat telencephalon after 6-MP treatment. 6-MP-induced apoptosis of neural progenitor cells was completely absent in p53-deficient mice. On the other hand, the expression of Fas protein, an extrinsic pathway factor, did not change throughout the experimental period in the rat telencephalon treated with 6-MP. The number of apoptotic neural progenitor cells was similar among Fas-mutated lpr/lpr and wild-type mice, suggesting that the Fas pathway does not play a significant role in 6-MP-induced apoptosis of neural progenitor cells. These results may suggest that the p53-mediated intrinsic pathway is essential for 6-MP-induced apoptosis of neural progenitor cells in the developing telencephalon of rats and mice.

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

PubMed Central

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

Top-Down Inhibition of BMP Signaling Enables Robust Induction of hPSCs Into Neural Crest in Fully Defined, Xeno-free Conditions.

PubMed

Hackland, James O S; Frith, Tom J R; Thompson, Oliver; Marin Navarro, Ana; Garcia-Castro, Martin I; Unger, Christian; Andrews, Peter W

2017-10-10

Defects in neural crest development have been implicated in many human disorders, but information about human neural crest formation mostly depends on extrapolation from model organisms. Human pluripotent stem cells (hPSCs) can be differentiated into in vitro counterparts of the neural crest, and some of the signals known to induce neural crest formation in vivo are required during this process. However, the protocols in current use tend to produce variable results, and there is no consensus as to the precise signals required for optimal neural crest differentiation. Using a fully defined culture system, we have now found that the efficient differentiation of hPSCs to neural crest depends on precise levels of BMP signaling, which are vulnerable to fluctuations in endogenous BMP production. We present a method that controls for this phenomenon and could be applied to other systems where endogenous signaling can also affect the outcome of differentiation protocols. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Neural correlates of individual differences in anxiety sensitivity: an fMRI study using semantic priming.

PubMed

Yang, Yunbo; Lueken, Ulrike; Wittmann, André; Holtz, Katharina; Kleint, Nina Isabel; Herrmann, Martin J; Sass, Katharina; Jansen, Andreas; Konrad, Carsten; Ströhle, Andreas; Pfleiderer, Bettina; Lotze, Martin; Hamm, Alfons; Deckert, Jürgen; Arolt, Volker; Wittchen, Hans-Ulrich; Kircher, Tilo; Straube, Benjamin

2016-08-01

Individuals with high anxiety sensitivity (AS) have an increased risk of developing anxiety disorders and are more biased in how they process fear-related stimuli. This study investigates the neural correlates of fear-related words and word associations in high- and low-AS individuals. We used a semantic priming paradigm during functional magnetic resonance imaging in which three types of target words (fear symptoms, e.g. 'dizziness'; neutral, e.g. 'drink'; and pseudowords, e.g. 'salkom') were preceded by two types of prime words (fear-triggers, e.g. 'elevator'; and neutral, e.g. 'bottle'). Subjects with high AS rated fear-symptom words (vs neutral words) as more unpleasant than low-AS individuals; they also related these words more strongly to fear-triggers and showed prolonged reaction times. During the processing of fear-symptom words, greater activation in the left anterior insula was observed in high-AS subjects than in low-AS subjects. Lower activation in the left inferior frontal gyrus, angular gyrus, fusiform gyrus and bilateral amygdalae was found in high-AS subjects when fear-symptom words were preceded by fear-trigger words. The findings suggest that cognitive biases and the anterior insula play a crucial role in high-AS individuals. Furthermore, semantic processes may contribute to high AS and the risk of developing anxiety disorders. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Social Isolation Co-opts Fear and Aggression Circuits.

PubMed

Rodriguez-Romaguera, Jose; Stuber, Garret D

2018-05-17

Social isolation is a stressful condition that often leads to maladaptive behaviors. In this issue of Cell, Zelikowsky et al. find that chronic social isolation stress triggers an increase in neuronal tachykinin signaling across distinct brain regions that mediate fear and aggression, elucidating the neural basis of these maladaptive responses. Copyright © 2018. Published by Elsevier Inc.

Neural crest cells: from developmental biology to clinical interventions.

PubMed

Noisa, Parinya; Raivio, Taneli

2014-09-01

Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc.

Sex differences in associations between cannabis craving and neural responses to cannabis cues: Implications for treatment.

PubMed

Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Franklin, Teresa R

2015-08-01

Preclinical and clinical research indicates that there are sex differences in how men and women initiate, progress, respond to, and withdraw from cannabis use; however, neurophysiological differences, such as neural responses to cannabis cues, are not well understood. Using functional MRI and an event-related blood oxygen level-dependent backward-masking task, we compared neural responses to backward-masked cannabis cues to neutral cues in treatment-seeking, cannabis-dependent adults (N = 44; 27 males) and examined whether sex differences exist. In addition, functional MRI findings were correlated with cannabis craving. Backward-masked cannabis cues elicited greater neural responses than neutral cues in reward-related brain regions, including the striatum, hippocampus/amygdala, insula, anterior cingulate cortex, and lateral orbitofrontal cortex, p < .01, k > 121 voxels. Although no significant sex differences in neural responses to cannabis cues emerged, women showed a positive correlation between neural responses to cannabis cues in the bilateral insula and cannabis craving and an inverse correlation between neural responses to cannabis cues in the left lateral orbitofrontal cortex and cannabis craving. Men, however, showed a positive correlation between neural responses to cannabis cues in the striatum and cannabis craving. Given that cues and craving are important triggers and the focus on many behavioral treatment approaches, these findings suggest that treatment-seeking, cannabis-dependent men and women may benefit from sex-specific and tailored cannabis use disorder treatments. (c) 2015 APA, all rights reserved).

An Exploratory Study to Determine the Relationship between Cervical Dysfunction and Perimenstrual Migraines

PubMed Central

Horwitz, Simone

2015-01-01

ABSTRACT Purpose: To determine whether an association between cervical dysfunction and perimenstrual migraines exists. Methods: Forty perimenstrual migraine sufferers and 46 controls were compared. Information on the participants' ages and perceptions of neck pain and stiffness were solicited. The blinded physical examination of the cervical area consisted of postural, range of motion, muscle strength, muscle length, trigger point, neural mobility, and segmental cervical joint movement assessment. Results: The migraine group had increased perception of neck pain and stiffness (p<0.001); reduced bilateral rotation (p=0.013); decreased muscle length in both trapezii, left sternocleidomastoid, and right occipitals (p=0.045); more pain on muscle stretch in both levator scapulae, both trapezii, left sternocleidomastoid, and both occipitals (p=0.013); increased trigger points bilaterally in the left trapezius (p=0.021), right trapezius (p=0.023), left sternocleidomastoid (p=0.0.004), and right sternocleidomastoid (p=0.021); reduced neural mobility with bilateral elbow lag (p=0.043); greater C4–C6 pain (p=0.045); and increased cervical stiffness in C5–C7 (p=0.023). There were no differences in posture and muscle strength. Decreased muscle length increased the risk of perimenstrual migraines 2.4–6.7 fold, reduced neural mobility 5.8–10.7 fold, and increased C7 stiffness 17.0 fold. Conclusion: The results suggest that an association between cervical dysfunction and perimenstrual headaches should be further explored. PMID:25931651

Plant chimeric Ca2+/Calmodulin-dependent protein kinase. Role of the neural visinin-like domain in regulating autophosphorylation and calmodulin affinity

NASA Technical Reports Server (NTRS)

Sathyanarayanan, P. V.; Cremo, C. R.; Poovaiah, B. W.

2000-01-01

Chimeric Ca(2+)/calmodulin-dependent protein kinase (CCaMK) is characterized by a serine-threonine kinase domain, an autoinhibitory domain, a calmodulin-binding domain and a neural visinin-like domain with three EF-hands. The neural visinin-like Ca(2+)-binding domain at the C-terminal end of the CaM-binding domain makes CCaMK unique among all the known calmodulin-dependent kinases. Biological functions of the plant visinin-like proteins or visinin-like domains in plant proteins are not well known. Using EF-hand deletions in the visinin-like domain, we found that the visinin-like domain regulated Ca(2+)-stimulated autophosphorylation of CCaMK. To investigate the effects of Ca(2+)-stimulated autophosphorylation on the interaction with calmodulin, the equilibrium binding constants of CCaMK were measured by fluorescence emission anisotropy using dansylated calmodulin. Binding was 8-fold tighter after Ca(2+)-stimulated autophosphorylation. This shift in affinity did not occur in CCaMK deletion mutants lacking Ca(2+)-stimulated autophosphorylation. A variable calmodulin affinity regulated by Ca(2+)-stimulated autophosphorylation mediated through the visinin-like domain is a new regulatory mechanism for CCaMK activation and calmodulin-dependent protein kinases. Our experiments demonstrate the existence of two functional molecular switches in a protein kinase regulating the kinase activity, namely a visinin-like domain acting as a Ca(2+)-triggered switch and a CaM-binding domain acting as an autophosphorylation-triggered molecular switch.

Siblings in Kars, Turkey, with Uner Tan syndrome (quadrupedal locomotion, severe mental retardation, and no speech): a novel theory for the evolution of human bipedalism.

PubMed

Tan, Uner

2015-02-01

To investigate siblings from Kars (n  =  2), Turkey, with diagonal-sequence quadrupedal locomotion (QL), severe mental retardation, and no speech (Uner Tan syndrome, UTS), in relation to the evolutionary emergence of human bipedal locomotion (BL). Video recordings were made to assess gaits. Brain MRI scanning was performed to visualize the cerebro-cerebellar malformations. Genome-wide association analyses were performed in venous blood samples. One of the two men with UTS showed early-onset QL and late-onset BL without infantile hypotonia, the other consistent QL with infantile hypotonia. No homozygosity was found in the genetic analysis. The family lived under extremely poor socioeconomic conditions. Low socioeconomic status may be a triggering factor for the epigenetic emergence of UTS. The neural networks responsible for the ancestral diagonal-sequence QL, evolutionarily preserved since about 400 MYA, may be selected during locomotor development, under the influence of self-organizing processes during pre- and postnatal periods. The diagonal-sequence QL induced ipsilateral limb interference in UTS cases as in nonhuman primates. To overcome this condition, our ancestors would prefer the attractor BL. This novel theory for the evolution of human bipedalism was evaluated in light of dynamical systems theory.

Dreaming of a Learning Task is Associated with Enhanced Sleep-Dependent Memory Consolidation

PubMed Central

Wamsley, Erin J.; Tucker, Matthew; Payne, Jessica D.; Benavides, Joseph; Stickgold, Robert

2010-01-01

Summary It is now well established that post-learning sleep is beneficial for human memory performance [1–5]. Meanwhile, human and animal studies demonstrate that learning-related neural activity is re-expressed during post-training non-rapid eye movement sleep (NREM) [6–9]. NREM sleep processes appear to be particularly beneficial for hippocampus-dependent forms of memory [1–3, 10]. These observations suggest that learning triggers the reactivation and reorganization of memory traces during sleep, a systems-level process that in turn enhances behavioral performance. Here, we hypothesized that dreaming about a learning experience during NREM sleep would be associated with improved performance on a hippocampus-dependent spatial memory task. Subjects (n=99) were trained on a virtual navigation task, and then retested on the same task 5 hours after initial training. Improved performance at retest was strongly associated with task-related dream imagery during an intervening afternoon nap. Task-related thoughts during wakefulness, in contrast, did not predict improved performance. These observations suggest that sleep-dependent memory consolidation in humans is facilitated by the offline reactivation of recently formed memories, and furthermore, that dream experiences reflect this memory processing. That similar effects were not seen during wakefulness suggests that these mnemonic processes are specific to the sleep state. PMID:20417102

Human‐Like Sensing and Reflexes of Graphene‐Based Films

PubMed Central

Zhang, Qin; Tan, Lifang; Chen, Yunxu; Zhang, Tao; Wang, Wenjie; Liu, Zhongfan

2016-01-01

Humans have numerous senses, wherein vision, hearing, smell, taste, and touch are considered as the five conventionally acknowledged senses. Triggered by light, sound, or other physical stimulations, the sensory organs of human body are excited, leading to the transformation of the afferent energy into neural activity. Also converting other signals into electronical signals, graphene‐based film shows its inherent advantages in responding to the tiny stimulations. In this review, the human‐like senses and reflexes of graphene‐based films are presented. The review starts with the brief discussions about the preparation and optimization of graphene‐based film, as where as its new progress in synthesis method, transfer operation, film‐formation technologies and optimization techniques. Various human‐like senses of graphene‐based film and their recent advancements are then summarized, including light‐sensitive devices, acoustic devices, gas sensors, biomolecules and wearable devices. Similar to the reflex action of humans, graphene‐based film also exhibits reflex when under thermal radiation and light actuation. Finally, the current challenges associated with human‐like applications are discussed to help guide the future research on graphene films. At last, the future opportunities lie in the new applicable human‐like senses and the integration of multiple senses that can raise a revolution in bionic devices. PMID:27981005

Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity.

PubMed

Azim, Kasum; Angonin, Diane; Marcy, Guillaume; Pieropan, Francesca; Rivera, Andrea; Donega, Vanessa; Cantù, Claudio; Williams, Gareth; Berninger, Benedikt; Butt, Arthur M; Raineteau, Olivier

2017-03-01

Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ) is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs) and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells originating from the SVZ. Next, we used a novel in silico genomic analysis, searchable platform-independent expression database/connectivity map (SPIED/CMAP), to generate a catalogue of small molecules that can be used to manipulate SVZ microdomain-specific lineages. Finally, we demonstrate that compounds identified in this analysis promote the generation of specific cell lineages from NSCs in vivo, during postnatal life and adulthood, as well as in regenerative contexts. This study unravels new strategies for using small bioactive molecules to direct germinal activity in the SVZ, which has therapeutic potential in neurodegenerative diseases.

Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning.

PubMed

Xu, Tao; Xiao, Na; Zhai, Xiaolong; Kwan Chan, Pak; Tin, Chung

2018-02-01

Damage to the brain, as a result of various medical conditions, impacts the everyday life of patients and there is still no complete cure to neurological disorders. Neuroprostheses that can functionally replace the damaged neural circuit have recently emerged as a possible solution to these problems. Here we describe the development of a real-time cerebellar neuroprosthetic system to substitute neural function in cerebellar circuitry for learning delay eyeblink conditioning (DEC). The system was empowered by a biologically realistic spiking neural network (SNN) model of the cerebellar neural circuit, which considers the neuronal population and anatomical connectivity of the network. The model simulated synaptic plasticity critical for learning DEC. This SNN model was carefully implemented on a field programmable gate array (FPGA) platform for real-time simulation. This hardware system was interfaced in in vivo experiments with anesthetized rats and it used neural spikes recorded online from the animal to learn and trigger conditioned eyeblink in the animal during training. This rat-FPGA hybrid system was able to process neuronal spikes in real-time with an embedded cerebellum model of ~10 000 neurons and reproduce learning of DEC with different inter-stimulus intervals. Our results validated that the system performance is physiologically relevant at both the neural (firing pattern) and behavioral (eyeblink pattern) levels. This integrated system provides the sufficient computation power for mimicking the cerebellar circuit in real-time. The system interacts with the biological system naturally at the spike level and can be generalized for including other neural components (neuron types and plasticity) and neural functions for potential neuroprosthetic applications.

Role of the medial prefrontal cortex in cataplexy.

PubMed

Oishi, Yo; Williams, Rhiannan H; Agostinelli, Lindsay; Arrigoni, Elda; Fuller, Patrick M; Mochizuki, Takatoshi; Saper, Clifford B; Scammell, Thomas E

2013-06-05

Narcolepsy is characterized by chronic sleepiness and cataplexy, episodes of profound muscle weakness that are often triggered by strong, positive emotions. Narcolepsy with cataplexy is caused by a loss of orexin (also known as hypocretin) signaling, but almost nothing is known about the neural mechanisms through which positive emotions trigger cataplexy. Using orexin knock-out mice as a model of narcolepsy, we found that palatable foods, especially chocolate, markedly increased cataplexy and activated neurons in the medial prefrontal cortex (mPFC). Reversible suppression of mPFC activity using an engineered chloride channel substantially reduced cataplexy induced by chocolate but did not affect spontaneous cataplexy. In addition, neurons in the mPFC innervated parts of the amygdala and lateral hypothalamus that contain neurons active during cataplexy and that innervate brainstem regions known to regulate motor tone. These observations indicate that the mPFC is a critical site through which positive emotions trigger cataplexy.

Role of the medial prefrontal cortex in cataplexy

PubMed Central

Oishi, Yo; Williams, Rhiannan H.; Agostinelli, Lindsay; Arrigoni, Elda; Fuller, Patrick M.; Mochizuki, Takatoshi; Saper, Clifford B.; Scammell, Thomas E.

2013-01-01

Narcolepsy is characterized by chronic sleepiness and cataplexy - episodes of profound muscle weakness that are often triggered by strong, positive emotions. Narcolepsy with cataplexy is caused by a loss of orexin (also known as hypocretin) signaling, but almost nothing is known about the neural mechanisms through which positive emotions trigger cataplexy. Using orexin knockout mice as a model of narcolepsy, we found that palatable foods, especially chocolate, markedly increased cataplexy and activated neurons in the medial prefrontal cortex (mPFC). Reversible suppression of mPFC activity using an engineered chloride channel substantially reduced cataplexy induced by chocolate but did not affect spontaneous cataplexy. In addition, neurons in the mPFC innervated parts of the amygdala and lateral hypothalamus that contain neurons active during cataplexy, and that innervate brainstem regions known to regulate motor tone. These observations indicate that the mPFC is a critical site through which positive emotions trigger cataplexy. PMID:23739971

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

PubMed

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.

Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues

PubMed Central

Coste, Cécile; Neirinckx, Virginie; Sharma, Anil; Agirman, Gulistan; Rogister, Bernard; Foguenne, Jacques; Lallemend, François

2017-01-01

Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN+ / SOX9+ / TWIST+ / SLUG+ / P75NTR+ / BRN3A+/ MSI1+/ SNAIL1+ cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow. PMID:28683107

DNA methylation regulates gabrb2 mRNA expression: developmental variations and disruptions in l-methionine-induced zebrafish with schizophrenia-like symptoms.

PubMed

Wang, L; Jiang, W; Lin, Q; Zhang, Y; Zhao, C

2016-11-01

Single nucleotide polymorphisms (SNPs) in the human type A gamma-aminobutyric acid (GABA) receptor β 2 subunit gene (GABRB2) have been associated with schizophrenia and quantitatively correlated with mRNA expression in the postmortem brain tissue of patients with schizophrenia. l-Methionine (MET) administration has been reported to cause a recrudescence of psychotic symptoms in patients with schizophrenia, and similar symptoms have been generated in MET-induced mice. In this study, a zebrafish animal model was used to evaluate the relationship between the gabrb2 mRNA expression and its promoter DNA methylation in developmental and MET-induced schizophrenia-like zebrafish. The results indicated developmental increases in global DNA methylation and decreases in gabrb2 promoter methylation in zebrafish. A significant increase in gabrb2 mRNA levels was observed after GABA was synthesized. Additionally, the MET-triggered schizophrenia-like symptoms in adult zebrafish, involving social withdrawal and cognitive dysfunction analyzed with social interaction and T-maze behavioral tests, were accompanied by significantly increased DNA methylation levels in the global genome and the gabrb2 promoter. Furthermore, the significant correlation between gabrb2 mRNA expression and gabrb2 promoter methylation observed in the developmental stages became non-significant in MET-triggered adult zebrafish. These findings demonstrate that gabrb2 mRNA expression is associated with DNA methylation varies by developmental stage and show that these epigenetic association mechanisms are disrupted in MET-triggered adult zebrafish with schizophrenia-like symptoms. In conclusion, these results provide plausible epigenetic evidence of the GABA A receptor β 2 subunit involvement in the schizophrenia-like behaviors and demonstrate the potential use of zebrafish models in neuropsychiatric research. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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

PubMed

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

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. 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. 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. 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.

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

NASA Astrophysics Data System (ADS)

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.

Transplantation of neurons derived from human iPS cells cultured on collagen matrix into guinea-pig cochleae.

PubMed

Ishikawa, Masaaki; Ohnishi, Hiroe; Skerleva, Desislava; Sakamoto, Tatsunori; Yamamoto, Norio; Hotta, Akitsu; Ito, Juichi; Nakagawa, Takayuki

2017-06-01

The present study examined the efficacy of a neural induction method for human induced pluripotent stem (iPS) cells to eliminate undifferentiated cells and to determine the feasibility of transplanting neurally induced cells into guinea-pig cochleae for replacement of spiral ganglion neurons (SGNs). A stepwise method for differentiation of human iPS cells into neurons was used. First, a neural induction method was established on Matrigel-coated plates; characteristics of cell populations at each differentiation step were assessed. Second, neural stem cells were differentiated into neurons on a three-dimensional (3D) collagen matrix, using the same protocol of culture on Matrigel-coated plates; neuron subtypes in differentiated cells on a 3D collagen matrix were examined. Then, human iPS cell-derived neurons cultured on a 3D collagen matrix were transplanted into intact guinea-pig cochleae, followed by histological analysis. In vitro analyses revealed successful induction of neural stem cells from human iPS cells, with no retention of undifferentiated cells expressing OCT3/4. After the neural differentiation of neural stem cells, approximately 70% of cells expressed a neuronal marker, 90% of which were positive for vesicular glutamate transporter 1 (VGLUT1). The expression pattern of neuron subtypes in differentiated cells on a 3D collagen matrix was identical to that of the differentiated cells on Matrigel-coated plates. In addition, the survival of transplant-derived neurons was achieved when inflammatory responses were appropriately controlled. Our preparation method for human iPS cell-derived neurons efficiently eliminated undifferentiated cells and contributed to the settlement of transplant-derived neurons expressing VGLUT1 in guinea-pig cochleae. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Study of the neural dynamics for understanding communication in terms of complex hetero systems.

PubMed

Tsuda, Ichiro; Yamaguchi, Yoko; Hashimoto, Takashi; Okuda, Jiro; Kawasaki, Masahiro; Nagasaka, Yasuo

2015-01-01

The purpose of the research project was to establish a new research area named "neural information science for communication" by elucidating its neural mechanism. The research was performed in collaboration with applied mathematicians in complex-systems science and experimental researchers in neuroscience. The project included measurements of brain activity during communication with or without languages and analyses performed with the help of extended theories for dynamical systems and stochastic systems. The communication paradigm was extended to the interactions between human and human, human and animal, human and robot, human and materials, and even animal and animal. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Implantable optoelectronic probes for in vivo optogenetics.

PubMed

Iseri, Ege; Kuzum, Duygu

2017-06-01

More than a decade has passed since optics and genetics came together and lead to the emerging technologies of optogenetics. The advent of light-sensitive opsins made it possible to optically trigger the neurons into activation or inhibition by using visible light. The importance of spatiotemporally isolating a segment of a neural network and controlling nervous signaling in a precise manner has driven neuroscience researchers and engineers to invest great efforts in designing high precision in vivo implantable devices. These efforts have focused on delivery of sufficient power to deep brain regions, while monitoring neural activity with high resolution and fidelity. In this review, we report the progress made in the field of hybrid optoelectronic neural interfaces that combine optical stimulation with electrophysiological recordings. Different approaches that incorporate optical or electrical components on implantable devices are discussed in detail. Advantages of various different designs as well as practical and fundamental limitations are summarized to illuminate the future of neurotechnology development.

A Targeted Attack For Enhancing Resiliency of Intelligent Intrusion Detection Modules in Energy Cyber Physical Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Youssef, Tarek; El Hariri, Mohammad; Habib, Hani

Abstract— Secure high-speed communication is required to ensure proper operation of complex power grid systems and prevent malicious tampering activities. In this paper, artificial neural networks with temporal dependency are introduced for false data identification and mitigation for broadcasted IEC 61850 SMV messages. The fast responses of such intelligent modules in intrusion detection make them suitable for time- critical applications, such as protection. However, care must be taken in selecting the appropriate intelligence model and decision criteria. As such, this paper presents a customizable malware script to sniff and manipulate SMV messages and demonstrates the ability of the malware tomore » trigger false positives in the neural network’s response. The malware developed is intended to be as a vaccine to harden the intrusion detection system against data manipulation attacks by enhancing the neural network’s ability to learn and adapt to these attacks.« less

Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

PubMed Central

Garza-Lombó, Carla; Gonsebatt, María E.

2016-01-01

The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

Evidence for a neural law of effect.

PubMed

Athalye, Vivek R; Santos, Fernando J; Carmena, Jose M; Costa, Rui M

2018-03-02

Thorndike's law of effect states that actions that lead to reinforcements tend to be repeated more often. Accordingly, neural activity patterns leading to reinforcement are also reentered more frequently. Reinforcement relies on dopaminergic activity in the ventral tegmental area (VTA), and animals shape their behavior to receive dopaminergic stimulation. Seeking evidence for a neural law of effect, we found that mice learn to reenter more frequently motor cortical activity patterns that trigger optogenetic VTA self-stimulation. Learning was accompanied by gradual shaping of these patterns, with participating neurons progressively increasing and aligning their covariance to that of the target pattern. Motor cortex patterns that lead to phasic dopaminergic VTA activity are progressively reinforced and shaped, suggesting a mechanism by which animals select and shape actions to reliably achieve reinforcement. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Implantable optoelectronic probes for in vivo optogenetics

NASA Astrophysics Data System (ADS)

Iseri, Ege; Kuzum, Duygu

2017-06-01

More than a decade has passed since optics and genetics came together and lead to the emerging technologies of optogenetics. The advent of light-sensitive opsins made it possible to optically trigger the neurons into activation or inhibition by using visible light. The importance of spatiotemporally isolating a segment of a neural network and controlling nervous signaling in a precise manner has driven neuroscience researchers and engineers to invest great efforts in designing high precision in vivo implantable devices. These efforts have focused on delivery of sufficient power to deep brain regions, while monitoring neural activity with high resolution and fidelity. In this review, we report the progress made in the field of hybrid optoelectronic neural interfaces that combine optical stimulation with electrophysiological recordings. Different approaches that incorporate optical or electrical components on implantable devices are discussed in detail. Advantages of various different designs as well as practical and fundamental limitations are summarized to illuminate the future of neurotechnology development.

Disentangling the attention network test: behavioral, event related potentials, and neural source analyses

PubMed Central

Galvao-Carmona, Alejandro; González-Rosa, Javier J.; Hidalgo-Muñoz, Antonio R.; Páramo, Dolores; Benítez, María L.; Izquierdo, Guillermo; Vázquez-Marrufo, Manuel

2014-01-01

Background: The study of the attentional system remains a challenge for current neuroscience. The “Attention Network Test” (ANT) was designed to study simultaneously three different attentional networks (alerting, orienting, and executive) based in subtraction of different experimental conditions. However, some studies recommend caution with these calculations due to the interactions between the attentional networks. In particular, it is highly relevant that several interpretations about attentional impairment have arisen from these calculations in diverse pathologies. Event related potentials (ERPs) and neural source analysis can be applied to disentangle the relationships between these attentional networks not specifically shown by behavioral measures. Results: This study shows that there is a basic level of alerting (tonic alerting) in the no cue (NC) condition, represented by a slow negative trend in the ERP trace prior to the onset of the target stimuli. A progressive increase in the CNV amplitude related to the amount of information provided by the cue conditions is also shown. Neural source analysis reveals specific modulations of the CNV related to a task-related expectancy presented in the NC condition; a late modulation triggered by the central cue (CC) condition and probably representing a generic motor preparation; and an early and late modulation for spatial cue (SC) condition suggesting specific motor and sensory preactivation. Finally, the first component in the information processing of the target stimuli modulated by the interaction between orienting network and the executive system can be represented by N1. Conclusions: The ANT is useful as a paradigm to study specific attentional mechanisms and their interactions. However, calculation of network effects is based in subtractions with non-comparable experimental conditions, as evidenced by the present data, which can induce misinterpretations in the study of the attentional capacity in human subjects. PMID:25352800

A High-Content Small Molecule Screen Identifies Sensitivity of Glioblastoma Stem Cells to Inhibition of Polo-Like Kinase 1

PubMed Central

Danovi, Davide; Folarin, Amos; Gogolok, Sabine; Ender, Christine; Elbatsh, Ahmed M. O.; Engström, Pär G.; Stricker, Stefan H.; Gagrica, Sladjana; Georgian, Ana; Yu, Ding; U, Kin Pong; Harvey, Kevin J.; Ferretti, Patrizia; Paddison, Patrick J.; Preston, Jane E.; Abbott, N. Joan; Bertone, Paul; Smith, Austin; Pollard, Steven M.

2013-01-01

Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF−/−, or p53−/−), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value. PMID:24204733

TrpM8-mediated somatosensation in mouse neocortex.

PubMed

Beukema, Patrick; Cecil, Katherine L; Peterson, Elena; Mann, Victor R; Matsushita, Megumi; Takashima, Yoshio; Navlakha, Saket; Barth, Alison L

2018-06-15

Somatosensation is a complex sense mediated by more than a dozen distinct neural subtypes in the periphery. Although pressure and touch sensation have been mapped to primary somatosensory cortex in rodents, it has been controversial whether pain and temperature inputs are also directed to this area. Here we use a well-defined somatosensory modality, cool sensation mediated by peripheral TrpM8-receptors, to investigate the neural substrate for cool perception in the mouse neocortex. Using activation of cutaneous TrpM8 receptor-expressing neurons, we identify candidate neocortical areas responsive for cool sensation. Initially, we optimized TrpM8 stimulation and determined that menthol, a selective TrpM8 agonist, was more effective than cool stimulation at inducing expression of the immediate-early gene c-fos in the spinal cord. We developed a broad-scale brain survey method for identification of activated brain areas, using automated methods to quantify c-fos immunoreactivity (fos-IR) across animals. Brain areas corresponding to the posterior insular cortex and secondary somatosensory (S2) show elevated fos-IR after menthol stimulation, in contrast to weaker activation in primary somatosensory cortex (S1). In addition, menthol exposure triggered fos-IR in piriform cortex, the amygdala, and the hypothalamus. Menthol-mediated activation was absent in TrpM8-knock-out animals. Our results indicate that cool somatosensory input broadly drives neural activity across the mouse brain, with neocortical signal most elevated in the posterior insula, as well as S2 and S1. These findings are consistent with data from humans indicating that the posterior insula is specialized for somatosensory information encoding temperature, pain, and gentle touch. © 2018 Wiley Periodicals, Inc.

Iniencephaly

MedlinePlus

... other neural tube defects. Information from the National Library of Medicine’s MedlinePlus Neural Tube Defects ... by improper closure of the neural tube (the part of a human embryo that becomes the brain and spinal cord) during fetal development. Iniencephaly is in the same family of neural ...

Cell reprogramming by 3D bioprinting of human fibroblasts in polyurethane hydrogel for fabrication of neural-like constructs.

PubMed

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 reprogrammed into neural crest-like stem cells by 3D bioprinting with the gel, and the reprogrammed cells underwent neural differentiation in the printed structure after induction. The neural-like tissue engineering constructs fabricated by 3D bioprinting from human fibroblasts may be applied for neuroregeneration or further developed as mini-brain for basic research and drug screening. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hypothalamic Dysfunction of the Thrombospondin Receptor α2δ-1 Underlies the Overeating and Obesity Triggered by Brain-Derived Neurotrophic Factor Deficiency

PubMed Central

Cordeira, Joshua W.; Felsted, Jennifer A.; Teillon, Sarah; Daftary, Shabrine; Panessiti, Micaella; Wirth, Jena; Sena-Esteves, Miguel

2014-01-01

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are critical components of the neural circuitry controlling appetite and body weight. Diminished BDNF signaling in mice results in severe hyperphagia and obesity. In humans, BDNF haploinsufficiency and the functional Bdnf Val66Met polymorphism have been linked to elevated food intake and body weight. The mechanisms underlying this dysfunction are poorly defined. We demonstrate a chief role of α2δ-1, a calcium channel subunit and thrombospondin receptor, in triggering overeating in mice with central BDNF depletion. We show reduced α2δ-1 cell-surface expression in the BDNF mutant ventromedial hypothalamus (VMH), an energy balance-regulating center. This deficit contributes to the hyperphagia exhibited by BDNF mutant mice because selective inhibition of α2δ-1 by gabapentin infusion into wild-type VMH significantly increases feeding and body weight gain. Importantly, viral-mediated α2δ-1 rescue in BDNF mutant VMH significantly mitigates their hyperphagia, obesity, and liver steatosis and normalizes deficits in glucose homeostasis. Whole-cell recordings in BDNF mutant VMH neurons revealed normal calcium currents but reduced frequency of EPSCs. These results suggest calcium channel-independent effects of α2δ-1 on feeding and implicate α2δ-1–thrombospondin interactions known to facilitate excitatory synapse assembly. Our findings identify a central mechanism mediating the inhibitory effects of BDNF on feeding. They also demonstrate a novel and critical role for α2δ-1 in appetite control and suggest a mechanism underlying weight gain in humans treated with gabapentinoid drugs. PMID:24403154

Self-organized dynamical complexity in human wakefulness and sleep: different critical brain-activity feedback for conscious and unconscious states.

PubMed

Allegrini, Paolo; Paradisi, Paolo; Menicucci, Danilo; Laurino, Marco; Piarulli, Andrea; Gemignani, Angelo

2015-09-01

Criticality reportedly describes brain dynamics. The main critical feature is the presence of scale-free neural avalanches, whose auto-organization is determined by a critical branching ratio of neural-excitation spreading. Other features, directly associated to second-order phase transitions, are: (i) scale-free-network topology of functional connectivity, stemming from suprathreshold pairwise correlations, superimposable, in waking brain activity, with that of ferromagnets at Curie temperature; (ii) temporal long-range memory associated to renewal intermittency driven by abrupt fluctuations in the order parameters, detectable in human brain via spatially distributed phase or amplitude changes in EEG activity. Herein we study intermittent events, extracted from 29 night EEG recordings, including presleep wakefulness and all phases of sleep, where different levels of mentation and consciousness are present. We show that while critical avalanching is unchanged, at least qualitatively, intermittency and functional connectivity, present during conscious phases (wakefulness and REM sleep), break down during both shallow and deep non-REM sleep. We provide a theory for fragmentation-induced intermittency breakdown and suggest that the main difference between conscious and unconscious states resides in the backwards causation, namely on the constraints that the emerging properties at large scale induce to the lower scales. In particular, while in conscious states this backwards causation induces a critical slowing down, preserving spatiotemporal correlations, in dreamless sleep we see a self-organized maintenance of moduli working in parallel. Critical avalanches are still present, and establish transient auto-organization, whose enhanced fluctuations are able to trigger sleep-protecting mechanisms that reinstate parallel activity. The plausible role of critical avalanches in dreamless sleep is to provide a rapid recovery of consciousness, if stimuli are highly arousing.

Self-organized dynamical complexity in human wakefulness and sleep: Different critical brain-activity feedback for conscious and unconscious states

NASA Astrophysics Data System (ADS)

Allegrini, Paolo; Paradisi, Paolo; Menicucci, Danilo; Laurino, Marco; Piarulli, Andrea; Gemignani, Angelo

2015-09-01

Criticality reportedly describes brain dynamics. The main critical feature is the presence of scale-free neural avalanches, whose auto-organization is determined by a critical branching ratio of neural-excitation spreading. Other features, directly associated to second-order phase transitions, are: (i) scale-free-network topology of functional connectivity, stemming from suprathreshold pairwise correlations, superimposable, in waking brain activity, with that of ferromagnets at Curie temperature; (ii) temporal long-range memory associated to renewal intermittency driven by abrupt fluctuations in the order parameters, detectable in human brain via spatially distributed phase or amplitude changes in EEG activity. Herein we study intermittent events, extracted from 29 night EEG recordings, including presleep wakefulness and all phases of sleep, where different levels of mentation and consciousness are present. We show that while critical avalanching is unchanged, at least qualitatively, intermittency and functional connectivity, present during conscious phases (wakefulness and REM sleep), break down during both shallow and deep non-REM sleep. We provide a theory for fragmentation-induced intermittency breakdown and suggest that the main difference between conscious and unconscious states resides in the backwards causation, namely on the constraints that the emerging properties at large scale induce to the lower scales. In particular, while in conscious states this backwards causation induces a critical slowing down, preserving spatiotemporal correlations, in dreamless sleep we see a self-organized maintenance of moduli working in parallel. Critical avalanches are still present, and establish transient auto-organization, whose enhanced fluctuations are able to trigger sleep-protecting mechanisms that reinstate parallel activity. The plausible role of critical avalanches in dreamless sleep is to provide a rapid recovery of consciousness, if stimuli are highly arousing.

Using human brain activity to guide machine learning.

PubMed

Fong, Ruth C; Scheirer, Walter J; Cox, David D

2018-03-29

Machine learning is a field of computer science that builds algorithms that learn. In many cases, machine learning algorithms are used to recreate a human ability like adding a caption to a photo, driving a car, or playing a game. While the human brain has long served as a source of inspiration for machine learning, little effort has been made to directly use data collected from working brains as a guide for machine learning algorithms. Here we demonstrate a new paradigm of "neurally-weighted" machine learning, which takes fMRI measurements of human brain activity from subjects viewing images, and infuses these data into the training process of an object recognition learning algorithm to make it more consistent with the human brain. After training, these neurally-weighted classifiers are able to classify images without requiring any additional neural data. We show that our neural-weighting approach can lead to large performance gains when used with traditional machine vision features, as well as to significant improvements with already high-performing convolutional neural network features. The effectiveness of this approach points to a path forward for a new class of hybrid machine learning algorithms which take both inspiration and direct constraints from neuronal data.

A scale out approach towards neural induction of human induced pluripotent stem cells for neurodevelopmental toxicity studies.

PubMed

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.

The role of the insula in intuitive expert bug detection in computer code: an fMRI study.

PubMed

Castelhano, Joao; Duarte, Isabel C; Ferreira, Carlos; Duraes, Joao; Madeira, Henrique; Castelo-Branco, Miguel

2018-05-09

Software programming is a complex and relatively recent human activity, involving the integration of mathematical, recursive thinking and language processing. The neural correlates of this recent human activity are still poorly understood. Error monitoring during this type of task, requiring the integration of language, logical symbol manipulation and other mathematical skills, is particularly challenging. We therefore aimed to investigate the neural correlates of decision-making during source code understanding and mental manipulation in professional participants with high expertise. The present fMRI study directly addressed error monitoring during source code comprehension, expert bug detection and decision-making. We used C code, which triggers the same sort of processing irrespective of the native language of the programmer. We discovered a distinct role for the insula in bug monitoring and detection and a novel connectivity pattern that goes beyond the expected activation pattern evoked by source code understanding in semantic language and mathematical processing regions. Importantly, insula activity levels were critically related to the quality of error detection, involving intuition, as signalled by reported initial bug suspicion, prior to final decision and bug detection. Activity in this salience network (SN) region evoked by bug suspicion was predictive of bug detection precision, suggesting that it encodes the quality of the behavioral evidence. Connectivity analysis provided evidence for top-down circuit "reutilization" stemming from anterior cingulate cortex (BA32), a core region in the SN that evolved for complex error monitoring such as required for this type of recent human activity. Cingulate (BA32) and anterolateral (BA10) frontal regions causally modulated decision processes in the insula, which in turn was related to activity of math processing regions in early parietal cortex. In other words, earlier brain regions used during evolution for other functions seem to be reutilized in a top-down manner for a new complex function, in an analogous manner as described for other cultural creations such as reading and literacy.

Development of the posterior neural tube in human embryos.

PubMed

Saitsu, Hirotomo; Yamada, Shigehito; Uwabe, Chigako; Ishibashi, Makoto; Shiota, Kohei

2004-12-01

Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Because normal development of the PNT is not fully understood, pathogenesis of spinal neural tube defects remains elusive. To clarify the mechanism of PNT development, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the developing PNT can be divided into three parts: 1) the most rostral region, which corresponds to the posterior part of the primary neural tube, 2) the junctional region of the primary and secondary neural tubes, and 3) the caudal region, which emerges from the neural cord. In the junctional region, the axially-condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord at the stage of posterior neuropore closure, while the notochord was directly attached to the neural plate/tube in the most rostral region. A single cavity was found to be formed in the AM as the presumptive luminal surface cells were radially aligned in the junctional region prior to the formation of the neural cord. The single cavity was continuous with the central cavity of the primary neural tube. In contrast, multiple or isolated cavities were frequently observed in the caudal region of the PNT. Our observation suggests that the junctional region of the PNT is distinct from other regions in terms of the relationship with the notochord and the mode of cavitation during secondary neurulation.

Human mesostriatal response tracks motivational tendencies under naturalistic goal conflict

PubMed Central

Gonen, Tal; Soreq, Eyal; Eldar, Eran; Ben-Simon, Eti; Raz, Gal

2016-01-01

Goal conflict situations, involving the simultaneous presence of reward and punishment, occur commonly in real life, and reflect well-known individual differences in the behavioral tendency to approach or avoid. However, despite accumulating neural depiction of motivational processing, the investigation of naturalistic approach behavior and its interplay with individual tendencies is remarkably lacking. We developed a novel ecological interactive scenario which triggers motivational behavior under high or low goal conflict conditions. Fifty-five healthy subjects played the game during a functional magnetic resonance imaging scan. A machine-learning approach was applied to classify approach/avoidance behaviors during the game. To achieve an independent measure of individual tendencies, an integrative profile was composed from three established theoretical models. Results demonstrated that approach under high relative to low conflict involved increased activity in the ventral tegmental area (VTA), peri-aquaductal gray, ventral striatum (VS) and precuneus. Notably, only VS and VTA activations during high conflict discriminated between approach/avoidance personality profiles, suggesting that the relationship between individual personality and naturalistic motivational tendencies is uniquely associated with the mesostriatal pathway. VTA–VS further demonstrated stronger coupling during high vs low conflict. These findings are the first to unravel the multilevel relationship among personality profile, approach tendencies in naturalistic set-up and their underlying neural manifestation, thus enabling new avenues for investigating approach-related psychopathologies. PMID:26833917

How task demands shape brain responses to visual food cues.

PubMed

Pohl, Tanja Maria; Tempelmann, Claus; Noesselt, Toemme

2017-06-01

Several previous imaging studies have aimed at identifying the neural basis of visual food cue processing in humans. However, there is little consistency of the functional magnetic resonance imaging (fMRI) results across studies. Here, we tested the hypothesis that this variability across studies might - at least in part - be caused by the different tasks employed. In particular, we assessed directly the influence of task set on brain responses to food stimuli with fMRI using two tasks (colour vs. edibility judgement, between-subjects design). When participants judged colour, the left insula, the left inferior parietal lobule, occipital areas, the left orbitofrontal cortex and other frontal areas expressed enhanced fMRI responses to food relative to non-food pictures. However, when judging edibility, enhanced fMRI responses to food pictures were observed in the superior and middle frontal gyrus and in medial frontal areas including the pregenual anterior cingulate cortex and ventromedial prefrontal cortex. This pattern of results indicates that task sets can significantly alter the neural underpinnings of food cue processing. We propose that judging low-level visual stimulus characteristics - such as colour - triggers stimulus-related representations in the visual and even in gustatory cortex (insula), whereas discriminating abstract stimulus categories activates higher order representations in both the anterior cingulate and prefrontal cortex. Hum Brain Mapp 38:2897-2912, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Long-range traveling waves of activity triggered by local dichoptic stimulation in V1 of behaving monkeys

PubMed Central

Yang, Zhiyong; Heeger, David J.; Blake, Randolph

2014-01-01

Traveling waves of cortical activity, in which local stimulation triggers lateral spread of activity to distal locations, have been hypothesized to play an important role in cortical function. However, there is conflicting physiological evidence for the existence of spreading traveling waves of neural activity triggered locally. Dichoptic stimulation, in which the two eyes view dissimilar monocular patterns, can lead to dynamic wave-like fluctuations in visual perception and therefore, provides a promising means for identifying and studying cortical traveling waves. Here, we used voltage-sensitive dye imaging to test for the existence of traveling waves of activity in the primary visual cortex of awake, fixating monkeys viewing dichoptic stimuli. We find clear traveling waves that are initiated by brief, localized contrast increments in one of the monocular patterns and then, propagate at speeds of ∼30 mm/s. These results demonstrate that under an appropriate visual context, circuitry in visual cortex in alert animals is capable of supporting long-range traveling waves triggered by local stimulation. PMID:25343785

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

PubMed

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.

Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manceur, Aziza P.; Donnelly Centre, University of Toronto, Toronto, Ontario; Tseng, Michael

2011-09-10

The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B)more » inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.« less

Involvement of the human midbrain and thalamus in auditory deviance detection.

PubMed

Cacciaglia, Raffaele; Escera, Carles; Slabu, Lavinia; Grimm, Sabine; Sanjuán, Ana; Ventura-Campos, Noelia; Ávila, César

2015-02-01

Prompt detection of unexpected changes in the sensory environment is critical for survival. In the auditory domain, the occurrence of a rare stimulus triggers a cascade of neurophysiological events spanning over multiple time-scales. Besides the role of the mismatch negativity (MMN), whose cortical generators are located in supratemporal areas, cumulative evidence suggests that violations of auditory regularities can be detected earlier and lower in the auditory hierarchy. Recent human scalp recordings have shown signatures of auditory mismatch responses at shorter latencies than those of the MMN. Moreover, animal single-unit recordings have demonstrated that rare stimulus changes cause a release from stimulus-specific adaptation in neurons of the primary auditory cortex, the medial geniculate body (MGB), and the inferior colliculus (IC). Although these data suggest that change detection is a pervasive property of the auditory system which may reside upstream cortical sites, direct evidence for the involvement of subcortical stages in the human auditory novelty system is lacking. Using event-related functional magnetic resonance imaging during a frequency oddball paradigm, we here report that auditory deviance detection occurs in the MGB and the IC of healthy human participants. By implementing a random condition controlling for neural refractoriness effects, we show that auditory change detection in these subcortical stations involves the encoding of statistical regularities from the acoustic input. These results provide the first direct evidence of the existence of multiple mismatch detectors nested at different levels along the human ascending auditory pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

How Neural Networks Learn from Experience.

ERIC Educational Resources Information Center

Hinton, Geoffrey E.

1992-01-01

Discusses computational studies of learning in artificial neural networks and findings that may provide insights into the learning abilities of the human brain. Describes efforts to test theories about brain information processing, using artificial neural networks. Vignettes include information concerning how a neural network represents…

Uniform neural tissue models produced on synthetic hydrogels using standard culture techniques.

PubMed

Barry, Christopher; Schmitz, Matthew T; Propson, Nicholas E; Hou, Zhonggang; Zhang, Jue; Nguyen, Bao K; Bolin, Jennifer M; Jiang, Peng; McIntosh, Brian E; Probasco, Mitchell D; Swanson, Scott; Stewart, Ron; Thomson, James A; Schwartz, Michael P; Murphy, William L

2017-11-01

The aim of the present study was to test sample reproducibility for model neural tissues formed on synthetic hydrogels. Human embryonic stem (ES) cell-derived precursor cells were cultured on synthetic poly(ethylene glycol) (PEG) hydrogels to promote differentiation and self-organization into model neural tissue constructs. Neural progenitor, vascular, and microglial precursor cells were combined on PEG hydrogels to mimic developmental timing, which produced multicomponent neural constructs with 3D neuronal and glial organization, organized vascular networks, and microglia with ramified morphologies. Spearman's rank correlation analysis of global gene expression profiles and a comparison of coefficient of variation for expressed genes demonstrated that replicate neural constructs were highly uniform to at least day 21 for samples from independent experiments. We also demonstrate that model neural tissues formed on PEG hydrogels using a simplified neural differentiation protocol correlated more strongly to in vivo brain development than samples cultured on tissue culture polystyrene surfaces alone. These results provide a proof-of-concept demonstration that 3D cellular models that mimic aspects of human brain development can be produced from human pluripotent stem cells with high sample uniformity between experiments by using standard culture techniques, cryopreserved cell stocks, and a synthetic extracellular matrix. Impact statement Pluripotent stem (PS) cells have been characterized by an inherent ability to self-organize into 3D "organoids" resembling stomach, intestine, liver, kidney, and brain tissues, offering a potentially powerful tool for modeling human development and disease. However, organoid formation must be quantitatively reproducible for applications such as drug and toxicity screening. Here, we report a strategy to produce uniform neural tissue constructs with reproducible global gene expression profiles for replicate samples from multiple experiments.

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

PubMed

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.

Closed-Loop Estimation of Retinal Network Sensitivity by Local Empirical Linearization

PubMed Central

2018-01-01

Abstract Understanding how sensory systems process information depends crucially on identifying which features of the stimulus drive the response of sensory neurons, and which ones leave their response invariant. This task is made difficult by the many nonlinearities that shape sensory processing. Here, we present a novel perturbative approach to understand information processing by sensory neurons, where we linearize their collective response locally in stimulus space. We added small perturbations to reference stimuli and tested if they triggered visible changes in the responses, adapting their amplitude according to the previous responses with closed-loop experiments. We developed a local linear model that accurately predicts the sensitivity of the neural responses to these perturbations. Applying this approach to the rat retina, we estimated the optimal performance of a neural decoder and showed that the nonlinear sensitivity of the retina is consistent with an efficient encoding of stimulus information. Our approach can be used to characterize experimentally the sensitivity of neural systems to external stimuli locally, quantify experimentally the capacity of neural networks to encode sensory information, and relate their activity to behavior. PMID:29379871

Carbon nanotube multilayered nanocomposites as multifunctional substrates for actuating neuronal differentiation and functions of neural stem cells.

PubMed

Shao, Han; Li, Tingting; Zhu, Rong; Xu, Xiaoting; Yu, Jiandong; Chen, Shengfeng; Song, Li; Ramakrishna, Seeram; Lei, Zhigang; Ruan, Yiwen; He, Liumin

2018-08-01

Carbon nanotubes (CNTs) have shown potential applications in neuroscience as growth substrates owing to their numerous unique properties. However, a key concern in the fabrication of homogeneous composites is the serious aggregation of CNTs during incorporation into the biomaterial matrix. Moreover, the regulation mechanism of CNT-based substrates on neural differentiation remains unclear. Here, a novel strategy was introduced for the construction of CNT nanocomposites via layer-by-layer assembly of negatively charged multi-walled CNTs and positively charged poly(dimethyldiallylammonium chloride). Results demonstrated that the CNT-multilayered nanocomposites provided a potent regulatory signal over neural stem cells (NSCs), including cell adhesion, viability, differentiation, neurite outgrowth, and electrophysiological maturation of NSC-derived neurons. Importantly, the dynamic molecular mechanisms in the NSC differentiation involved the integrin-mediated interactions between NSCs and CNT multilayers, thereby activating focal adhesion kinase, subsequently triggering downstream signaling events to regulate neuronal differentiation and synapse formation. This study provided insights for future applications of CNT-multilayered nanomaterials in neural fields as potent modulators of stem cell behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multisensory Control of Stabilization Reflexes

DTIC Science & Technology

2012-08-22

Dr Simon Schultz (Neural Coding), Dr Manos Drakakis (Low-power VLSI technology), and Dr Reiko Tanaka (Compound Control). To study the functional...Krapp H.G., and Schultz S.R.: Spike-triggered independent component analysis: application to a fly motion-sensitive neuron. Visual Neuroscience, 8...Tanaka, RI.: Characterization of insect gaze control systems. 18th World Congress of International Federation of Automated Control (IFAC), Milan

European Seminar on Neural Computing

DTIC Science & Technology

1988-08-31

elements can be fabricated on a single chip . Two specific oriented language (for example, SMALLTALK or cellular arrays, namely, the programmable systolic... chip POOL) the basic concepts are: objects are viewed as (Fisher, 1983) and the connection machine (Treleaven, active, they may contain state, and...flow computer the availability of 1. Programmable Systolic Chip . Programmable Sys- input operands triggers the execution of the instruction tolic Chips

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

PubMed

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

2017-06-01

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 ~100ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250ms 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. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Generation of the Human Biped Stance by a Neural Controller Able to Compensate Neurological Time Delay

PubMed Central

Jiang, Ping; Chiba, Ryosuke; Takakusaki, Kaoru; Ota, Jun

2016-01-01

The development of a physiologically plausible computational model of a neural controller that can realize a human-like biped stance is important for a large number of potential applications, such as assisting device development and designing robotic control systems. In this paper, we develop a computational model of a neural controller that can maintain a musculoskeletal model in a standing position, while incorporating a 120-ms neurological time delay. Unlike previous studies that have used an inverted pendulum model, a musculoskeletal model with seven joints and 70 muscular-tendon actuators is adopted to represent the human anatomy. Our proposed neural controller is composed of both feed-forward and feedback controls. The feed-forward control corresponds to the constant activation input necessary for the musculoskeletal model to maintain a standing posture. This compensates for gravity and regulates stiffness. The developed neural controller model can replicate two salient features of the human biped stance: (1) physiologically plausible muscle activations for quiet standing; and (2) selection of a low active stiffness for low energy consumption. PMID:27655271

Silicon nanodisk array with a fin field-effect transistor for time-domain weighted sum calculation toward massively parallel spiking neural networks

NASA Astrophysics Data System (ADS)

Tohara, Takashi; Liang, Haichao; Tanaka, Hirofumi; Igarashi, Makoto; Samukawa, Seiji; Endo, Kazuhiko; Takahashi, Yasuo; Morie, Takashi

2016-03-01

A nanodisk array connected with a fin field-effect transistor is fabricated and analyzed for spiking neural network applications. This nanodevice performs weighted sums in the time domain using rising slopes of responses triggered by input spike pulses. The nanodisk arrays, which act as a resistance of several giga-ohms, are fabricated using a self-assembly bio-nano-template technique. Weighted sums are achieved with an energy dissipation on the order of 1 fJ, where the number of inputs can be more than one hundred. This amount of energy is several orders of magnitude lower than that of conventional digital processors.

Oxytocin promotes social bonding in dogs.

PubMed

Romero, Teresa; Nagasawa, Miho; Mogi, Kazutaka; Hasegawa, Toshikazu; Kikusui, Takefumi

2014-06-24

Recent evidence suggests that enduring social bonds have fitness benefits. However, very little is known about the neural circuitry and neurochemistry underlying the formation and maintenance of stable social bonds outside reproductive contexts. Oxytocin (OT), a neuropeptide synthetized by the hypothalamus in mammals, regulates many complex forms of social behavior and cognition in both human and nonhuman animals. Animal research, however, has concentrated on monogamous mammals, and it remains unknown whether OT also modulates social bonds in nonreproductive contexts. In this study we provide behavioral evidence that exogenous OT promotes positive social behaviors in the domestic dog toward not only conspecifics but also human partners. Specifically, when sprayed with OT, dogs showed higher social orientation and affiliation toward their owners and higher affiliation and approach behaviors toward dog partners than when sprayed with placebo. Additionally, the exchange of socio-positive behaviors with dog partners triggered the release of endogenous OT, highlighting the involvement of OT in the development of social relationships in the domestic dog. These data provide new insight into the mechanisms that facilitate the maintenance of close social bonds beyond immediate reproductive interest or genetic ties and complement a growing body of evidence that identifies OT as one of the neurochemical foundations of sociality in mammalian species.

Human high intelligence is involved in spectral redshift of biophotonic activities in the brain

PubMed Central

Wang, Niting; Li, Zehua; Xiao, Fangyan; Dai, Jiapei

2016-01-01

Human beings hold higher intelligence than other animals on Earth; however, it is still unclear which brain properties might explain the underlying mechanisms. The brain is a major energy-consuming organ compared with other organs. Neural signal communications and information processing in neural circuits play an important role in the realization of various neural functions, whereas improvement in cognitive function is driven by the need for more effective communication that requires less energy. Combining the ultraweak biophoton imaging system (UBIS) with the biophoton spectral analysis device (BSAD), we found that glutamate-induced biophotonic activities and transmission in the brain, which has recently been demonstrated as a novel neural signal communication mechanism, present a spectral redshift from animals (in order of bullfrog, mouse, chicken, pig, and monkey) to humans, even up to a near-infrared wavelength (∼865 nm) in the human brain. This brain property may be a key biophysical basis for explaining high intelligence in humans because biophoton spectral redshift could be a more economical and effective measure of biophotonic signal communications and information processing in the human brain. PMID:27432962

Development of a computational model on the neural activity patterns of a visual working memory in a hierarchical feedforward Network

NASA Astrophysics Data System (ADS)

An, Soyoung; Choi, Woochul; Paik, Se-Bum

2015-11-01

Understanding the mechanism of information processing in the human brain remains a unique challenge because the nonlinear interactions between the neurons in the network are extremely complex and because controlling every relevant parameter during an experiment is difficult. Therefore, a simulation using simplified computational models may be an effective approach. In the present study, we developed a general model of neural networks that can simulate nonlinear activity patterns in the hierarchical structure of a neural network system. To test our model, we first examined whether our simulation could match the previously-observed nonlinear features of neural activity patterns. Next, we performed a psychophysics experiment for a simple visual working memory task to evaluate whether the model could predict the performance of human subjects. Our studies show that the model is capable of reproducing the relationship between memory load and performance and may contribute, in part, to our understanding of how the structure of neural circuits can determine the nonlinear neural activity patterns in the human brain.

Detection of whale calls in noise: performance comparison between a beluga whale, human listeners, and a neural network.

PubMed

Erbe, C

2000-07-01

This article examines the masking by anthropogenic noise of beluga whale calls. Results from human masking experiments and a software backpropagation neural network are compared to the performance of a trained beluga whale. The goal was to find an accurate, reliable, and fast model to replace lengthy and expensive animal experiments. A beluga call was masked by three types of noise, an icebreaker's bubbler system and propeller noise, and ambient arctic ice-cracking noise. Both the human experiment and the neural network successfully modeled the beluga data in the sense that they classified the noises in the same order from strongest to weakest masking as the whale and with similar call-detection thresholds. The neural network slightly outperformed the humans. Both models were then used to predict the masking of a fourth type of noise, Gaussian white noise. Their prediction ability was judged by returning to the aquarium to measure masked-hearing thresholds of a beluga in white noise. Both models and the whale identified bubbler noise as the strongest masker, followed by ramming, then white noise. Natural ice-cracking noise masked the least. However, the humans and the neural network slightly overpredicted the amount of masking for white noise. This is neglecting individual variation in belugas, because only one animal could be trained. Comparing the human model to the neural network model, the latter has the advantage of objectivity, reproducibility of results, and efficiency, particularly if the interference of a large number of signals and noise is to be examined.

Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning

NASA Astrophysics Data System (ADS)

Xu, Tao; Xiao, Na; Zhai, Xiaolong; Chan, Pak Kwan; Tin, Chung

2018-02-01

Objective. Damage to the brain, as a result of various medical conditions, impacts the everyday life of patients and there is still no complete cure to neurological disorders. Neuroprostheses that can functionally replace the damaged neural circuit have recently emerged as a possible solution to these problems. Here we describe the development of a real-time cerebellar neuroprosthetic system to substitute neural function in cerebellar circuitry for learning delay eyeblink conditioning (DEC). Approach. The system was empowered by a biologically realistic spiking neural network (SNN) model of the cerebellar neural circuit, which considers the neuronal population and anatomical connectivity of the network. The model simulated synaptic plasticity critical for learning DEC. This SNN model was carefully implemented on a field programmable gate array (FPGA) platform for real-time simulation. This hardware system was interfaced in in vivo experiments with anesthetized rats and it used neural spikes recorded online from the animal to learn and trigger conditioned eyeblink in the animal during training. Main results. This rat-FPGA hybrid system was able to process neuronal spikes in real-time with an embedded cerebellum model of ~10 000 neurons and reproduce learning of DEC with different inter-stimulus intervals. Our results validated that the system performance is physiologically relevant at both the neural (firing pattern) and behavioral (eyeblink pattern) levels. Significance. This integrated system provides the sufficient computation power for mimicking the cerebellar circuit in real-time. The system interacts with the biological system naturally at the spike level and can be generalized for including other neural components (neuron types and plasticity) and neural functions for potential neuroprosthetic applications.

Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development

PubMed Central

Mora-Bermúdez, Felipe; Badsha, Farhath; Kanton, Sabina; Camp, J Gray; Vernot, Benjamin; Köhler, Kathrin; Voigt, Birger; Okita, Keisuke; Maricic, Tomislav; He, Zhisong; Lachmann, Robert; Pääbo, Svante; Treutlein, Barbara; Huttner, Wieland B

2016-01-01

Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistofluorescence, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution. DOI: http://dx.doi.org/10.7554/eLife.18683.001 PMID:27669147

Anticipating conflict facilitates controlled stimulus-response selection

PubMed Central

Correa, Ángel; Rao, Anling; Nobre, Anna C.

2014-01-01

Cognitive control can be triggered in reaction to previous conflict, as suggested by the finding of sequential effects in conflict tasks. Can control also be triggered proactively by presenting cues predicting conflict (‘proactive control’)? We exploited the high temporal resolution of event-related potentials (ERPs) and controlled for sequential effects to ask whether proactive control based on anticipating conflict modulates neural activity related to cognitive control, as may be predicted from the conflict-monitoring model. ERPs associated with conflict detection (N2) were measured during a cued flanker task. Symbolic cues were either informative or neutral with respect to whether the target involved conflicting or congruent responses. Sequential effects were controlled by analysing the congruency of the previous trial. The results showed that cuing conflict facilitated conflict resolution and reduced the N2 latency. Other potentials (frontal N1 and P3) were also modulated by cuing conflict. Cuing effects were most evident after congruent than after incongruent trials. This interaction between cuing and sequential effects suggests neural overlap between the control networks triggered by proactive and reactive signals. This finding clarifies why previous neuroimaging studies, in which reactive sequential effects were not controlled, have rarely found anticipatory effects upon conflict-related activity. Finally, the high temporal resolution of ERPs was critical to reveal a temporal modulation of conflict detection by proactive control. This novel finding suggests that anticipating conflict speeds up conflict detection and resolution. Recent research suggests that this anticipatory mechanism may be mediated by pre-activation of the ACC during the preparatory interval. PMID:18823248

Assessment of earthquake-triggered landslide susceptibility in El Salvador based on an Artificial Neural Network model

NASA Astrophysics Data System (ADS)

García-Rodríguez, M. J.; Malpica, J. A.

2010-06-01

This paper presents an approach for assessing earthquake-triggered landslide susceptibility using artificial neural networks (ANNs). The computational method used for the training process is a back-propagation learning algorithm. It is applied to El Salvador, one of the most seismically active regions in Central America, where the last severe destructive earthquakes occurred on 13 January 2001 (Mw 7.7) and 13 February 2001 (Mw 6.6). The first one triggered more than 600 landslides (including the most tragic, Las Colinas landslide) and killed at least 844 people. The ANN is designed and programmed to develop landslide susceptibility analysis techniques at a regional scale. This approach uses an inventory of landslides and different parameters of slope instability: slope gradient, elevation, aspect, mean annual precipitation, lithology, land use, and terrain roughness. The information obtained from ANN is then used by a Geographic Information System (GIS) to map the landslide susceptibility. In a previous work, a Logistic Regression (LR) was analysed with the same parameters considered in the ANN as independent variables and the occurrence or non-occurrence of landslides as dependent variables. As a result, the logistic approach determined the importance of terrain roughness and soil type as key factors within the model. The results of the landslide susceptibility analysis with ANN are checked using landslide location data. These results show a high concordance between the landslide inventory and the high susceptibility estimated zone. Finally, a comparative analysis of the ANN and LR models are made. The advantages and disadvantages of both approaches are discussed using Receiver Operating Characteristic (ROC) curves.

Expansion and differentiation of neural progenitors derived from the human adult enteric nervous system.

PubMed

Metzger, Marco; Bareiss, Petra M; Danker, Timm; Wagner, Silvia; Hennenlotter, Joerg; Guenther, Elke; Obermayr, Florian; Stenzl, Arnulf; Koenigsrainer, Alfred; Skutella, Thomas; Just, Lothar

2009-12-01

Neural stem and progenitor cells from the enteric nervous system have been proposed for use in cell-based therapies against specific neurogastrointestinal disorders. Recently, enteric neural progenitors were generated from human neonatal and early postnatal (until 5 years after birth) gastrointestinal tract tissues. We investigated the proliferation and differentiation of enteric nervous system progenitors isolated from human adult gastrointestinal tract. Human enteric spheroids were generated from adult small and large intestine tissues and then expanded and differentiated, depending on the applied cell culture conditions. For implantation studies, spheres were grafted into fetal slice cultures and embryonic aganglionic hindgut explants from mice. Differentiating enteric neural progenitors were characterized by 5-bromo-2-deoxyuridine labeling, in situ hybridization, immunocytochemistry, quantitative real-time polymerase chain reaction, and electrophysiological studies. The yield of human neurosphere-like bodies was increased by culture in conditional medium derived from fetal mouse enteric progenitors. We were able to generate proliferating enterospheres from adult human small or large intestine tissues; these enterospheres could be subcultured and maintained for several weeks in vitro. Spheroid-derived cells could be differentiated into a variety of neuronal subtypes and glial cells with characteristics of the enteric nervous system. Experiments involving implantation into organotypic intestinal cultures showed the differentiation capacity of neural progenitors in a 3-dimensional environment. It is feasible to isolate and expand enteric progenitor cells from human adult tissue. These findings offer new strategies for enteric stem cell research and future cell-based therapies.

Human brain networks function in connectome-specific harmonic waves.

PubMed

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.

Investigating the mechanism(s) underlying switching between states in bipolar disorder

PubMed Central

Young, Jared W.; Dulcis, Davide

2015-01-01

Bipolar Disorder (BD) is a unique disorder that transcends domains of function since the same patient can exhibit depression or mania, states with polar opposite mood symptoms. During depression, people feel helplessness, reduced energy, and risk aversion, while with mania behaviors include grandiosity, increased energy, less sleep, and risk preference. The neural mechanism(s) underlying each state are gaining clarity, with catecholaminergic disruption seen during mania, and cholinergic dysfunction during depression. The fact that the same patient cycles/switches between these states is the defining characteristic of BD however. Of greater importance therefore, is the mechanism(s) underlying cycling from one state - and its associated neural changes - to another, considered the ‘holy grail’ of BD research. Herein, we review studies investigating triggers that induce switching to these states. By identifying such triggers, researchers can study neural mechanisms underlying each state and importantly how such mechanistic changes can occur in the same subject. Current animal models of this switch are also discussed, from submissive- and dominant-behaviors to kindling effects. Focus however, is placed on how seasonal changes can induce manic and depressive states in BD sufferers. Importantly, changing photoperiod lengths can induce local switches in neurotransmitter expression in normal animals, from increased catecholaminergic expression during periods of high activity, to increased somatostatin and corticotrophin releasing factor during periods of low activity. Identifying susceptibilities to this switch would enable the development of targeted animal models. From animal models, targeted treatments could be developed and tested that would minimize the likelihood of switching. PMID:25814263

Human Neural Cell-Based Biosensor

DTIC Science & Technology

2013-05-28

ionotropic receptors in human embryonic stem cell derived neural progenitors. Neuroscience. 2011 Sep 29;192:793-805. Krishnamoorthy M, Gerwe BA, Scharer...coupled receptors . Pharmacol Ther. 2011 Mar;129(3):290-306. Workshop/conference abstracts, presentations, posters, and papers Powe, A, et al

L-Dopa decarboxylase expression profile in human cancer cells.

PubMed

Chalatsa, Ioanna; Nikolouzou, Eleftheria; Fragoulis, Emmanuel G; Vassilacopoulou, Dido

2011-02-01

L-Dopa decarboxylase (DDC) catalyses the decarboxylation of L-Dopa. It has been shown that the DDC gene undergoes alternative splicing within its 5'-untranslated region (UTR), in a tissue-specific manner, generating identical protein products. The employment of two alternative 5'UTRs is thought to be responsible for tissue-specific expression of the human DDC mRNA. In this study, we focused on the investigation of the nature of the mRNA expression in human cell lines of neural and non-neural origin. Our results show the expression of a neural-type DDC mRNA splice variant, lacking exon 3 in all cell lines studied. Co-expression of the full length non-neural DDC mRNA and the neural-type DDC splice variant lacking exon 3 was detected in all cell lines. The alternative DDC protein isoform, Alt-DDC, was detected in SH-SY5Y and HeLa cells. Our findings suggest that the human DDC gene undergoes complex processing, leading to the formation of multiple mRNA isoforms. The study of the significance of this phenomenon of multiple DDC mRNA isoforms could provide us with new information leading to the elucidation of the complex biological pathways that the human enzyme is involved in.

Dissociation between the neural correlates of conscious face perception and visual attention.

PubMed

Navajas, Joaquin; Nitka, Aleksander W; Quian Quiroga, Rodrigo

2017-08-01

Given the higher chance to recognize attended compared to unattended stimuli, the specific neural correlates of these two processes, attention and awareness, tend to be intermingled in experimental designs. In this study, we dissociated the neural correlates of conscious face perception from the effects of visual attention. To do this, we presented faces at the threshold of awareness and manipulated attention through the use of exogenous prestimulus cues. We show that the N170 component, a scalp EEG marker of face perception, was modulated independently by attention and by awareness. An earlier P1 component was not modulated by either of the two effects and a later P3 component was indicative of awareness but not of attention. These claims are supported by converging evidence from (a) modulations observed in the average evoked potentials, (b) correlations between neural and behavioral data at the single-subject level, and (c) single-trial analyses. Overall, our results show a clear dissociation between the neural substrates of attention and awareness. Based on these results, we argue that conscious face perception is triggered by a boost in face-selective cortical ensembles that can be modulated by, but are still independent from, visual attention. © 2017 Society for Psychophysiological Research.

Tympanal mechanics and neural responses in the ears of a noctuid moth

NASA Astrophysics Data System (ADS)

Ter Hofstede, Hannah M.; Goerlitz, Holger R.; Montealegre-Z, Fernando; Robert, Daniel; Holderied, Marc W.

2011-12-01

Ears evolved in many groups of moths to detect the echolocation calls of predatory bats. Although the neurophysiology of bat detection has been intensively studied in moths for decades, the relationship between sound-induced movement of the noctuid tympanic membrane and action potentials in the auditory sensory cells (A1 and A2) has received little attention. Using laser Doppler vibrometry, we measured the velocity and displacement of the tympanum in response to pure tone pulses for moths that were intact or prepared for neural recording. When recording from the auditory nerve, the displacement of the tympanum at the neural threshold remained constant across frequencies, whereas velocity varied with frequency. This suggests that the key biophysical parameter for triggering action potentials in the sensory cells of noctuid moths is tympanum displacement, not velocity. The validity of studies on the neurophysiology of moth hearing rests on the assumption that the dissection and recording procedures do not affect the biomechanics of the ear. There were no consistent differences in tympanal velocity or displacement when moths were intact or prepared for neural recordings for sound levels close to neural threshold, indicating that this and other neurophysiological studies provide good estimates of what intact moths hear at threshold.

Neurodegeneration and adaptation in response to low-dose photon irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Limoli, Charles L.

2014-10-27

Neural stem and precursor cells (i.e. multipotent neural cells) are concentrated in the neurogenic regions of the brain (hippocampal dentate gyrus, subventricular zones), and considerable evidence suggests that these cells are important in mediating the stress response of the CNS after damage from ionizing radiation. The capability of these cells to proliferate, migrate and differentiate (i.e. to undergo neurogenesis) suggests they can participate in the repair and maintenance of CNS functions by replacing brain cells damaged or depleted due to irradiation. Importantly, we have shown that multipotent neural cells are markedly sensitive to irradiation and oxidative stress, insults that compromisemore » neurogenesis and hasten the onset and progression of degenerative processes that are likely to have an adverse impact on cognition. Our past and current work has demonstrated that relatively low doses of radiation cause a persistent (weeks-months) oxidative stress in multipotent neural cells that can elicit a range of degenerative sequelae in the CNS. Therefore, our project is focused on determining the extent that endogenous and redox sensitive multipotent neural cells represent important radioresponsive targets for low dose radiation effects. We hypothesize that the activation of redox sensitive signaling can trigger radioadaptive changes in these cells that can be either harmful or beneficial to overall cognitive health.« less

SMAD7 directly converts human embryonic stem cells to telencephalic fate by a default mechanism

PubMed Central

Ozair, Mohammad Zeeshan; Noggle, Scott; Warmflash, Aryeh; Krzyspiak, Joanna Ela; Brivanlou, Ali H.

2013-01-01

Human embryonic stem cells (hESCs) provide a valuable window into the dissection of the molecular circuitry underlying the early formation of the human forebrain. However, dissection of signaling events in forebrain development using current protocols is complicated by non-neural contamination and fluctuation of extrinsic influences. Here we show that SMAD7, a cell-intrinsic inhibitor of TGFβ signaling, is sufficient to directly convert pluripotent hESCs to an anterior neural fate. Time-course gene expression revealed down-regulation of MAPK components, and combining MEK1/2 inhibition with SMAD7-mediated TGFβ inhibition promoted telencephalic conversion. FGF-MEK and TGFβ-SMAD signaling maintain hESCs by promoting pluripotency genes and repressing neural genes. Our findings suggest that in the absence of these cues, pluripotent cells simply revert to a program of neural conversion. Hence the “primed” state of hESCs requires inhibition of the “default” state of neural fate acquisition. This has parallels in amphibians, suggesting an evolutionarily conserved mechanism. PMID:23034881

Functional recordings from awake, behaving rodents through a microchannel based regenerative neural interface

NASA Astrophysics Data System (ADS)

Gore, Russell K.; Choi, Yoonsu; Bellamkonda, Ravi; English, Arthur

2015-02-01

Objective. Neural interface technologies could provide controlling connections between the nervous system and external technologies, such as limb prosthetics. The recording of efferent, motor potentials is a critical requirement for a peripheral neural interface, as these signals represent the user-generated neural output intended to drive external devices. Our objective was to evaluate structural and functional neural regeneration through a microchannel neural interface and to characterize potentials recorded from electrodes placed within the microchannels in awake and behaving animals. Approach. Female rats were implanted with muscle EMG electrodes and, following unilateral sciatic nerve transection, the cut nerve was repaired either across a microchannel neural interface or with end-to-end surgical repair. During a 13 week recovery period, direct muscle responses to nerve stimulation proximal to the transection were monitored weekly. In two rats repaired with the neural interface, four wire electrodes were embedded in the microchannels and recordings were obtained within microchannels during proximal stimulation experiments and treadmill locomotion. Main results. In these proof-of-principle experiments, we found that axons from cut nerves were capable of functional reinnervation of distal muscle targets, whether regenerating through a microchannel device or after direct end-to-end repair. Discrete stimulation-evoked and volitional potentials were recorded within interface microchannels in a small group of awake and behaving animals and their firing patterns correlated directly with intramuscular recordings during locomotion. Of 38 potentials extracted, 19 were identified as motor axons reinnervating tibialis anterior or soleus muscles using spike triggered averaging. Significance. These results are evidence for motor axon regeneration through microchannels and are the first report of in vivo recordings from regenerated motor axons within microchannels in a small group of awake and behaving animals. These unique findings provide preliminary evidence that efferent, volitional motor potentials can be recorded from the microchannel-based peripheral neural interface; a critical requirement for any neural interface intended to facilitate direct neural control of external technologies.

Neuroprotection mediated by inhibition of calpain during acute viral encephalitis

PubMed Central

Howe, Charles L.; LaFrance-Corey, Reghann G.; Mirchia, Kanish; Sauer, Brian M.; McGovern, Renee M.; Reid, Joel M.; Buenz, Eric J.

2016-01-01

Neurologic complications associated with viral encephalitis, including seizures and cognitive impairment, are a global health issue, especially in children. We previously showed that hippocampal injury during acute picornavirus infection in mice is associated with calpain activation and is the result of neuronal death triggered by brain-infiltrating inflammatory monocytes. We therefore hypothesized that treatment with a calpain inhibitor would protect neurons from immune-mediated bystander injury. C57BL/6J mice infected with the Daniel’s strain of Theiler’s murine encephalomyelitis virus were treated with the FDA-approved drug ritonavir using a dosing regimen that resulted in plasma concentrations within the therapeutic range for calpain inhibition. Ritonavir treatment significantly reduced calpain activity in the hippocampus, protected hippocampal neurons from death, preserved cognitive performance, and suppressed seizure escalation, even when therapy was initiated 36 hours after disease onset. Calpain inhibition by ritonavir may be a powerful tool for preserving neurons and cognitive function and preventing neural circuit dysregulation in humans with neuroinflammatory disorders. PMID:27345730

Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons.

PubMed

Lobanova, Anastasia; She, Robert; Pieraut, Simon; Clapp, Charlie; Maximov, Anton; Denchi, Eros Lazzerini

2017-04-01

Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans. © 2017 Lobanova et al.; Published by Cold Spring Harbor Laboratory Press.

Behavioural signatures of backward planning in animals.

PubMed

Afsardeir, Arsham; Keramati, Mehdi

2018-03-01

Goal-directed planning in behavioural and neural sciences is theorized to involve a prospective mental simulation that, starting from the animal's current state in the environment, expands a decision tree in a forward fashion. Backward planning in the artificial intelligence literature, however, suggests that agents expand a mental tree in a backward fashion starting from a certain goal state they have in mind. Here, we show that several behavioural patterns observed in animals and humans, namely outcome-specific Pavlovian-to-instrumental transfer and differential outcome effect, can be parsimoniously explained by backward planning. Our basic assumption is that the presentation of a cue that has been associated with a certain outcome triggers backward planning from that outcome state. On the basis of evidence pointing to forward and backward planning models, we discuss the possibility of brain using a bidirectional planning mechanism where forward and backward trees are expanded in parallel to achieve higher efficiency. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The brain-computer interface cycle.

PubMed

van Gerven, Marcel; Farquhar, Jason; Schaefer, Rebecca; Vlek, Rutger; Geuze, Jeroen; Nijholt, Anton; Ramsey, Nick; Haselager, Pim; Vuurpijl, Louis; Gielen, Stan; Desain, Peter

2009-08-01

Brain-computer interfaces (BCIs) have attracted much attention recently, triggered by new scientific progress in understanding brain function and by impressive applications. The aim of this review is to give an overview of the various steps in the BCI cycle, i.e., the loop from the measurement of brain activity, classification of data, feedback to the subject and the effect of feedback on brain activity. In this article we will review the critical steps of the BCI cycle, the present issues and state-of-the-art results. Moreover, we will develop a vision on how recently obtained results may contribute to new insights in neurocognition and, in particular, in the neural representation of perceived stimuli, intended actions and emotions. Now is the right time to explore what can be gained by embracing real-time, online BCI and by adding it to the set of experimental tools already available to the cognitive neuroscientist. We close by pointing out some unresolved issues and present our view on how BCI could become an important new tool for probing human cognition.

CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination.

PubMed

Marjanović, Marko; Sánchez-Huertas, Carlos; Terré, Berta; Gómez, Rocío; Scheel, Jan Frederik; Pacheco, Sarai; Knobel, Philip A; Martínez-Marchal, Ana; Aivio, Suvi; Palenzuela, Lluís; Wolfrum, Uwe; McKinnon, Peter J; Suja, José A; Roig, Ignasi; Costanzo, Vincenzo; Lüders, Jens; Stracker, Travis H

2015-07-09

CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63-deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death, and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63-deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination.

CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination

PubMed Central

Marjanović, Marko; Sánchez-Huertas, Carlos; Terré, Berta; Gómez, Rocío; Scheel, Jan Frederik; Pacheco, Sarai; Knobel, Philip A.; Martínez-Marchal, Ana; Aivio, Suvi; Palenzuela, Lluís; Wolfrum, Uwe; McKinnon, Peter J.; Suja, José A.; Roig, Ignasi; Costanzo, Vincenzo; Lüders, Jens; Stracker, Travis H.

2015-01-01

CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63 deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63 deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination. PMID:26158450

Translating Dosage Compensation to Trisomy 21

PubMed Central

Jiang, Jun; Jing, Yuanchun; Cost, Gregory J.; Chiang, Jen-Chieh; Kolpa, Heather J.; Cotton, Allison M.; Carone, Dawn M.; Carone, Benjamin R.; Shivak, David A.; Guschin, Dmitry Y.; Pearl, Jocelynn R.; Rebar, Edward J.; Byron, Meg; Gregory, Philip D.; Brown, Carolyn J.; Urnov, Fyodor D.; Hall, Lisa L.; Lawrence, Jeanne B.

2013-01-01

Down syndrome (DS) is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21 (Chr21). We tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST. Using genome editing with zinc finger nucleases, we targeted a large, inducible XIST transgene into the Chr21 DYRK1A locus, in DS pluripotent stem cells. XIST RNA coats Chr21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a “Chr21 Barr Body.” This provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise. Remarkably, deficits in proliferation and neural rosette formation are rapidly reversed upon silencing one Chr21. Successful trisomy silencing in vitro also surmounts the major first step towards potential development of “chromosome therapy”. PMID:23863942

Chemosensors in the Nose: Guardians of the Airways

PubMed Central

Tizzano, Marco

2013-01-01

The G-protein-coupled receptor molecules and downstream effectors that are used by taste buds to detect sweet, bitter, and savory tastes are also utilized by chemoresponsive cells of the airways to detect irritants. Here, we describe the different cell types in the airways that utilize taste-receptor signaling to trigger protective epithelial and neural responses to potentially dangerous toxins and bacterial infection. PMID:23280357

Methodologies for the assessment of earthquake-triggered landslides hazard. A comparison of Logistic Regression and Artificial Neural Network models.

NASA Astrophysics Data System (ADS)

García-Rodríguez, M. J.; Malpica, J. A.; Benito, B.

2009-04-01

In recent years, interest in landslide hazard assessment studies has increased substantially. They are appropriate for evaluation and mitigation plan development in landslide-prone areas. There are several techniques available for landslide hazard research at a regional scale. Generally, they can be classified in two groups: qualitative and quantitative methods. Most of qualitative methods tend to be subjective, since they depend on expert opinions and represent hazard levels in descriptive terms. On the other hand, quantitative methods are objective and they are commonly used due to the correlation between the instability factors and the location of the landslides. Within this group, statistical approaches and new heuristic techniques based on artificial intelligence (artificial neural network (ANN), fuzzy logic, etc.) provide rigorous analysis to assess landslide hazard over large regions. However, they depend on qualitative and quantitative data, scale, types of movements and characteristic factors used. We analysed and compared an approach for assessing earthquake-triggered landslides hazard using logistic regression (LR) and artificial neural networks (ANN) with a back-propagation learning algorithm. One application has been developed in El Salvador, a country of Central America where the earthquake-triggered landslides are usual phenomena. In a first phase, we analysed the susceptibility and hazard associated to the seismic scenario of the 2001 January 13th earthquake. We calibrated the models using data from the landslide inventory for this scenario. These analyses require input variables representing physical parameters to contribute to the initiation of slope instability, for example, slope gradient, elevation, aspect, mean annual precipitation, lithology, land use, and terrain roughness, while the occurrence or non-occurrence of landslides is considered as dependent variable. The results of the landslide susceptibility analysis are checked using landslide location data. These results show a high concordance between the landslide inventory and the high susceptibility estimated zone with an adjustment of 95.1 % for ANN model and 89.4% for LR model. In addition, we make a comparative analysis of both techniques using the Receiver Operating Characteristic (ROC) curve, a graphical plot of the sensitivity vs. (1 - specificity) for a binary classifier system in function of its discrimination threshold, and calculating the Area Under the ROC (AUROC) value for each model. Finally, the previous models are used for the developing a new probabilistic landslide hazard map for future events. They are obtained combining the expected triggering factor (calculated earthquake ground motion) for a return period of 475 years with the susceptibility map.

Exfoliated Human Olfactory Neuroepithelium: A Source of Neural Progenitor Cells.

PubMed

Jiménez-Vaca, Ana L; Benitez-King, Gloria; Ruiz, Víctor; Ramírez-Rodríguez, Gerardo B; Hernández-de la Cruz, Beatriz; Salamanca-Gómez, Fabio A; González-Márquez, Humberto; Ramírez-Sánchez, Israel; Ortíz-López, Leonardo; Vélez-Del Valle, Cristina; Ordoñez-Razo, Rosa Ma

2018-03-01

Neural progenitor cells (NPC) contained in the human adult olfactory neuroepithelium (ONE) possess an undifferentiated state, the capability of self-renewal, the ability to generate neural and glial cells as well as being kept as neurospheres in cell culture conditions. Recently, NPC have been isolated from human or animal models using high-risk surgical methods. Therefore, it was necessary to improve methodologies to obtain and maintain human NPC as well as to achieve better knowledge of brain disorders. In this study, we propose the establishment and characterization of NPC cultures derived from the human olfactory neuroepithelium, using non-invasive procedures. Twenty-two healthy individuals (29.7 ± 4.5 years of age) were subjected to nasal exfoliation. Cells were recovered and kept as neurospheres under serum-free conditions. The neural progenitor origin of these neurospheres was determined by immunocytochemistry and qPCR. Their ability for self-renewal and multipotency was analyzed by clonogenic and differentiation assays, respectively. In the cultures, the ONE cells preserved the phenotype of the neurospheres. The expression levels of Nestin, Musashi, Sox2, and βIII-tubulin demonstrated the neural origin of the neurospheres; 48% of the cells separated could generate neurospheres, determining that they retained their self-renewal capacity. Neurospheres were differentiated in the absence of growth factors (EGF and FGF), and their multipotency ability was maintained as well. We were also able to isolate and grow human neural progenitor cells (neurospheres) through nasal exfoliates (non-invasive method) of the ONE from healthy adults, which is an extremely important contribution for the study of brain disorders and for the development of new therapies.

EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs.

PubMed

Ebert, Allison D; Shelley, Brandon C; Hurley, Amanda M; Onorati, Marco; Castiglioni, Valentina; Patitucci, Teresa N; Svendsen, Soshana P; Mattis, Virginia B; McGivern, Jered V; Schwab, Andrew J; Sareen, Dhruv; Kim, Ho Won; Cattaneo, Elena; Svendsen, Clive N

2013-05-01

We have developed a simple method to generate and expand multipotent, self-renewing pre-rosette neural stem cells from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) without utilizing embryoid body formation, manual selection techniques, or complex combinations of small molecules. Human ESC and iPSC colonies were lifted and placed in a neural stem cell medium containing high concentrations of EGF and FGF-2. Cell aggregates (termed EZ spheres) could be expanded for long periods using a chopping method that maintained cell-cell contact. Early passage EZ spheres rapidly down-regulated OCT4 and up-regulated SOX2 and nestin expression. They retained the potential to form neural rosettes and consistently differentiated into a range of central and peripheral neural lineages. Thus, they represent a very early neural stem cell with greater differentiation flexibility than other previously described methods. As such, they will be useful for the rapidly expanding field of neurological development and disease modeling, high-content screening, and regenerative therapies based on pluripotent stem cell technology. Copyright © 2013 Elsevier B.V. All rights reserved.

The precuneus may encode irrationality in human gambling.

PubMed

Sacre, P; Kerr, M S D; Subramanian, S; Kahn, K; Gonzalez-Martinez, J; Johnson, M A; Sarma, S V; Gale, J T

2016-08-01

Humans often make irrational decisions, especially psychiatric patients who have dysfunctional cognitive and emotional circuitry. Understanding the neural basis of decision-making is therefore essential towards patient management, yet current studies suffer from several limitations. Functional magnetic resonance imaging (fMRI) studies in humans have dominated decision-making neuroscience, but have poor temporal resolution and the blood oxygenation level-dependent signal is only a proxy for neural activity. On the other hand, lesion studies in humans used to infer functionality in decision-making lack characterization of neural activity altogether. Using a combination of local field potential recordings in human subjects performing a financial decision-making task, spectral analyses, and non-parametric cluster statistics, we analyzed the activity in the precuneus. In nine subjects, the neural activity modulated significantly between rational and irrational trials in the precuneus (p <; 0.001). In particular, high-frequency activity (70-100 Hz) increased when irrational decisions were made. Although preliminary, these results suggest suppression of gamma rhythms via electrical stimulation in the precuneus as a therapeutic intervention for pathological decision-making.

Recycling signals in the neural crest.

PubMed

Taneyhill, Lisa A; Bronner-Fraser, Marianne

2005-01-01

Vertebrate neural crest cells are multipotent and differentiate into structures that include cartilage and the bones of the face, as well as much of the peripheral nervous system. Understanding how different model vertebrates utilize signaling pathways reiteratively during various stages of neural crest formation and differentiation lends insight into human disorders associated with the neural crest.

Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

PubMed

Marsden, Karen E; Ma, Wei Ji; Deci, Edward L; Ryan, Richard M; Chiu, Pearl H

2015-06-01

The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic).

Molecular stages of rapid and uniform neuralization of human embryonic stem cells.

PubMed

Bajpai, R; Coppola, G; Kaul, M; Talantova, M; Cimadamore, F; Nilbratt, M; Geschwind, D H; Lipton, S A; Terskikh, A V

2009-06-01

Insights into early human development are fundamental for our understanding of human biology. Efficient differentiation of human embryonic stem cells (hESCs) into neural precursor cells is critical for future cell-based therapies. Here, using defined conditions, we characterized a new method for rapid and uniform differentiation of hESCs into committed neural precursor cells (designated C-NPCs). Dynamic gene expression analysis identified several distinct stages of ESC neuralization and revealed functional modules of coregulated genes and pathways. The first wave of gene expression changes, likely corresponding to the transition through primitive ectoderm, started at day 3, preceding the formation of columnar neuroepithelial rosettes. The second wave started at day 5, coinciding with the formation of rosettes. The majority of C-NPCs were positive for both anterior and posterior markers of developing neuroepithelium. In culture, C-NPCs became electrophysiologically functional neurons; on transplantation into neonatal mouse brains, C-NPCs integrated into the cortex and olfactory bulb, acquiring appropriate neuronal morphologies and markers. Compared to rosette-NPCs,(1) C-NPCs exhibited limited in vitro expansion capacity and did not express potent oncogenes such as PLAG1 or RSPO3. Concordantly, we never detected tumors or excessive neural proliferation after transplantation of C-NPCs into mouse brains. In conclusion, our study provides a framework for future analysis of molecular signaling during ESC neuralization.

The development of the neural crest in the human

PubMed Central

O’Rahilly, Ronan; Müller, Fabiola

2007-01-01

The first systematic account of the neural crest in the human has been prepared after an investigation of 185 serially sectioned staged embryos, aided by graphic reconstructions. As many as fourteen named topographical subdivisions of the crest were identified and eight of them give origin to ganglia (Table 2). Significant findings in the human include the following. (1) An indication of mesencephalic neural crest is discernible already at stage 9, and trigeminal, facial, and postotic components can be detected at stage 10. (2) Crest was not observed at the level of diencephalon 2. Although pre-otic crest from the neural folds is at first continuous (stage 10), crest-free zones are soon observable (stage 11) in Rh.1, 3, and 5. (3) Emigration of cranial neural crest from the neural folds at the neurosomatic junction begins before closure of the rostral neuropore, and later crest cells do not accumulate above the neural tube. (4) The trigeminal, facial, glossopharyngeal and vagal ganglia, which develop from crest that emigrates before the neural folds have fused, continue to receive contributions from the roof plate of the neural tube after fusion of the folds. (5) The nasal crest and the terminalis-vomeronasal complex are the last components of the cranial crest to appear (at stage 13) and they persist longer. (6) The optic, mesencephalic, isthmic, accessory, and hypoglossal crest do not form ganglia. Cervical ganglion 1 is separated early from the neural crest and is not a Froriep ganglion. (7) The cranial ganglia derived from neural crest show a specific relationship to individual neuromeres, and rhombomeres are better landmarks than the otic primordium, which descends during stages 9–14. (8) Epipharyngeal placodes of the pharyngeal arches contribute to cranial ganglia, although that of arch 1 is not typical. (9) The neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there rostrad to the truncus arteriosus at stage 12 is identified here, for the first time in the human, as the cardiac crest. (10) The hypoglossal crest provides cells that accompany those of myotomes 1–4 and form the hypoglossal cell cord at stages 13 and 14. (11) The occipital crest, which is related to somites 1–4 in the human, differs from the spinal mainly in that it does not develop ganglia. (12) The occipital and spinal portions of the crest migrate dorsoventrad and appear to traverse the sclerotomes before the differentiation into loose and dense zones in the latter. (13) Embryonic examples of synophthalmia and anencephaly are cited to emphasize the role of the neural crest in the development of cranial ganglia and the skull. PMID:17848161

Development of Open Brain Simulator for Human Biomechatronics

NASA Astrophysics Data System (ADS)

Otake, Mihoko; Takagi, Toshihisa; Asama, Hajime

Modeling and simulation based on mechanisms is important in order to design and control mechatronic systems. In particular, in-depth understanding and realistic modeling of biological systems is indispensable for biomechatronics. This paper presents open brain simulator, which estimates the neural state of human through external measurement for the purpose of improving motor and social skills. Macroscopic anatomical nervous systems model was built which can be connected to the musculoskeletal model. Microscopic anatomical and physiological neural models were interfaced to the macroscopic model. Neural activities of somatosensory area and Purkinje cell were calculated from motion capture data. The simulator provides technical infrastructure for human biomechatronics, which is promising for the novel diagnosis of neurological disorders and their treatments through medication and movement therapy, and for motor learning support system supporting acquisition of motor skill considering neural mechanism.

Characterization of Human Neural Progenitor Cell Models for Developmental Neurotoxicity Screening

EPA Science Inventory

Current testing methods for developmental neurotoxicity (DNT) make evaluation of the effects of large numbers of chemicals impractical and prohibitively expensive. As such, we are evaluating two different human neural progenitor cell (hNPC) models for their utility in screens for...

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

PubMed

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.

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

PubMed

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.

Shades of grey; Assessing the contribution of the magno- and parvocellular systems to neural processing of the retinal input in the human visual system from the influence of neural population size and its discharge activity on the VEP.

PubMed

Marcar, Valentine L; Baselgia, Silvana; Lüthi-Eisenegger, Barbara; Jäncke, Lutz

2018-03-01

Retinal input processing in the human visual system involves a phasic and tonic neural response. We investigated the role of the magno- and parvocellular systems by comparing the influence of the active neural population size and its discharge activity on the amplitude and latency of four VEP components. We recorded the scalp electric potential of 20 human volunteers viewing a series of dartboard images presented as a pattern reversing and pattern on-/offset stimulus. These patterns were designed to vary both neural population size coding the temporal- and spatial luminance contrast property and the discharge activity of the population involved in a systematic manner. When the VEP amplitude reflected the size of the neural population coding the temporal luminance contrast property of the image, the influence of luminance contrast followed the contrast response function of the parvocellular system. When the VEP amplitude reflected the size of the neural population responding to the spatial luminance contrast property the image, the influence of luminance contrast followed the contrast response function of the magnocellular system. The latencies of the VEP components examined exhibited the same behavior across our stimulus series. This investigation demonstrates the complex interplay of the magno- and parvocellular systems on the neural response as captured by the VEP. It also demonstrates a linear relationship between stimulus property, neural response, and the VEP and reveals the importance of feedback projections in modulating the ongoing neural response. In doing so, it corroborates the conclusions of our previous study.

Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception

PubMed Central

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

Video-based convolutional neural networks for activity recognition from robot-centric videos

NASA Astrophysics Data System (ADS)

Ryoo, M. S.; Matthies, Larry

2016-05-01

In this evaluation paper, we discuss convolutional neural network (CNN)-based approaches for human activity recognition. In particular, we investigate CNN architectures designed to capture temporal information in videos and their applications to the human activity recognition problem. There have been multiple previous works to use CNN-features for videos. These include CNNs using 3-D XYT convolutional filters, CNNs using pooling operations on top of per-frame image-based CNN descriptors, and recurrent neural networks to learn temporal changes in per-frame CNN descriptors. We experimentally compare some of these different representatives CNNs while using first-person human activity videos. We especially focus on videos from a robots viewpoint, captured during its operations and human-robot interactions.

Biological neural networks as model systems for designing future parallel processing computers

NASA Technical Reports Server (NTRS)

Ross, Muriel D.

1991-01-01

One of the more interesting debates of the present day centers on whether human intelligence can be simulated by computer. The author works under the premise that neurons individually are not smart at all. Rather, they are physical units which are impinged upon continuously by other matter that influences the direction of voltage shifts across the units membranes. It is only the action of a great many neurons, billions in the case of the human nervous system, that intelligent behavior emerges. What is required to understand even the simplest neural system is painstaking analysis, bit by bit, of the architecture and the physiological functioning of its various parts. The biological neural network studied, the vestibular utricular and saccular maculas of the inner ear, are among the most simple of the mammalian neural networks to understand and model. While there is still a long way to go to understand even this most simple neural network in sufficient detail for extrapolation to computers and robots, a start was made. Moreover, the insights obtained and the technologies developed help advance the understanding of the more complex neural networks that underlie human intelligence.

Neural codes of seeing architectural styles

PubMed Central

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

2017-01-01

Images of iconic buildings, such as the CN Tower, instantly transport us to specific places, such as Toronto. Despite the substantial impact of architectural design on people’s visual experience of built environments, we know little about its neural representation in the human brain. In the present study, we have found patterns of neural activity associated with specific architectural styles in several high-level visual brain regions, but not in primary visual cortex (V1). This finding suggests that the neural correlates of the visual perception of architectural styles stem from style-specific complex visual structure beyond the simple features computed in V1. Surprisingly, the network of brain regions representing architectural styles included the fusiform face area (FFA) in addition to several scene-selective regions. Hierarchical clustering of error patterns further revealed that the FFA participated to a much larger extent in the neural encoding of architectural styles than entry-level scene categories. We conclude that the FFA is involved in fine-grained neural encoding of scenes at a subordinate-level, in our case, architectural styles of buildings. This study for the first time shows how the human visual system encodes visual aspects of architecture, one of the predominant and longest-lasting artefacts of human culture. PMID:28071765

Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

PubMed Central

Varela, Christine; Denis, Jérôme Alexandre; Polentes, Jérôme; Feyeux, Maxime; Aubert, Sophie; Champon, Benoite; Piétu, Geneviève; Peschanski, Marc; Lefort, Nathalie

2012-01-01

Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines. PMID:22269325

Neural codes of seeing architectural styles.

PubMed

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

2017-01-10

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

An Implantable Wireless Neural Interface for Recording Cortical Circuit Dynamics in Moving Primates

PubMed Central

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

2013-01-01

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 MEA via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1Hz to 7.8kHz, ×200 gain) and multiplexed by a custom application specific integrated circuit, digitized, and then packaged for transmission. The neural data (24 Mbps) was transmitted by a wireless data link carried on an frequency shift key modulated signal at 3.2GHz and 3.8GHz to a receiver 1 meter 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-hour continuous operation between recharge via an inductive transcutaneous wireless power link at 2MHz. Main results Device verification and early validation was 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 on how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile patient use, have the potential for wider diagnosis of neurological conditions, and will advance brain research. PMID:23428937

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

NASA Astrophysics Data System (ADS)

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 patient use, have the potential for wider diagnosis of neurological conditions and will advance brain research.

Chronic pain. Decreased motivation during chronic pain requires long-term depression in the nucleus accumbens.

PubMed

Schwartz, Neil; Temkin, Paul; Jurado, Sandra; Lim, Byung Kook; Heifets, Boris D; Polepalli, Jai S; Malenka, Robert C

2014-08-01

Several symptoms associated with chronic pain, including fatigue and depression, are characterized by reduced motivation to initiate or complete goal-directed tasks. However, it is unknown whether maladaptive modifications in neural circuits that regulate motivation occur during chronic pain. Here, we demonstrate that the decreased motivation elicited in mice by two different models of chronic pain requires a galanin receptor 1-triggered depression of excitatory synaptic transmission in indirect pathway nucleus accumbens medium spiny neurons. These results demonstrate a previously unknown pathological adaption in a key node of motivational neural circuitry that is required for one of the major sequela of chronic pain states and syndromes. Copyright © 2014, American Association for the Advancement of Science.

Vestibulo-Sympathetic Responses

PubMed Central

Yates, Bill J; Bolton, Philip S.; Macefield, Vaughan G.

2014-01-01

Evidence accumulated over 30 years, from experiments on animals and human subjects, has conclusively demonstrated that inputs from the vestibular otolith organs contribute to the control of blood pressure during movement and changes in posture. This review considers the effects of gravity on the body axis, and the consequences of postural changes on blood distribution in the body. It then separately considers findings collected in experiments on animals and human subjects demonstrating that the vestibular system regulates blood distribution in the body during movement. Vestibulosympathetic reflexes differ from responses triggered by unloading of cardiovascular receptors such as baroreceptors and cardiopulmonary receptors, as they can be elicited before a change in blood distribution occurs in the body. Dissimilarities in the expression of vestibulosympathetic reflexes in humans and animals are also described. In particular, there is evidence from experiments in animals, but not humans, that vestibulosympathetic reflexes are patterned, and differ between body regions. Results from neurophysiological and neuroanatomical studies in animals are discussed that identify the neurons that mediate vestibulosympathetic responses, which include cells in the caudal aspect of the vestibular nucleus complex, interneurons in the lateral medullary reticular formation, and bulbospinal neurons in the rostral ventrolateral medulla (RVLM). Recent findings showing that cognition can modify the gain of vestibulosympathetic responses are also presented, and neural pathways that could mediate adaptive plasticity in the responses are proposed, including connections of the posterior cerebellar vermis with the vestibular nuclei and brainstem nuclei that regulate blood pressure. PMID:24715571

Oxytocin, brain physiology, and functional connectivity: a review of intranasal oxytocin fMRI studies.

PubMed

Bethlehem, Richard A I; van Honk, Jack; Auyeung, Bonnie; Baron-Cohen, Simon

2013-07-01

In recent years the neuropeptide oxytocin (OT) has become one of the most studied peptides of the human neuroendocrine system. Research has shown widespread behavioural effects and numerous potential therapeutic benefits. However, little is known about how OT triggers these effects in the brain. Here, we discuss some of the physiological properties of OT in the human brain including the long half-life of neuropeptides, the diffuse projections of OT throughout the brain and interactions with other systems such as the dopaminergic system. These properties indicate that OT acts without clear spatial and temporal specificity. Therefore, it is likely to have widespread effects on the brain's intrinsic functioning. Additionally, we review studies that have used functional magnetic resonance imaging (fMRI) concurrently with OT administration. These studies reveal a specific set of 'social' brain regions that are likely to be the strongest targets for OT's potential to influence human behaviour. On the basis of the fMRI literature and the physiological properties of the neuropeptide, we argue that OT has the potential to not only modulate activity in a set of specific brain regions, but also the functional connectivity between these regions. In light of the increasing knowledge of the behavioural effects of OT in humans, studies of the effects of OT administration on brain function can contribute to our understanding of the neural networks in the social brain. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-11-01

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

Diurnal and twenty-four hour patterning of human diseases: acute and chronic common and uncommon medical conditions.

PubMed

Smolensky, Michael H; Portaluppi, Francesco; Manfredini, Roberto; Hermida, Ramon C; Tiseo, Ruana; Sackett-Lundeen, Linda L; Haus, Erhard L

2015-06-01

The symptom intensity and mortality of human diseases, conditions, and syndromes exhibit diurnal or 24 h patterning, e.g., skin: atopic dermatitis, urticaria, psoriasis, and palmar hyperhidrosis; gastrointestinal: esophageal reflux, peptic ulcer (including perforation and hemorrhage), cyclic vomiting syndrome, biliary colic, hepatic variceal hemorrhage, and proctalgia fugax; infection: susceptibility, fever, and mortality; neural: frontal, parietal, temporal, and occipital lobe seizures, Parkinson's and Alzheimer's disease, hereditary progressive dystonia, and pain (cancer, post-surgical, diabetic neuropathic and foot ulcer, tooth caries, burning mouth and temporomandibular syndromes, fibromyalgia, sciatica, intervertebral vacuum phenomenon, multiple sclerosis muscle spasm, and migraine, tension, cluster, hypnic, and paroxysmal hemicranial headache); renal: colic and nocturnal enuresis and polyuria; ocular: bulbar conjunctival redness, keratoconjunctivitis sicca, intraocular pressure and anterior ischemic optic neuropathy, and recurrent corneal erosion syndrome; psychiatric/behavioral: major and seasonal affective depressive disorders, bipolar disorder, parasuicide and suicide, dementia-associated agitation, and addictive alcohol, tobacco, and heroin cravings and withdrawal phenomena; plus autoimmune and musculoskeletal: rheumatoid arthritis, osteoarthritis, axial spondylarthritis, gout, Sjögren's syndrome, and systemic lupus erythematosus. Knowledge of these and other 24 h patterns of human pathophysiology informs research of their underlying circadian and other endogenous mechanisms, external temporal triggers, and more effective patient care entailing clinical chronopreventive and chronotherapeutic strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Connecting the Brain to Itself through an Emulation

PubMed Central

Serruya, Mijail D.

2017-01-01

Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as in vitro culture preparations or in vivo ectopic construct organoids. Arrays of modules can be constructed as early stage whole brain emulators, following canonical intra- and inter-regional circuits. By using machine learning algorithms and classic tasks known to activate quasi-orthogonal functional connectivity patterns, bedside testing can rapidly identify ensemble tuning properties and in turn cycle through a sequence of external module architectures to explore which can causatively alter perception and behavior. Whole brain emulation both (1) serves to augment human neural function, compensating for disease and injury as an auxiliary parallel system, and (2) has its independent operation bootstrapped by a human-in-the-loop to identify optimal micro- and macro-architectures, update synaptic weights, and entrain behaviors. In this manner, closed-loop brain-computer interface pilot clinical trials can advance strong artificial intelligence development and forge new therapies to restore independence in children and adults with neurological conditions. PMID:28713235

Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid.

PubMed

Frisca, Frisca; Crombie, Duncan E; Dottori, Mirella; Goldshmit, Yona; Pébay, Alice

2013-05-01

We previously reported that lysophosphatidic acid (LPA) inhibits the neuronal differentiation of human embryonic stem cells (hESC). We extended these studies by analyzing LPA's effects on the expansion of neural stem/progenitor cells (NS/PC) derived from hESCs and human induced pluripotent stem cells (iPSC), and we assessed whether data obtained on the neural differentiation of hESCs were relevant to iPSCs. We showed that hESCs and iPSCs exhibited comparable mRNA expression profiles of LPA receptors and producing enzymes upon neural differentiation. We demonstrated that LPA inhibited the expansion of NS/PCs of both origins, mainly by increased apoptosis in a Rho/Rho-associated kinase (ROCK)-dependent mechanism. Furthermore, LPA inhibited the neuronal differentiation of iPSCs. Lastly, LPA induced neurite retraction of NS/PC-derived early neurons through Rho/ROCK, which was accompanied by myosin light chain (MLC) phosphorylation. Our data demonstrate the consistency of LPA effects across various sources of human NS/PCs, rendering hESCs and iPSCs valuable models for studying lysophospholipid signaling in human neural cells. Our data also highlight the importance of the Rho/ROCK pathway in human NS/PCs. As LPA levels are increased in the central nervous system (CNS) following injury, LPA-mediated effects on NS/PCs and early neurons could contribute to the poor neurogenesis observed in the CNS following injury.

The efficacy of using human myoelectric signals to control the limbs of robots in space

NASA Technical Reports Server (NTRS)

Clark, Jane E.; Phillips, Sally J.

1988-01-01

This project was designed to investigate the usefulness of the myoelectric signal as a control in robotics applications. More specifically, the neural patterns associated with human arm and hand actions were studied to determine the efficacy of using these myoelectric signals to control the manipulator arm of a robot. The advantage of this approach to robotic control was the use of well-defined and well-practiced neural patterns already available to the system, as opposed to requiring the human operator to learn new tasks and establish new neural patterns in learning to control a joystick or mechanical coupling device.

Functional Roles of Neural Preparatory Processes in a Cued Stroop Task Revealed by Linking Electrophysiology with Behavioral Performance.

PubMed

Wang, Chao; Ding, Mingzhou; Kluger, Benzi M

2015-01-01

It is well established that cuing facilitates behavioral performance and that different aspects of instructional cues evoke specific neural preparatory processes in cued task-switching paradigms. To deduce the functional role of these neural preparatory processes the majority of studies vary aspects of the experimental paradigm and describe how these variations alter markers of neural preparatory processes. Although these studies provide important insights, they also have notable limitations, particularly in terms of understanding the causal or functional relationship of neural markers to cognitive and behavioral processes. In this study, we sought to address these limitations and uncover the functional roles of neural processes by examining how variability in the amplitude of neural preparatory processes predicts behavioral performance to subsequent stimuli. To achieve this objective 16 young adults were recruited to perform a cued Stroop task while their brain activity was measured using high-density electroencephalography. Four temporally overlapping but functionally and topographically distinct cue-triggered event related potentials (ERPs) were identified: 1) A left-frontotemporal negativity (250-700 ms) that was positively associated with word-reading performance; 2) a midline-frontal negativity (450-800 ms) that was positively associated with color-naming and incongruent performance; 3) a left-frontal negativity (450-800 ms) that was positively associated with switch trial performance; and 4) a centroparietal positivity (450-800 ms) that was positively associated with performance for almost all trial types. These results suggest that at least four dissociable cognitive processes are evoked by instructional cues in the present task, including: 1) domain-specific task facilitation; 2) switch-specific task-set reconfiguration; 3) preparation for response conflict; and 4) proactive attentional control. Examining the relationship between ERPs and behavioral performance provides a functional link between neural markers and the cognitive processes they index.

Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation.

PubMed

Huang, Zijing; Zhou, Tian; Sun, Xiaowei; Zheng, Yingfeng; Cheng, Bing; Li, Mei; Liu, Xialin; He, Chang

2018-01-01

Inflammation has emerged to be a critical mechanism responsible for neural damage and neurodegenerative diseases. Microglia, the resident innate immune cells in retina, are implicated as principal components of the immunological insult to retinal neural cells. The involvement of microglia in retinal inflammation is complex and here we propose for the first time that necroptosis in microglia triggers neuroinflammation and exacerbates retinal neural damage and degeneration. We found microglia experienced receptor-interacting protein kinase 1 (RIP1)- and RIP3-dependent necroptosis not only in the retinal degenerative rd1 mice, but also in the acute retinal neural injury mice. The necroptotic microglia released various pro-inflammatory cytokines and chemokines, such as tumor necrosis factor-α and chemokine (C-C motif) ligand 2, which orchestrated the retinal inflammation. Importantly, necroptosis blockade using necrostatin-1 could suppress microglia-mediated inflammation, rescue retinal degeneration or prevent neural injury in vivo. Meanwhile, cultured microglia underwent RIP1/3-mediated necroptosis and the necroptotic microglia produced large amounts of pro-inflammatory cytokines in response to lipopolysaccharide or oxidative stress in vitro. Mechanically, TLR4 deficiency ameliorated microglia necroptosis with decreased expression levels of machinery molecules RIP1 and RIP3, and suppressed retinal inflammation, suggesting that TLR4 signaling was required in microglia necroptosis-mediated inflammation. Thus, we proposed that microglia experienced necroptosis through TLR4 activation, promoting an inflammatory response that serves to exacerbate considerable neural damage and degeneration. Necroptosis blockade therefore emerged as a novel therapeutic strategy for tempering microglia-mediated neuroinflammation and ameliorating neural injury and neurodegenerative diseases.

Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation

PubMed Central

Huang, Zijing; Zhou, Tian; Sun, Xiaowei; Zheng, Yingfeng; Cheng, Bing; Li, Mei; Liu, Xialin; He, Chang

2018-01-01

Inflammation has emerged to be a critical mechanism responsible for neural damage and neurodegenerative diseases. Microglia, the resident innate immune cells in retina, are implicated as principal components of the immunological insult to retinal neural cells. The involvement of microglia in retinal inflammation is complex and here we propose for the first time that necroptosis in microglia triggers neuroinflammation and exacerbates retinal neural damage and degeneration. We found microglia experienced receptor-interacting protein kinase 1 (RIP1)- and RIP3-dependent necroptosis not only in the retinal degenerative rd1 mice, but also in the acute retinal neural injury mice. The necroptotic microglia released various pro-inflammatory cytokines and chemokines, such as tumor necrosis factor-α and chemokine (C-C motif) ligand 2, which orchestrated the retinal inflammation. Importantly, necroptosis blockade using necrostatin-1 could suppress microglia-mediated inflammation, rescue retinal degeneration or prevent neural injury in vivo. Meanwhile, cultured microglia underwent RIP1/3-mediated necroptosis and the necroptotic microglia produced large amounts of pro-inflammatory cytokines in response to lipopolysaccharide or oxidative stress in vitro. Mechanically, TLR4 deficiency ameliorated microglia necroptosis with decreased expression levels of machinery molecules RIP1 and RIP3, and suppressed retinal inflammation, suggesting that TLR4 signaling was required in microglia necroptosis-mediated inflammation. Thus, we proposed that microglia experienced necroptosis through TLR4 activation, promoting an inflammatory response that serves to exacerbate considerable neural damage and degeneration. Necroptosis blockade therefore emerged as a novel therapeutic strategy for tempering microglia-mediated neuroinflammation and ameliorating neural injury and neurodegenerative diseases. PMID:28885615

Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network

PubMed Central

Chen, Yu-Chen; Li, Xiaowei; Liu, Lijie; Wang, Jian; Lu, Chun-Qiang; Yang, Ming; Jiao, Yun; Zang, Feng-Chao; Radziwon, Kelly; Chen, Guang-Di; Sun, Wei; Krishnan Muthaiah, Vijaya Prakash; Salvi, Richard; Teng, Gao-Jun

2015-01-01

Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus–hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed. DOI: http://dx.doi.org/10.7554/eLife.06576.001 PMID:25962854

Neural correlates of math anxiety - an overview and implications.

PubMed

Artemenko, Christina; Daroczy, Gabriella; Nuerk, Hans-Christoph

2015-01-01

Math anxiety is a common phenomenon which can have a negative impact on numerical and arithmetic performance. However, so far little is known about the underlying neurocognitive mechanisms. This mini review provides an overview of studies investigating the neural correlates of math anxiety which provide several hints regarding its influence on math performance: while behavioral studies mostly observe an influence of math anxiety on difficult math tasks, neurophysiological studies show that processing efficiency is already affected in basic number processing. Overall, the neurocognitive literature suggests that (i) math anxiety elicits emotion- and pain-related activation during and before math activities, (ii) that the negative emotional response to math anxiety impairs processing efficiency, and (iii) that math deficits triggered by math anxiety may be compensated for by modulating the cognitive control or emotional regulation network. However, activation differs strongly between studies, depending on tasks, paradigms, and samples. We conclude that neural correlates can help to understand and explore the processes underlying math anxiety, but the data are not very consistent yet.

Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders.

PubMed

Jaiswal, Preeti; Mohanakumar, Kochupurackal P; Rajamma, Usha

2015-08-01

Serotonergic system has long been implicated in the aetiology of autism spectrum disorders (ASD), since platelet hyperserotonemia is consistently observed in a subset of autistic patients, who respond well to selective serotonin reuptake inhibitors. Apart from being a neurotransmitter, serotonin functions as a neurotrophic factor directing brain development and as an immunoregulator modulating immune responses. Serotonin transporter (SERT) regulates serotonin level in lymphoid tissues to ensure its proper functioning in innate and adaptive responses. Immunological molecules such as cytokines in turn regulate the transcription and activity of SERT. Dysregulation of serotonergic system could trigger signalling cascades that affect normal neural-immune interactions culminating in neurodevelopmental and neural connectivity defects precipitating behavioural abnormalities, or the disease phenotypes. Therefore, we suggest that a better understanding of the cross talk between serotonergic genes, immune systems and serotonergic neurotransmission will open wider avenues to develop pharmacological leads for addressing the core ASD behavioural deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neural correlates of math anxiety – an overview and implications

PubMed Central

Artemenko, Christina; Daroczy, Gabriella; Nuerk, Hans-Christoph

2015-01-01

Math anxiety is a common phenomenon which can have a negative impact on numerical and arithmetic performance. However, so far little is known about the underlying neurocognitive mechanisms. This mini review provides an overview of studies investigating the neural correlates of math anxiety which provide several hints regarding its influence on math performance: while behavioral studies mostly observe an influence of math anxiety on difficult math tasks, neurophysiological studies show that processing efficiency is already affected in basic number processing. Overall, the neurocognitive literature suggests that (i) math anxiety elicits emotion- and pain-related activation during and before math activities, (ii) that the negative emotional response to math anxiety impairs processing efficiency, and (iii) that math deficits triggered by math anxiety may be compensated for by modulating the cognitive control or emotional regulation network. However, activation differs strongly between studies, depending on tasks, paradigms, and samples. We conclude that neural correlates can help to understand and explore the processes underlying math anxiety, but the data are not very consistent yet. PMID:26388824

Learning quadratic receptive fields from neural responses to natural stimuli.

PubMed

Rajan, Kanaka; Marre, Olivier; Tkačik, Gašper

2013-07-01

Models of neural responses to stimuli with complex spatiotemporal correlation structure often assume that neurons are selective for only a small number of linear projections of a potentially high-dimensional input. In this review, we explore recent modeling approaches where the neural response depends on the quadratic form of the input rather than on its linear projection, that is, the neuron is sensitive to the local covariance structure of the signal preceding the spike. To infer this quadratic dependence in the presence of arbitrary (e.g., naturalistic) stimulus distribution, we review several inference methods, focusing in particular on two information theory-based approaches (maximization of stimulus energy and of noise entropy) and two likelihood-based approaches (Bayesian spike-triggered covariance and extensions of generalized linear models). We analyze the formal relationship between the likelihood-based and information-based approaches to demonstrate how they lead to consistent inference. We demonstrate the practical feasibility of these procedures by using model neurons responding to a flickering variance stimulus.

Liking, wanting, and the incentive-sensitization theory of addiction.

PubMed

Berridge, Kent C; Robinson, Terry E

2016-11-01

Rewards are both "liked" and "wanted," and those 2 words seem almost interchangeable. However, the brain circuitry that mediates the psychological process of "wanting" a particular reward is dissociable from circuitry that mediates the degree to which it is "liked." Incentive salience or "wanting," a form of motivation, is generated by large and robust neural systems that include mesolimbic dopamine. By comparison, "liking," or the actual pleasurable impact of reward consumption, is mediated by smaller and fragile neural systems, and is not dependent on dopamine. The incentive-sensitization theory posits the essence of drug addiction to be excessive amplification specifically of psychological "wanting," especially triggered by cues, without necessarily an amplification of "liking." This is because of long-lasting changes in dopamine-related motivation systems of susceptible individuals, called "neural sensitization." A quarter-century after its proposal, evidence has continued to grow in support the incentive-sensitization theory. Further, its scope is now expanding to include diverse behavioral addictions and other psychopathologies. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Liking, Wanting and the Incentive-Sensitization Theory of Addiction

PubMed Central

Berridge, Kent C.; Robinson, Terry E.

2016-01-01

Rewards are both ‘liked’ and ‘wanted’, and those two words seem almost interchangeable. However, the brain circuitry that mediates the psychological process of ‘wanting’ a particular reward is dissociable from circuitry that mediates the degree to which it is ‘liked’. Incentive salience or ‘wanting’, a form of motivation, is generated by large and robust neural systems that include mesolimbic dopamine. By comparison, ‘liking’, or the actual pleasurable impact of reward consumption, is mediated by smaller and fragile neural systems, and is not dependent on dopamine. The incentive-sensitization theory posits the essence of drug addiction to be excessive amplification specifically of psychological ‘wanting’, especially triggered by cues, without necessarily an amplification of ‘liking’. This is due to long-lasting changes in dopamine-related motivation systems of susceptible individuals, called neural sensitization. A quarter-century after its proposal, evidence has continued to grow in support the incentive-sensitization theory. Further, its scope is now expanding to include diverse behavioral addictions and other psychopathologies. PMID:27977239

Neural network face recognition using wavelets

NASA Astrophysics Data System (ADS)

Karunaratne, Passant V.; Jouny, Ismail I.

1997-04-01

The recognition of human faces is a phenomenon that has been mastered by the human visual system and that has been researched extensively in the domain of computer neural networks and image processing. This research is involved in the study of neural networks and wavelet image processing techniques in the application of human face recognition. The objective of the system is to acquire a digitized still image of a human face, carry out pre-processing on the image as required, an then, given a prior database of images of possible individuals, be able to recognize the individual in the image. The pre-processing segment of the system includes several procedures, namely image compression, denoising, and feature extraction. The image processing is carried out using Daubechies wavelets. Once the images have been passed through the wavelet-based image processor they can be efficiently analyzed by means of a neural network. A back- propagation neural network is used for the recognition segment of the system. The main constraints of the system is with regard to the characteristics of the images being processed. The system should be able to carry out effective recognition of the human faces irrespective of the individual's facial-expression, presence of extraneous objects such as head-gear or spectacles, and face/head orientation. A potential application of this face recognition system would be as a secondary verification method in an automated teller machine.

Leukemia inhibitory factor (LIF) enhances MAP2 + and HUC/D + neurons and influences neurite extension during differentiation of neural progenitors derived from human embryonic stem cells.

EPA Science Inventory

Leukemia Inhibitory Factor (L1F), a member of the Interleukin 6 cytokine family, has a role in differentiation of Human Neural Progenitor (hNP) cells in vitro. hNP cells, derived from Human Embryonic Stem (hES) cells, have an unlimited capacity for self-renewal in monolayer cultu...

The Neural-fuzzy Thermal Error Compensation Controller on CNC Machining Center

NASA Astrophysics Data System (ADS)

Tseng, Pai-Chung; Chen, Shen-Len

The geometric errors and structural thermal deformation are factors that influence the machining accuracy of Computer Numerical Control (CNC) machining center. Therefore, researchers pay attention to thermal error compensation technologies on CNC machine tools. Some real-time error compensation techniques have been successfully demonstrated in both laboratories and industrial sites. The compensation results still need to be enhanced. In this research, the neural-fuzzy theory has been conducted to derive a thermal prediction model. An IC-type thermometer has been used to detect the heat sources temperature variation. The thermal drifts are online measured by a touch-triggered probe with a standard bar. A thermal prediction model is then derived by neural-fuzzy theory based on the temperature variation and the thermal drifts. A Graphic User Interface (GUI) system is also built to conduct the user friendly operation interface with Insprise C++ Builder. The experimental results show that the thermal prediction model developed by neural-fuzzy theory methodology can improve machining accuracy from 80µm to 3µm. Comparison with the multi-variable linear regression analysis the compensation accuracy is increased from ±10µm to ±3µm.

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

PubMed

Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios

2015-06-17

Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

Quantitative proteomics analysis highlights the role of redox hemostasis and energy metabolism in human embryonic stem cell differentiation to neural cells.

PubMed

Fathi, Ali; Hatami, Maryam; Vakilian, Haghighat; Han, Chia-Li; Chen, Yu-Ju; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

2014-04-14

Neural differentiation of human embryonic stem cells (hESCs) is a unique opportunity for in vitro analyses of neurogenesis in humans. Extrinsic cues through neural plate formation are well described in the hESCs although intracellular mechanisms underlying neural development are largely unknown. Proteome analysis of hESC differentiation to neural cells will help to further define molecular mechanisms involved in neurogenesis in humans. Using a two-dimensional differential gel electrophoresis (2D-DIGE) system, we analyzed the proteome of hESC differentiation to neurons at three stages, early neural differentiation, neural ectoderm and mature neurons. Out of 137 differentially accumulated protein spots, 118 spots were identified using MALDI-TOF/TOF and LC MS/MS. We observed that proteins involved in redox hemostasis, vitamin and energy metabolism and ubiquitin dependent proteolysis were more abundant in differentiated cells, whereas the abundance of proteins associated with RNA processing and protein folding was higher in hESCs. Higher abundance of proteins involved in maintaining cellular redox state suggests the importance of redox hemostasis in neural differentiation. Furthermore, our results support the concept of a coupling mechanism between neuronal activity and glucose utilization. The protein network analysis showed that the majority of the interacting proteins were associated with the cell cycle and cellular proliferation. These results enhanced our understanding of the molecular dynamics that underlie neural commitment and differentiation. In highlighting the role of redox and unique metabolic properties of neuronal cells, the present findings add insight to our understanding of hESC differentiation to neurons. The abundance of fourteen proteins involved in maintaining cellular redox state, including 10 members of peroxiredoxin (Prdx) family, mainly increased during differentiation, thus highlighting a link of neural differentiation to redox. Our results revealed markedly higher expression of genes encoding enzymes involved in the glycolysis and amino acid synthesis during differentiation. Protein network analysis predicted a number of critical mediators in hESC differentiation. These proteins included TP53, CTNNB1, SMARCA4, TNF, TERT, E2F1, MYC, RB1, and AR. Copyright © 2014 Elsevier B.V. All rights reserved.

Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in Machado-Joseph disease mice.

PubMed

Mendonça, Liliana S; Nóbrega, Clévio; Hirai, Hirokazu; Kaspar, Brian K; Pereira de Almeida, Luís

2015-02-01

Machado-Joseph disease is a neurodegenerative disease without effective treatment. Patients with Machado-Joseph disease exhibit significant motor impairments such as gait ataxia, associated with multiple neuropathological changes including mutant ATXN3 inclusions, marked neuronal loss and atrophy of the cerebellum. Thus, an effective treatment of symptomatic patients with Machado-Joseph disease may require cell replacement, which we investigated in this study. For this purpose, we injected cerebellar neural stem cells into the cerebellum of adult Machado-Joseph disease transgenic mice and assessed the effect on the neuropathology, neuroinflammation mediators and neurotrophic factor levels and motor coordination. We found that upon transplantation into the cerebellum of adult Machado-Joseph disease mice, cerebellar neural stem cells differentiate into neurons, astrocytes and oligodendrocytes. Importantly, cerebellar neural stem cell transplantation mediated a significant and robust alleviation of the motor behaviour impairments, which correlated with preservation from Machado-Joseph disease-associated neuropathology, namely reduction of Purkinje cell loss, reduction of cellular layer shrinkage and mutant ATXN3 aggregates. Additionally, a significant reduction of neuroinflammation and an increase of neurotrophic factors levels was observed, indicating that transplantation of cerebellar neural stem cells also triggers important neuroprotective effects. Thus, cerebellar neural stem cells have the potential to be used as a cell replacement and neuroprotective approach for Machado-Joseph disease therapy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ca(2+) coding and decoding strategies for the specification of neural and renal precursor cells during development.

PubMed

Moreau, Marc; Néant, Isabelle; Webb, Sarah E; Miller, Andrew L; Riou, Jean-François; Leclerc, Catherine

2016-03-01

During embryogenesis, a rise in intracellular Ca(2+) is known to be a widespread trigger for directing stem cells towards a specific tissue fate, but the precise Ca(2+) signalling mechanisms involved in achieving these pleiotropic effects are still poorly understood. In this review, we compare the Ca(2+) signalling events that appear to be one of the first steps in initiating and regulating both neural determination (neural induction) and kidney development (nephrogenesis). We have highlighted the necessary and sufficient role played by Ca(2+) influx and by Ca(2+) transients in the determination and differentiation of pools of neural or renal precursors. We have identified new Ca(2+) target genes involved in neural induction and we showed that the same Ca(2+) early target genes studied are not restricted to neural tissue but are also present in other tissues, principally in the pronephros. In this review, we also described a mechanism whereby the transcriptional control of gene expression during neurogenesis and nephrogenesis might be directly controlled by Ca(2+) signalling. This mechanism involves members of the Kcnip family such that a change in their binding properties to specific DNA sites is a result of Ca(2+) binding to EF-hand motifs. The different functions of Ca(2+) signalling during these two events illustrate the versatility of Ca(2+) as a second messenger. Copyright © 2015 Elsevier Ltd. All rights reserved.

Examining FKBP5 mRNA expression in human iPSC-derived neural cells

PubMed Central

Lieberman, Richard; Kranzler, Henry R.; Levine, Eric S.; Covault, Jonathan

2016-01-01

In peripheral blood leukocytes, FKBP5 mRNA expression is upregulated following glucocorticoid receptor activation. The single nucleotide polymorphism rs1360780 in FKBP5 is associated with psychiatric illness and has functional molecular effects. However, examination of FKBP5 regulation has largely been limited to peripheral cells, which may not reflect regulation in neural cells. We used 27 human induced pluripotent stem cell lines (iPSCs) derived from 20 subjects to examine FKBP5 mRNA expression following GR activation. Following differentiation into forebrain-lineage neural cultures, cells were exposed to 1μM dexamethasone and mRNA expression of FKBP5 and NR3C1 analyzed. Results from the iPSC-derived neural cells were compared with those from 15 donor matched fibroblast lines. Following dexamethasone treatment, there was a 670% increase in FKBP5 expression in fibroblasts, mimicking findings in peripheral blood-derived cells, but only a 23% increase in iPSC-derived neural cultures. FKBP5 rs1360780 genotype did not affect the induction of FKBP5 mRNA in either fibroblasts or neural cells. These results suggest that iPSC-derived forebrain-lineage neurons may not be an optimal neural cell type in which to examine relationships between GR activation, FKBP5 expression, and genetic variation in human subjects. Further, FKBP5 induction following GR activation may differ between cell types derived from the same individual. PMID:27915167

Coordinated Control of Three-Dimensional Components of Smooth Pursuit to Rotating and Translating Textures.

PubMed

Edinger, Janick; Pai, Dinesh K; Spering, Miriam

2017-01-01

The neural control of pursuit eye movements to visual textures that simultaneously translate and rotate has largely been neglected. Here we propose that pursuit of such targets-texture pursuit-is a fully three-dimensional task that utilizes all three degrees of freedom of the eye, including torsion. Head-fixed healthy human adults (n = 8) tracked a translating and rotating random dot pattern, shown on a computer monitor, with their eyes. Horizontal, vertical, and torsional eye positions were recorded with a head-mounted eye tracker. The torsional component of pursuit is a function of the rotation of the texture, aligned with its visual properties. We observed distinct behaviors between those trials in which stimulus rotation was in the same direction as that of a rolling ball ("natural") in comparison to those with the opposite rotation ("unnatural"): Natural rotation enhanced and unnatural rotation reversed torsional velocity during pursuit, as compared to torsion triggered by a nonrotating random dot pattern. Natural rotation also triggered pursuit with a higher horizontal velocity gain and fewer and smaller corrective saccades. Furthermore, we show that horizontal corrective saccades are synchronized with torsional corrective saccades, indicating temporal coupling of horizontal and torsional saccade control. Pursuit eye movements have a torsional component that depends on the visual stimulus. Horizontal and torsional eye movements are separated in the motor periphery. Our findings suggest that translational and rotational motion signals might be coordinated in descending pursuit pathways.

Distributed Neural Activity Patterns during Human-to-Human Competition

PubMed Central

Piva, Matthew; Zhang, Xian; Noah, J. Adam; Chang, Steve W. C.; Hirsch, Joy

2017-01-01

Interpersonal interaction is the essence of human social behavior. However, conventional neuroimaging techniques have tended to focus on social cognition in single individuals rather than on dyads or groups. As a result, relatively little is understood about the neural events that underlie face-to-face interaction. We resolved some of the technical obstacles inherent in studying interaction using a novel imaging modality and aimed to identify neural mechanisms engaged both within and across brains in an ecologically valid instance of interpersonal competition. Functional near-infrared spectroscopy was utilized to simultaneously measure hemodynamic signals representing neural activity in pairs of subjects playing poker against each other (human–human condition) or against computer opponents (human–computer condition). Previous fMRI findings concerning single subjects confirm that neural areas recruited during social cognition paradigms are individually sensitive to human–human and human–computer conditions. However, it is not known whether face-to-face interactions between opponents can extend these findings. We hypothesize distributed effects due to live processing and specific variations in across-brain coherence not observable in single-subject paradigms. Angular gyrus (AG), a component of the temporal-parietal junction (TPJ) previously found to be sensitive to socially relevant cues, was selected as a seed to measure within-brain functional connectivity. Increased connectivity was confirmed between AG and bilateral dorsolateral prefrontal cortex (dlPFC) as well as a complex including the left subcentral area (SCA) and somatosensory cortex (SS) during interaction with a human opponent. These distributed findings were supported by contrast measures that indicated increased activity at the left dlPFC and frontopolar area that partially overlapped with the region showing increased functional connectivity with AG. Across-brain analyses of neural coherence between the players revealed synchrony between dlPFC and supramarginal gyrus (SMG) and SS in addition to synchrony between AG and the fusiform gyrus (FG) and SMG. These findings present the first evidence of a frontal-parietal neural complex including the TPJ, dlPFC, SCA, SS, and FG that is more active during human-to-human social cognition both within brains (functional connectivity) and across brains (across-brain coherence), supporting a model of functional integration of socially and strategically relevant information during live face-to-face competitive behaviors. PMID:29218005

Heterogeneity in the Segmental Development of the Aortic Tree: Impact on Management of Genetically Triggered Aortic Aneurysms

PubMed Central

Sherif, Hisham M.F.

2014-01-01

An extensive search of the medical literature examining the development of the thoracic aortic tree reveals that the thoracic aorta does not develop as one unit or in one stage: the oldest part of the thoracic aorta is the descending aorta with the aortic arch being the second oldest, developing under influence from the neural crest cell. Following in chronological order are the proximal ascending aorta and aortic root, which develop from a conotruncal origin. Different areas of the thoracic aorta develop under the influence of different gene sets. These parts develop from different cell lineages: the aortic root (the conotruncus), developing from the mesoderm; the ascending aorta and aortic arch, developing from the neural crest cells; and the descending aorta from the mesoderm. Findings illustrate that the thoracic aorta is not a single entity, in developmental terms. It develops from three or four distinct areas, at different stages of embryonic life, and under different sets of genes and signaling pathways. Genetically triggered thoracic aortic aneurysms are not a monolithic group but rather share a multi-genetic origin. Identification of therapeutic targets should be based on the predilection of certain genes to cause aneurysmal disease in specific aortic segments. PMID:26798739

Social contexts modulate neural responses in the processing of others' pain: An event-related potential study.

PubMed

Cui, Fang; Zhu, Xiangru; Luo, Yuejia

2017-08-01

Two hypotheses have been proposed regarding the response that is triggered by observing others' pain: the "empathizing hypothesis" and the "threat value of pain hypothesis." The former suggests that observing others' pain triggers an empathic response. The latter suggests that it activates the threat-detection system. In the present study, participants were instructed to observe pictures that showed an anonymous hand or foot in a painful or non-painful situation in a threatening or friendly social context. Event-related potentials were recorded when the participants passively observed these pictures in different contexts. We observed an interaction between context and picture in the early automatic N1 component, in which the painful pictures elicited a larger amplitude than the non-painful pictures only in the threatening context and not in the friendly context. We also observed an interaction between context and picture in the late P3 component, in which the painful pictures elicited a larger amplitude than the non-painful pictures only in the friendly context and not in the threatening context. These results indicate that specific social contexts can modulate the neural responses to observing others' pain. The "empathic hypothesis" and "threat value of pain hypothesis" are not mutually exclusive and do not contradict each other but rather work in different temporal stages.

Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity.

PubMed

Pereira, Nigel; Elias, Rony T; Neri, Queenie V; Gerber, Rachel S; Lekovich, Jovana P; Palermo, Gianpiero D; Rosenwaks, Zev

2016-11-01

This study investigates whether an adjuvant gonadotrophin-releasing hormone agonist (GnRHa) trigger with human chorionic gonadotrophin (HCG) improves fresh intracytoplasmic sperm injection (ICSI) cycle outcomes in patients with poor fertilization history after standard HCG trigger alone. This study compared 156 patients with <40% fertilization rate in a prior ICSI cycle with standard HCG trigger who underwent another ICSI cycle with a combined 2 mg GnRHa and 1500 IU HCG ovulatory trigger. There was no difference in the baseline demographics, ovarian stimulation outcomes or sperm parameters of the groups. More mature oocytes were retrieved in the combined trigger group compared with the HCG trigger group: 12 (9-14) versus 10 (7-12); P = 0.01. The fertilization rate in the combined trigger group (59.2%) was higher than the HCG group (35.3%); P = 0.01. The odds of clinical pregnancy and live birth were 1.8 and 1.7 times higher, respectively, when comparing the former group to the latter; P = 0.03. The results suggest that combined GnRHa and HCG trigger in ICSI cycles is a reasonable approach to increase oocyte maturity, specifically ooplasmic maturity, thereby increasing fertilization and improving ICSI cycle outcomes in patients with a history of poor fertilization after standard HCG trigger alone. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Within- and across-trial dynamics of human EEG reveal cooperative interplay between reinforcement learning and working memory.

PubMed

Collins, Anne G E; Frank, Michael J

2018-03-06

Learning from rewards and punishments is essential to survival and facilitates flexible human behavior. It is widely appreciated that multiple cognitive and reinforcement learning systems contribute to decision-making, but the nature of their interactions is elusive. Here, we leverage methods for extracting trial-by-trial indices of reinforcement learning (RL) and working memory (WM) in human electro-encephalography to reveal single-trial computations beyond that afforded by behavior alone. Neural dynamics confirmed that increases in neural expectation were predictive of reduced neural surprise in the following feedback period, supporting central tenets of RL models. Within- and cross-trial dynamics revealed a cooperative interplay between systems for learning, in which WM contributes expectations to guide RL, despite competition between systems during choice. Together, these results provide a deeper understanding of how multiple neural systems interact for learning and decision-making and facilitate analysis of their disruption in clinical populations.

Mammalian brain development and our grandmothering life history.

PubMed

Hawkes, Kristen; Finlay, Barbara L

2018-05-02

Among mammals, including humans, adult brain size and the relative size of brain components depend precisely on the duration of a highly regular process of neural development. Much wider variation is seen in rates of body growth and the state of neural maturation at life history events like birth and weaning. Large brains result from slow maturation, which in humans is accompanied by weaning early with respect to both neural maturation and longevity. The grandmother hypothesis proposes this distinctive combination of life history features evolved as ancestral populations began to depend on foods that just weaned juveniles couldn't handle. Here we trace possible reciprocal connections between brain development and life history, highlighting the resulting extended neural plasticity in a wider cognitive ecology of allomaternal care that distinguishes human ontogeny with consequences for other peculiarities of our lineage. Copyright © 2018 Elsevier Inc. All rights reserved.

A neural circuit encoding sexual preference in humans

PubMed Central

Poeppl, Timm B.; Langguth, Berthold; Rupprecht, Rainer; Laird, Angela R; Eickhoff, Simon B.

2016-01-01

Sexual preference determines mate choice for reproduction and hence guarantees conservation of species in mammals. Despite this fundamental role in human behavior, current knowledge on its target-specific neurofunctional substrate is based on lesion studies and therefore limited. We used meta-analytic remodeling of neuroimaging data from 364 human subjects with diverse sexual interests during sexual stimulation to quantify neural regions associated with sexual preference manipulations. We found that sexual preference is encoded by four phylogenetically old, subcortical brain structures. More specifically, sexual preference is controlled by the anterior and preoptic area of the hypothalamus, the anterior and mediodorsal thalamus, the septal area, and the perirhinal parahippocampus including the dentate gyrus. In contrast, sexual non-preference is regulated by the substantia innominata. We anticipate the identification of a core neural circuit for sexual preferences to be a starting point for further sophisticated investigations into the neural principles of sexual behavior and particularly of its aberrations. PMID:27339689

Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development.

PubMed

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L; Baserga, Susan; Yelick, Pamela C

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome.

Separate neural substrates in the human cerebellum for sensory-motor adaptation of reactive and of scanning voluntary saccades.

PubMed

Alahyane, N; Fonteille, V; Urquizar, C; Salemme, R; Nighoghossian, N; Pelisson, D; Tilikete, C

2008-01-01

Sensory-motor adaptation processes are critically involved in maintaining accurate motor behavior throughout life. Yet their underlying neural substrates and task-dependency bases are still poorly understood. We address these issues here by studying adaptation of saccadic eye movements, a well-established model of sensory-motor plasticity. The cerebellum plays a major role in saccadic adaptation but it has not yet been investigated whether this role can account for the known specificity of adaptation to the saccade type (e.g., reactive versus voluntary). Two patients with focal lesions in different parts of the cerebellum were tested using the double-step target paradigm. Each patient was submitted to two separate sessions: one for reactive saccades (RS) triggered by the sudden appearance of a visual target and the second for scanning voluntary saccades (SVS) performed when exploring a more complex scene. We found that a medial cerebellar lesion impaired adaptation of reactive-but not of voluntary-saccades, whereas a lateral lesion affected adaptation of scanning voluntary saccades, but not of reactive saccades. These findings provide the first evidence of an involvement of the lateral cerebellum in saccadic adaptation, and extend the demonstrated role of the cerebellum in RS adaptation to adaptation of SVS. The double dissociation of adaptive abilities is also consistent with our previous hypothesis of the involvement in saccadic adaptation of partially separated cerebellar areas specific to the reactive or voluntary task (Alahyane et al. Brain Res 1135:107-121 (2007)).

Human mesostriatal response tracks motivational tendencies under naturalistic goal conflict.

PubMed

Gonen, Tal; Soreq, Eyal; Eldar, Eran; Ben-Simon, Eti; Raz, Gal; Hendler, Talma

2016-06-01

Goal conflict situations, involving the simultaneous presence of reward and punishment, occur commonly in real life, and reflect well-known individual differences in the behavioral tendency to approach or avoid. However, despite accumulating neural depiction of motivational processing, the investigation of naturalistic approach behavior and its interplay with individual tendencies is remarkably lacking. We developed a novel ecological interactive scenario which triggers motivational behavior under high or low goal conflict conditions. Fifty-five healthy subjects played the game during a functional magnetic resonance imaging scan. A machine-learning approach was applied to classify approach/avoidance behaviors during the game. To achieve an independent measure of individual tendencies, an integrative profile was composed from three established theoretical models. Results demonstrated that approach under high relative to low conflict involved increased activity in the ventral tegmental area (VTA), peri-aquaductal gray, ventral striatum (VS) and precuneus. Notably, only VS and VTA activations during high conflict discriminated between approach/avoidance personality profiles, suggesting that the relationship between individual personality and naturalistic motivational tendencies is uniquely associated with the mesostriatal pathway. VTA-VS further demonstrated stronger coupling during high vs low conflict. These findings are the first to unravel the multilevel relationship among personality profile, approach tendencies in naturalistic set-up and their underlying neural manifestation, thus enabling new avenues for investigating approach-related psychopathologies. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Automatized smoking-related action schemata are reflected by reduced fMRI activity in sensorimotor brain regions of smokers.

PubMed

Isik, Ayse Ilkay; Naumer, Marcus J; Kaiser, Jochen; Buschenlange, Christian; Wiesmann, Sandro; Czoschke, Stefan; Yalachkov, Yavor

2017-01-01

In the later stages of addiction, automatized processes play a prominent role in guiding drug-seeking and drug-taking behavior. However, little is known about the neural correlates of automatized drug-taking skills and drug-related action knowledge in humans. We employed functional magnetic resonance imaging (fMRI) while smokers and non-smokers performed an orientation affordance task, where compatibility between the hand used for a behavioral response and the spatial orientation of a priming stimulus leads to shorter reaction times resulting from activation of the corresponding motor representations. While non-smokers exhibited this behavioral effect only for control objects, smokers showed the affordance effect for both control and smoking-related objects. Furthermore, smokers exhibited reduced fMRI activation for smoking-related as compared to control objects for compatible stimulus-response pairings in a sensorimotor brain network consisting of the right primary motor cortex, supplementary motor area, middle occipital gyrus, left fusiform gyrus and bilateral cingulate gyrus. In the incompatible condition, we found higher fMRI activation in smokers for smoking-related as compared to control objects in the right primary motor cortex, cingulate gyrus, and left fusiform gyrus. This suggests that the activation and performance of deeply embedded, automatized drug-taking schemata employ less brain resources. This might reduce the threshold for relapsing in individuals trying to abstain from smoking. In contrast, the interruption or modification of already triggered automatized action representations require increased neural resources.

Hierarchical graphical-based human pose estimation via local multi-resolution convolutional neural network

NASA Astrophysics Data System (ADS)

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.

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

NASA Astrophysics Data System (ADS)

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].

Neural Basis of Intrinsic Motivation: Evidence from Event-Related Potentials.

PubMed

Jin, Jia; Yu, Liping; Ma, Qingguo

2015-01-01

Human intrinsic motivation is of great importance in human behavior. However, although researchers have focused on this topic for decades, its neural basis was still unclear. The current study employed event-related potentials to investigate the neural disparity between an interesting stop-watch (SW) task and a boring watch-stop task (WS) to understand the neural mechanisms of intrinsic motivation. Our data showed that, in the cue priming stage, the cue of the SW task elicited smaller N2 amplitude than that of the WS task. Furthermore, in the outcome feedback stage, the outcome of the SW task induced smaller FRN amplitude and larger P300 amplitude than that of the WS task. These results suggested that human intrinsic motivation did exist and that it can be detected at the neural level. Furthermore, intrinsic motivation could be quantitatively indexed by the amplitude of ERP components, such as N2, FRN, and P300, in the cue priming stage or feedback stage. Quantitative measurements would also be convenient for intrinsic motivation to be added as a candidate social factor in the construction of a machine learning model.

Infant VEPs reveal neural correlates of implicit naming: Lateralized differences between lexicalized versus name-unknown pictures.

PubMed

Styles, Suzy J; Plunkett, Kim; Duta, Mihaela D

2015-10-01

Recent behavioural studies with toddlers have demonstrated that simply viewing a picture in silence triggers a cascade of linguistic processing which activates a representation of the picture's name (Mani and Plunkett, 2010, 2011). Electrophysiological studies have also shown that viewing a picture modulates the auditory evoked potentials (AEPs) triggered by later speech, from early in the second year of life (Duta et al., 2012; Friedrich and Friederici, 2005; Mani et al., 2011) further supporting the notion that picture viewing gives rise to a representation of the picture's name against which later speech can be matched. However, little is known about how and when the implicit name arises during picture viewing, or about the electrophysiological activity which supports this linguistic process. We report differences in the visual evoked potentials (VEPs) of fourteen-month-old infants who saw photographs of animals and objects, some of which were name-known (lexicalized), while waiting for an auditory label to be presented. During silent picture viewing, lateralized neural activity was selectively triggered by lexicalized items, as compared to nameless items. Lexicalized items generated a short-lasting negative-going deflection over frontal, left centro-temporal, and left occipital regions shortly after the picture appeared (126-225 ms). A positive deflection was also observed over the right hemisphere (particularly centro-temporal regions) in a later, longer-lasting window (421-720 ms). The lateralization of these differences in the VEP suggests the possible involvement of linguistic processes during picture viewing, and may reflect activity involved in the implicit activation of the picture's name. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Infant VEPs reveal neural correlates of implicit naming: Lateralized differences between lexicalized versus name-unknown pictures

PubMed Central

Styles, Suzy J.; Plunkett, Kim; Duta, Mihaela D.

2015-01-01

Recent behavioural studies with toddlers have demonstrated that simply viewing a picture in silence triggers a cascade of linguistic processing which activates a representation of the picture’s name (Mani and Plunkett, 2010, 2011). Electrophysiological studies have also shown that viewing a picture modulates the auditory evoked potentials (AEPs) triggered by later speech, from early in the second year of life (Duta et al., 2012; Friedrich and Friederici, 2005; Mani et al., 2011) further supporting the notion that picture viewing gives rise to a representation of the picture’s name against which later speech can be matched. However, little is known about how and when the implicit name arises during picture viewing, or about the electrophysiological activity which supports this linguistic process. We report differences in the visual evoked potentials (VEPs) of fourteen-month-old infants who saw photographs of animals and objects, some of which were name-known (lexicalized), while waiting for an auditory label to be presented. During silent picture viewing, lateralized neural activity was selectively triggered by lexicalized items, as compared to nameless items. Lexicalized items generated a short-lasting negative-going deflection over frontal, left centro-temporal, and left occipital regions shortly after the picture appeared (126–225 ms). A positive deflection was also observed over the right hemisphere (particularly centro-temporal regions) in a later, longer-lasting window (421–720 ms). The lateralization of these differences in the VEP suggests the possible involvement of linguistic processes during picture viewing, and may reflect activity involved in the implicit activation of the picture’s name. PMID:26232744

Signaling through three chemokine receptors triggers the migration of transplanted neural precursor cells in a model of multiple sclerosis.

PubMed

Cohen, Mikhal E; Fainstein, Nina; Lavon, Iris; Ben-Hur, Tamir

2014-09-01

Multiple sclerosis (MS) is a multifocal disease, and precursor cells need to migrate into the multiple lesions in order to exert their therapeutic effects. Therefore, cell migration is a crucial element in regenerative processes in MS, dictating the route of delivery, when cell transplantation is considered. We have previously shown that inflammation triggers migration of multi-potential neural precursor cells (NPCs) into the white matter of experimental autoimmune encephalomyelitis (EAE) rodents, a widely used model of MS. Here we investigated the molecular basis of this attraction. NPCs were grown from E13 embryonic mouse brains and transplanted into the lateral cerebral ventricles of EAE mice. Transplanted NPC migration was directed by three tissue-derived chemokines. Stromal cell-derived factor-1α, monocyte chemo-attractant protein-1 and hepatocyte growth factor were expressed in the EAE brain and specifically in microglia and astrocytes. Their cognate receptors, CXCR4, CCR2 or c-Met were constitutively expressed on NPCs. Selective blockage of CXCR4, CCR2 or c-Met partially inhibited NPC migration in EAE brains. Blocking all three receptors had an additive effect and resulted in profound inhibition of NPC migration, as compared to extensive migration of control NPCs. The inflammation-triggered NPC migration into white matter tracts was dependent on a motile NPC phenotype. Specifically, depriving NPCs from epidermal growth factor (EGF) prevented the induction of glial commitment and a motile phenotype (as indicated by an in vitro motility assay), hampering their response to neuroinflammation. In conclusion, signaling via three chemokine systems accounts for most of the inflammation-induced, tissue-derived attraction of transplanted NPCs into white matter tracts during EAE. Copyright © 2014. Published by Elsevier B.V.

Study of t$$\\bar{t}$$ production in tau jets channel at CDFII using neural networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amerio, Silvia

CDF (Collider Detector at Fermilab) is a particle detector located at Fermi National Laboratories, near Chicago. it allows to study decay products of pmore » $$\\bar{p}$$ collisions at center-of-mass energy of 1.96 TeV. During its first period of data taking (RunI), CDF observed for the first time the top quark (1995). The current period of data taking (RunII) is devoted to precise measurements of top properties and to search for new physics. This thesis work is about the top decay channel named τ + jets. A t$$\\bar{t}$$ pair decays in two W bosons and two b quarks. In a τ + jets event, one out of the two W decays into two jets of hadrons, while the other produces a τ lepton and a neutrino; the τ decays semileptonically in one or more charged and neutral pions while b quarks hadronize producing two jets of particles. Thus the final state of a τ + jets event has this specific signature: five jets, one τ-like, i.e. narrow and with low track multiplicity, two from b quarks, two from a W boson and a large amount of missing energy from two τ neutrinos. They search for this signal in 311 pb -1 of data collected with TOP{_}MULTIJET trigger. They use neural networks to separate signal from background and on the selected sample they perform a t$$\\bar{t}$$ production cross section measurement. The thesis is structured as follows: in Chapter 1 they outline the physics of top and τ, concentrating on their discovery, production mechanisms and current physics results involving them. Chapter 2 is devoted to the description of the experimental setup: the accelerator complex first and CDF detector then. The trigger system is described in Chapter 3, while Chapter 4 shows how particles are reconstructed exploiting information from different CDF subdetectors. With Chapter 5 they begin to present their analysis: we use a feed forward neural network based on a minimization algorithm developed in Trento University, called Reactive Taboo Search (RTS), especially designed to rapidly escape from local minima. Using this neural network, they explore two techniques to select t$$\\bar{t}$$ → τ + jets events, the first based on a single net, the second on two neural networks in cascade; both techniques are described in Chapter 6, together with the variables used as inputs for the nets. Finally, in Chapter 7 they present a method to measure cross section on the sample of events selected by neural networks.« less

Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking.

PubMed

Augur, Isabel F; Wyckoff, Andrew R; Aston-Jones, Gary; Kalivas, Peter W; Peters, Jamie

2016-09-28

The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself. We used a retro-DREADD approach to confine the Gq-DREADD to vmPFC neurons that project to the medial nucleus accumbens shell, confirming that these neurons are responsible for the decreased cue-induced reinstatement of cocaine seeking. The effects of vmPFC activation on cue-induced reinstatement depended on prior extinction training, consistent with the reported role of this structure in extinction memory. These data help define the conditions under which chemogenetic activation of extinction neural circuits can be exploited to reduce relapse triggered by reminder cues. The ventromedial prefrontal cortex (vmPFC) projection to the nucleus accumbens shell is important for extinction of cocaine seeking, but its anatomical proximity to the relapse-promoting projection from the dorsomedial prefrontal cortex to the nucleus accumbens core makes it difficult to selectively enhance neuronal activity in one pathway or the other using traditional pharmacotherapy (e.g., systemically administered drugs). Viral-mediated gene delivery of an activating Gq-DREADD to vmPFC and/or vmPFC projections to the nucleus accumbens shell allows the chemogenetic exploitation of this extinction neural circuit to reduce cocaine seeking and was particularly effective against relapse triggered by cocaine reminder cues. Copyright © 2016 the authors 0270-6474/16/3610174-07$15.00/0.

Analysis of the effects of geological and geomorphological factors on earthquake triggered landslides using artificial neural networks (ANN)

NASA Astrophysics Data System (ADS)

Kawabata, D.; Bandibas, J.

2007-12-01

The occurrence of landslide is the result of the interaction of complex and diverse environmental factors. The geomorphic and geologic features, rock types and vegetative cover are important base factors of landslide occurrence. However, determining the relationship between these factors and landslide occurrence is very difficult using conventional mathematical analysis. The use of an advanced computing technique for this kind of analysis is very important. Artificial neural network (ANN) has recently been included in the list of analytical tools for a wide range of applications in the natural sciences research fields. One of the advantages of using ANN for pattern recognition is that it can handle data at any measurement scale ranging from nominal, ordinal to linear and ratio, and any form of data distribution (Wang et al., 1995). In addition, it can easily handle qualitative variables making it widely used in integrated analysis of spatial data from multiple sources for predicting and classification. This study focuses on the definition of the relationship between geological factors and landslide occurrence using artificial neural networks. The study also focuses on the effect of the DTMs (e.g. ASTER DTM, ALSM, digitized from paper map and digital photogrammetric measurement data). The main aim of the study is to generate landslide susceptibility index map using the defined relationship using ANN. Landslide data in the Chuetsu region were used in this research. The 2004 earthquake triggered many landslides in the region. The initial results of the study showed that ANN is more accurate in defining the relationship between geological and geomorphological factors and landslide occurrence. It also determined the best combination of geological and geomorphological factors that is directly related to landslide occurrence.

The Magnitude of Trial-By-Trial Neural Variability Is Reproducible over Time and across Tasks in Humans.

PubMed

Arazi, Ayelet; Gonen-Yaacovi, Gil; Dinstein, Ilan

2017-01-01

Numerous studies have shown that neural activity in sensory cortices is remarkably variable over time and across trials even when subjects are presented with an identical repeating stimulus or task. This trial-by-trial neural variability is relatively large in the prestimulus period and considerably smaller (quenched) following stimulus presentation. Previous studies have suggested that the magnitude of neural variability affects behavior such that perceptual performance is better on trials and in individuals where variability quenching is larger. To what degree are neural variability magnitudes of individual subjects flexible or static? Here, we used EEG recordings from adult humans to demonstrate that neural variability magnitudes in visual cortex are remarkably consistent across different tasks and recording sessions. While magnitudes of neural variability differed dramatically across individual subjects, they were surprisingly stable across four tasks with different stimuli, temporal structures, and attentional/cognitive demands as well as across experimental sessions separated by one year. These experiments reveal that, in adults, neural variability magnitudes are mostly solidified individual characteristics that change little with task or time, and are likely to predispose individual subjects to exhibit distinct behavioral capabilities.

Amygdala Lesions Reduce Cataplexy in Orexin KO mice

PubMed Central

Burgess, C.R.; Oishi, Y.; Mochizuki, T.; Peever, J.H.; Scammell, T.E.

2013-01-01

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of REM sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal grey, lateral pontine tegmentum, locus coeruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knockout mice, a model of narcolepsy. These lesions did not alter basic sleep/wake behavior, but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia. PMID:23739970

Amygdala lesions reduce cataplexy in orexin knock-out mice.

PubMed

Burgess, Christian R; Oishi, Yo; Mochizuki, Takatoshi; Peever, John H; Scammell, Thomas E

2013-06-05

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of rapid eye movement sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal gray, lateral pontine tegmentum, locus ceruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knock-out mice, a model of narcolepsy. These lesions did not alter basic sleep-wake behavior but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia.

Gender development and the human brain.

PubMed

Hines, Melissa

2011-01-01

Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

Application of structured support vector machine backpropagation to a convolutional neural network for human pose estimation.

PubMed

Witoonchart, Peerajak; Chongstitvatana, Prabhas

2017-08-01

In this study, for the first time, we show how to formulate a structured support vector machine (SSVM) as two layers in a convolutional neural network, where the top layer is a loss augmented inference layer and the bottom layer is the normal convolutional layer. We show that a deformable part model can be learned with the proposed structured SVM neural network by backpropagating the error of the deformable part model to the convolutional neural network. The forward propagation calculates the loss augmented inference and the backpropagation calculates the gradient from the loss augmented inference layer to the convolutional layer. Thus, we obtain a new type of convolutional neural network called an Structured SVM convolutional neural network, which we applied to the human pose estimation problem. This new neural network can be used as the final layers in deep learning. Our method jointly learns the structural model parameters and the appearance model parameters. We implemented our method as a new layer in the existing Caffe library. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Finding the beat: a neural perspective across humans and non-human primates.

PubMed

Merchant, Hugo; Grahn, Jessica; Trainor, Laurel; Rohrmeier, Martin; Fitch, W Tecumseh

2015-03-19

Humans possess an ability to perceive and synchronize movements to the beat in music ('beat perception and synchronization'), and recent neuroscientific data have offered new insights into this beat-finding capacity at multiple neural levels. Here, we review and compare behavioural and neural data on temporal and sequential processing during beat perception and entrainment tasks in macaques (including direct neural recording and local field potential (LFP)) and humans (including fMRI, EEG and MEG). These abilities rest upon a distributed set of circuits that include the motor cortico-basal-ganglia-thalamo-cortical (mCBGT) circuit, where the supplementary motor cortex (SMA) and the putamen are critical cortical and subcortical nodes, respectively. In addition, a cortical loop between motor and auditory areas, connected through delta and beta oscillatory activity, is deeply involved in these behaviours, with motor regions providing the predictive timing needed for the perception of, and entrainment to, musical rhythms. The neural discharge rate and the LFP oscillatory activity in the gamma- and beta-bands in the putamen and SMA of monkeys are tuned to the duration of intervals produced during a beat synchronization-continuation task (SCT). Hence, the tempo during beat synchronization is represented by different interval-tuned cells that are activated depending on the produced interval. In addition, cells in these areas are tuned to the serial-order elements of the SCT. Thus, the underpinnings of beat synchronization are intrinsically linked to the dynamics of cell populations tuned for duration and serial order throughout the mCBGT. We suggest that a cross-species comparison of behaviours and the neural circuits supporting them sets the stage for a new generation of neurally grounded computational models for beat perception and synchronization. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Finding the beat: a neural perspective across humans and non-human primates

PubMed Central

Merchant, Hugo; Grahn, Jessica; Trainor, Laurel; Rohrmeier, Martin; Fitch, W. Tecumseh

2015-01-01

Humans possess an ability to perceive and synchronize movements to the beat in music (‘beat perception and synchronization’), and recent neuroscientific data have offered new insights into this beat-finding capacity at multiple neural levels. Here, we review and compare behavioural and neural data on temporal and sequential processing during beat perception and entrainment tasks in macaques (including direct neural recording and local field potential (LFP)) and humans (including fMRI, EEG and MEG). These abilities rest upon a distributed set of circuits that include the motor cortico-basal-ganglia–thalamo-cortical (mCBGT) circuit, where the supplementary motor cortex (SMA) and the putamen are critical cortical and subcortical nodes, respectively. In addition, a cortical loop between motor and auditory areas, connected through delta and beta oscillatory activity, is deeply involved in these behaviours, with motor regions providing the predictive timing needed for the perception of, and entrainment to, musical rhythms. The neural discharge rate and the LFP oscillatory activity in the gamma- and beta-bands in the putamen and SMA of monkeys are tuned to the duration of intervals produced during a beat synchronization–continuation task (SCT). Hence, the tempo during beat synchronization is represented by different interval-tuned cells that are activated depending on the produced interval. In addition, cells in these areas are tuned to the serial-order elements of the SCT. Thus, the underpinnings of beat synchronization are intrinsically linked to the dynamics of cell populations tuned for duration and serial order throughout the mCBGT. We suggest that a cross-species comparison of behaviours and the neural circuits supporting them sets the stage for a new generation of neurally grounded computational models for beat perception and synchronization. PMID:25646516

Neural-network-directed alignment of optical systems using the laser-beam spatial filter as an example

NASA Technical Reports Server (NTRS)

Decker, Arthur J.; Krasowski, Michael J.; Weiland, Kenneth E.

1993-01-01

This report describes an effort at NASA Lewis Research Center to use artificial neural networks to automate the alignment and control of optical measurement systems. Specifically, it addresses the use of commercially available neural network software and hardware to direct alignments of the common laser-beam-smoothing spatial filter. The report presents a general approach for designing alignment records and combining these into training sets to teach optical alignment functions to neural networks and discusses the use of these training sets to train several types of neural networks. Neural network configurations used include the adaptive resonance network, the back-propagation-trained network, and the counter-propagation network. This work shows that neural networks can be used to produce robust sequencers. These sequencers can learn by example to execute the step-by-step procedures of optical alignment and also can learn adaptively to correct for environmentally induced misalignment. The long-range objective is to use neural networks to automate the alignment and operation of optical measurement systems in remote, harsh, or dangerous aerospace environments. This work also shows that when neural networks are trained by a human operator, training sets should be recorded, training should be executed, and testing should be done in a manner that does not depend on intellectual judgments of the human operator.

Post interaural neural net-based vowel recognition

NASA Astrophysics Data System (ADS)

Jouny, Ismail I.

2001-10-01

Interaural head related transfer functions are used to process speech signatures prior to neural net based recognition. Data representing the head related transfer function of a dummy has been collected at MIT and made available on the Internet. This data is used to pre-process vowel signatures to mimic the effects of human ear on speech perception. Signatures representing various vowels of the English language are then presented to a multi-layer perceptron trained using the back propagation algorithm for recognition purposes. The focus in this paper is to assess the effects of human interaural system on vowel recognition performance particularly when using a classification system that mimics the human brain such as a neural net.

Tutorial: Neural networks and their potential application in nuclear power plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uhrig, R.E.

A neural network is a data processing system consisting of a number of simple, highly interconnected processing elements in an architecture inspired by the structure of the cerebral cortex portion of the brain. Hence, neural networks are often capable of doing things which humans or animals do well but which conventional computers often do poorly. Neural networks have emerged in the past few years as an area of unusual opportunity for research, development and application to a variety of real world problems. Indeed, neural networks exhibit characteristics and capabilities not provided by any other technology. Examples include reading Japanese Kanjimore » characters and human handwriting, reading a typewritten manuscript aloud, compensating for alignment errors in robots, interpreting very noise'' signals (e.g. electroencephalograms), modeling complex systems that cannot be modelled mathematically, and predicting whether proposed loans will be good or fail. This paper presents a brief tutorial on neural networks and describes research on the potential applications to nuclear power plants.« less

The immune-neuro-endocrine interactions.

PubMed

Tomaszewska, D; Przekop, F

1997-06-01

This article reviews data concerning the interactions between immune, endocrine and neural systems in physiological, pathophysiological and stress conditions in animals and humans. Numerous studies have provided evidence that these systems interact with each other in maintaining homeostasis. This interaction may be classified as follows: immune, endocrine and neural cell products coexist in lymphoid, endocrine and neural tissue. Endocrine and neural mediators modulate immune system activity. Immune, endocrine and neural cells express receptors for cytokines, hormones, neuropeptides and transmitters.

GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures.

PubMed

Lieberman, Richard; Kranzler, Henry R; Joshi, Pujan; Shin, Dong-Guk; Covault, Jonathan

2015-09-01

Genetic variation in a region of chromosome 4p12 that includes the GABAA subunit gene GABRA2 has been reproducibly associated with alcohol dependence (AD). However, the molecular mechanisms underlying the association are unknown. This study examined correlates of in vitro gene expression of the AD-associated GABRA2 rs279858*C-allele in human neural cells using an induced pluripotent stem cell (iPSC) model system. We examined mRNA expression of chromosome 4p12 GABAA subunit genes (GABRG1, GABRA2, GABRA4, and GABRB1) in 36 human neural cell lines differentiated from iPSCs using quantitative polymerase chain reaction and next-generation RNA sequencing. mRNA expression in adult human brain was examined using the BrainCloud and BRAINEAC data sets. We found significantly lower levels of GABRA2 mRNA in neural cell cultures derived from rs279858*C-allele carriers. Levels of GABRA2 RNA were correlated with those of the other 3 chromosome 4p12 GABAA genes, but not other neural genes. Cluster analysis based on the relative RNA levels of the 4 chromosome 4p12 GABAA genes identified 2 distinct clusters of cell lines, a low-expression cluster associated with rs279858*C-allele carriers and a high-expression cluster enriched for the rs279858*T/T genotype. In contrast, there was no association of genotype with chromosome 4p12 GABAA gene expression in postmortem adult cortex in either the BrainCloud or BRAINEAC data sets. AD-associated variation in GABRA2 is associated with differential expression of the entire cluster of GABAA subunit genes on chromosome 4p12 in human iPSC-derived neural cell cultures. The absence of a parallel effect in postmortem human adult brain samples suggests that AD-associated genotype effects on GABAA expression, although not present in mature cortex, could have effects on regulation of the chromosome 4p12 GABAA cluster during neural development. Copyright © 2015 by the Research Society on Alcoholism.

The Effect of Agmatine on Expression of IL-1β and TLX Which Promotes Neuronal Differentiation in Lipopolysaccharide-Treated Neural Progenitors.

PubMed

Song, Juhyun; Kumar, Bokara Kiran; Kang, Somang; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

2013-12-01

Differentiation of neural progenitor cells (NPCs) is important for protecting neural cells and brain tissue during inflammation. Interleukin-1 beta (IL-1β) is the most common pro- inflammatory cytokine in brain inflammation, and increased IL-1β levels can decrease the proliferation of NPCs. We aimed to investigate whether agmatine (Agm), a primary polyamine that protects neural cells, could trigger differentiation of NPCs by activating IL-1β in vitro. The cortex of ICR mouse embryos (E14) was dissociated to culture NPCs. NPCs were stimulated by lipopolysaccharide (LPS). After 6 days, protein expression of stem cell markers and differentiation signal factors was confirmed by using western blot analysis. Also, immunocytochemistry was used to confirm the cell fate. Agm treatment activated NPC differentiation significantly more than in the control group, which was evident by the increased expression of a neuronal marker, MAP2, in the LPS-induced, Agm-treated group. Differentiation of LPS-induced, Agm-treated NPCs was regulated by the MAPK pathway and is thought to be related to IL-1β activation and decreased expression of TLX, a transcription factor that regulates NPC differentiation. Our results reveal that Agm can promote NPC differentiation to neural stem cells by modulating IL-1β expression under inflammatory condition, and they suggest that Agm may be a novel therapeutic strategy for neuroinflammatory diseases.

Updating Procedures Can Reorganize the Neural Circuit Supporting a Fear Memory.

PubMed

Kwapis, Janine L; Jarome, Timothy J; Ferrara, Nicole C; Helmstetter, Fred J

2017-07-01

Established memories undergo a period of vulnerability following retrieval, a process termed 'reconsolidation.' Recent work has shown that the hypothetical process of reconsolidation is only triggered when new information is presented during retrieval, suggesting that this process may allow existing memories to be modified. Reconsolidation has received increasing attention as a possible therapeutic target for treating disorders that stem from traumatic memories, yet little is known about how this process changes the original memory. In particular, it is unknown whether reconsolidation can reorganize the neural circuit supporting an existing memory after that memory is modified with new information. Here, we show that trace fear memory undergoes a protein synthesis-dependent reconsolidation process following exposure to a single updating trial of delay conditioning. Further, this reconsolidation-dependent updating process appears to reorganize the neural circuit supporting the trace-trained memory, so that it better reflects the circuit supporting delay fear. Specifically, after a trace-to-delay update session, the amygdala is now required for extinction of the updated memory but the retrosplenial cortex is no longer required for retrieval. These results suggest that updating procedures could be used to force a complex, poorly defined memory circuit to rely on a better-defined neural circuit that may be more amenable to behavioral or pharmacological manipulation. This is the first evidence that exposure to new information can fundamentally reorganize the neural circuit supporting an existing memory.

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

PubMed

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

2018-01-01

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

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates.

PubMed

Keeney, J G; Davis, J M; Siegenthaler, J; Post, M D; Nielsen, B S; Hopkins, W D; Sikela, J M

2015-09-01

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Neurophysiology and Neuroanatomy of Reflexive and Volitional Saccades: Evidence from Studies of Humans

ERIC Educational Resources Information Center

McDowell, Jennifer E.; Dyckman, Kara A.; Austin, Benjamin P.; Clementz, Brett A.

2008-01-01

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually guided saccades (redirections of gaze to a visual stimulus or pro-saccades) and more complex volitional saccades require similar basic neural circuitry…

FACS-based Isolation of Neural and Glioma Stem Cell Populations from Fresh Human Tissues Utilizing EGF Ligand

PubMed Central

Tome-Garcia, Jessica; Doetsch, Fiona; Tsankova, Nadejda M.

2018-01-01

Direct isolation of human neural and glioma stem cells from fresh tissues permits their biological study without prior culture and may capture novel aspects of their molecular phenotype in their native state. Recently, we demonstrated the ability to prospectively isolate stem cell populations from fresh human germinal matrix and glioblastoma samples, exploiting the ability of cells to bind the Epidermal Growth Factor (EGF) ligand in fluorescence-activated cell sorting (FACS). We demonstrated that FACS-isolated EGF-bound neural and glioblastoma populations encompass the sphere-forming colonies in vitro, and are capable of both self-renewal and multilineage differentiation. Here we describe in detail the purification methodology of EGF-bound (i.e., EGFR+) human neural and glioma cells with stem cell properties from fresh postmortem and surgical tissues. The ability to prospectively isolate stem cell populations using native ligand-binding ability opens new doors for understanding both normal and tumor cell biology in uncultured conditions, and is applicable for various downstream molecular sequencing studies at both population and single-cell resolution. PMID:29516026

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

NASA Technical Reports Server (NTRS)

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 the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.

Morphological inversion of complex diffusion

NASA Astrophysics Data System (ADS)

Nguyen, V. A. T.; Vural, D. C.

2017-09-01

Epidemics, neural cascades, power failures, and many other phenomena can be described by a diffusion process on a network. To identify the causal origins of a spread, it is often necessary to identify the triggering initial node. Here, we define a new morphological operator and use it to detect the origin of a diffusive front, given the final state of a complex network. Our method performs better than algorithms based on distance (closeness) and Jordan centrality. More importantly, our method is applicable regardless of the specifics of the forward model, and therefore can be applied to a wide range of systems such as identifying the patient zero in an epidemic, pinpointing the neuron that triggers a cascade, identifying the original malfunction that causes a catastrophic infrastructure failure, and inferring the ancestral species from which a heterogeneous population evolves.

An internal thermal sensor controlling temperature preference in Drosophila.

PubMed

Hamada, Fumika N; Rosenzweig, Mark; Kang, Kyeongjin; Pulver, Stefan R; Ghezzi, Alfredo; Jegla, Timothy J; Garrity, Paul A

2008-07-10

Animals from flies to humans are able to distinguish subtle gradations in temperature and show strong temperature preferences. Animals move to environments of optimal temperature and some manipulate the temperature of their surroundings, as humans do using clothing and shelter. Despite the ubiquitous influence of environmental temperature on animal behaviour, the neural circuits and strategies through which animals select a preferred temperature remain largely unknown. Here we identify a small set of warmth-activated anterior cell (AC) neurons located in the Drosophila brain, the function of which is critical for preferred temperature selection. AC neuron activation occurs just above the fly's preferred temperature and depends on dTrpA1, an ion channel that functions as a molecular sensor of warmth. Flies that selectively express dTrpA1 in the AC neurons select normal temperatures, whereas flies in which dTrpA1 function is reduced or eliminated choose warmer temperatures. This internal warmth-sensing pathway promotes avoidance of slightly elevated temperatures and acts together with a distinct pathway for cold avoidance to set the fly's preferred temperature. Thus, flies select a preferred temperature by using a thermal sensing pathway tuned to trigger avoidance of temperatures that deviate even slightly from the preferred temperature. This provides a potentially general strategy for robustly selecting a narrow temperature range optimal for survival.

Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

PubMed

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.

Real-time data acquisition and control system for the measurement of motor and neural data

PubMed Central

Bryant, Christopher L.; Gandhi, Neeraj J.

2013-01-01

This paper outlines a powerful, yet flexible real-time data acquisition and control system for use in the triggering and measurement of both analog and digital events. Built using the LabVIEW development architecture (version 7.1) and freely available, this system provides precisely timed auditory and visual stimuli to a subject while recording analog data and timestamps of neural activity retrieved from a window discriminator. The system utilizes the most recent real-time (RT) technology in order to provide not only a guaranteed data acquisition rate of 1 kHz, but a much more difficult to achieve guaranteed system response time of 1 ms. The system interface is windows-based and easy to use, providing a host of configurable options for end-user customization. PMID:15698659

Aminopropyl carbazole analogues as potent enhancers of neurogenesis.

PubMed

Yoon, Hye Jin; Kong, Sun-Young; Park, Min-Hye; Cho, Yongsung; Kim, Sung-Eun; Shin, Jae-Yeon; Jung, Sunghye; Lee, Jiyoun; Farhanullah; Kim, Hyun-Jung; Lee, Jeewoo

2013-11-15

Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

A programmable closed-loop recording and stimulating wireless system for behaving small laboratory animals

PubMed Central

Angotzi, Gian Nicola; Boi, Fabio; Zordan, Stefano; Bonfanti, Andrea; Vato, Alessandro

2014-01-01

A portable 16-channels microcontroller-based wireless system for a bi-directional interaction with the central nervous system is presented in this work. The device is designed to be used with freely behaving small laboratory animals and allows recording of spontaneous and evoked neural activity wirelessly transmitted and stored on a personal computer. Biphasic current stimuli with programmable duration, frequency and amplitude may be triggered in real-time on the basis of the recorded neural activity as well as by the animal behavior within a specifically designed experimental setup. An intuitive graphical user interface was developed to configure and to monitor the whole system. The system was successfully tested through bench tests and in vivo measurements on behaving rats chronically implanted with multi-channels microwire arrays. PMID:25096831

Generating trunk neural crest from human pluripotent stem cells

PubMed Central

Huang, Miller; Miller, Matthew L.; McHenry, Lauren K.; Zheng, Tina; Zhen, Qiqi; Ilkhanizadeh, Shirin; Conklin, Bruce R.; Bronner, Marianne E.; Weiss, William A.

2016-01-01

Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior “cranial” NCC form craniofacial bone, whereas solely posterior “trunk” NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages. PMID:26812940

Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans.

PubMed

Kasum, Miro; Franulić, Daniela; Čehić, Ermin; Orešković, Slavko; Lila, Albert; Ejubović, Emina

2017-08-01

The aim of this review is to analyse the effectiveness of exogenous kisspeptin administration as a novel alternative of triggering oocyte maturation, instead of currently used triggers such as human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist, in women undergoing in vitro fertilisation (IVF) treatment. Kisspeptin has been considered a master regulator of two modes of GnRH and hence gonadotropin secretion, pulses and surges. Administration of kisspeptin-10 and kisspeptin-54 induces the luteinising hormone (LH) surge required for egg maturation and ovulation in animal investigations and LH release during the preovulatory phase of the menstrual cycle and hypothalamic amenorrhoea in humans. Exogenous kisspeptin-54 has been successfully administered as a promising method of triggering oocyte maturation, following ovarian stimulation with gonadotropins and GnRH antagonists in women undergoing IVF, due to its efficacy considering achieved pregnancy rates compared to hCG and GnRH agonists. Also, its safety in patients at high risk of developing ovarian hyperstimulation syndrome is noteworthy. Nevertheless, further studies would be desirable to establish the optimal trigger of egg maturation and to improve the reproductive outcome for women undergoing IVF treatment.

Human activity recognition based on feature selection in smart home using back-propagation algorithm.

PubMed

Fang, Hongqing; He, Lei; Si, Hao; Liu, Peng; Xie, Xiaolei

2014-09-01

In this paper, Back-propagation(BP) algorithm has been used to train the feed forward neural network for human activity recognition in smart home environments, and inter-class distance method for feature selection of observed motion sensor events is discussed and tested. And then, the human activity recognition performances of neural network using BP algorithm have been evaluated and compared with other probabilistic algorithms: Naïve Bayes(NB) classifier and Hidden Markov Model(HMM). The results show that different feature datasets yield different activity recognition accuracy. The selection of unsuitable feature datasets increases the computational complexity and degrades the activity recognition accuracy. Furthermore, neural network using BP algorithm has relatively better human activity recognition performances than NB classifier and HMM. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

The neural bases for valuing social equality.

PubMed

Aoki, Ryuta; Yomogida, Yukihito; Matsumoto, Kenji

2015-01-01

The neural basis of how humans value and pursue social equality has become a major topic in social neuroscience research. Although recent studies have identified a set of brain regions and possible mechanisms that are involved in the neural processing of equality of outcome between individuals, how the human brain processes equality of opportunity remains unknown. In this review article, first we describe the importance of the distinction between equality of outcome and equality of opportunity, which has been emphasized in philosophy and economics. Next, we discuss possible approaches for empirical characterization of human valuation of equality of opportunity vs. equality of outcome. Understanding how these two concepts are distinct and interact with each other may provide a better explanation of complex human behaviors concerning fairness and social equality. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles

PubMed Central

Smith, Alec; Lohrenz, Terry; King, Justin; Montague, P. Read; Camerer, Colin F.

2014-01-01

Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during pathological overvaluations—price bubbles. The connection between the behavioral and neural underpinnings of such phenomena has been absent, in part due to a lack of enabling technology. We used a multisubject functional MRI paradigm to measure neural activity in human subjects participating in experimental asset markets in which endogenous price bubbles formed and crashed. Although many ideas exist about how and why such bubbles may form and how to identify them, our experiment provided a window on the connection between neural responses and behavioral acts (buying and selling) that created the bubbles. We show that aggregate neural activity in the nucleus accumbens (NAcc) tracks the price bubble and that NAcc activity aggregated within a market predicts future price changes and crashes. Furthermore, the lowest-earning subjects express a stronger tendency to buy as a function of measured NAcc activity. Conversely, we report a signal in the anterior insular cortex in the highest earners that precedes the impending price peak, is associated with a higher propensity to sell in high earners, and that may represent a neural early warning signal in these subjects. Such markets could be a model system to understand neural and behavior mechanisms in other settings where emergent group-level activity exhibits mistaken belief or valuation. PMID:25002476

Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles.

PubMed

Smith, Alec; Lohrenz, Terry; King, Justin; Montague, P Read; Camerer, Colin F

2014-07-22

Groups of humans routinely misassign value to complex future events, especially in settings involving the exchange of resources. If properly structured, experimental markets can act as excellent probes of human group-level valuation mechanisms during pathological overvaluations--price bubbles. The connection between the behavioral and neural underpinnings of such phenomena has been absent, in part due to a lack of enabling technology. We used a multisubject functional MRI paradigm to measure neural activity in human subjects participating in experimental asset markets in which endogenous price bubbles formed and crashed. Although many ideas exist about how and why such bubbles may form and how to identify them, our experiment provided a window on the connection between neural responses and behavioral acts (buying and selling) that created the bubbles. We show that aggregate neural activity in the nucleus accumbens (NAcc) tracks the price bubble and that NAcc activity aggregated within a market predicts future price changes and crashes. Furthermore, the lowest-earning subjects express a stronger tendency to buy as a function of measured NAcc activity. Conversely, we report a signal in the anterior insular cortex in the highest earners that precedes the impending price peak, is associated with a higher propensity to sell in high earners, and that may represent a neural early warning signal in these subjects. Such markets could be a model system to understand neural and behavior mechanisms in other settings where emergent group-level activity exhibits mistaken belief or valuation.

Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling.

PubMed

Singec, Ilyas; Crain, Andrew M; Hou, Junjie; Tobe, Brian T D; Talantova, Maria; Winquist, Alicia A; Doctor, Kutbuddin S; Choy, Jennifer; Huang, Xiayu; La Monaca, Esther; Horn, David M; Wolf, Dieter A; Lipton, Stuart A; Gutierrez, Gustavo J; Brill, Laurence M; Snyder, Evan Y

2016-09-13

Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt. Published by Elsevier Inc.

Different propagation speeds of recalled sequences in plastic spiking neural networks

NASA Astrophysics Data System (ADS)

Huang, Xuhui; Zheng, Zhigang; Hu, Gang; Wu, Si; Rasch, Malte J.

2015-03-01

Neural networks can generate spatiotemporal patterns of spike activity. Sequential activity learning and retrieval have been observed in many brain areas, and e.g. is crucial for coding of episodic memory in the hippocampus or generating temporal patterns during song production in birds. In a recent study, a sequential activity pattern was directly entrained onto the neural activity of the primary visual cortex (V1) of rats and subsequently successfully recalled by a local and transient trigger. It was observed that the speed of activity propagation in coordinates of the retinotopically organized neural tissue was constant during retrieval regardless how the speed of light stimulation sweeping across the visual field during training was varied. It is well known that spike-timing dependent plasticity (STDP) is a potential mechanism for embedding temporal sequences into neural network activity. How training and retrieval speeds relate to each other and how network and learning parameters influence retrieval speeds, however, is not well described. We here theoretically analyze sequential activity learning and retrieval in a recurrent neural network with realistic synaptic short-term dynamics and STDP. Testing multiple STDP rules, we confirm that sequence learning can be achieved by STDP. However, we found that a multiplicative nearest-neighbor (NN) weight update rule generated weight distributions and recall activities that best matched the experiments in V1. Using network simulations and mean-field analysis, we further investigated the learning mechanisms and the influence of network parameters on recall speeds. Our analysis suggests that a multiplicative STDP rule with dominant NN spike interaction might be implemented in V1 since recall speed was almost constant in an NMDA-dominant regime. Interestingly, in an AMPA-dominant regime, neural circuits might exhibit recall speeds that instead follow the change in stimulus speeds. This prediction could be tested in experiments.

The neural basis of understanding the expression of the emotions in man and animals

PubMed Central

Ellsworth, Emily; Adolphs, Ralph

2017-01-01

Abstract Humans cannot help but attribute human emotions to non-human animals. Although such attributions are often regarded as gratuitous anthropomorphisms and held apart from the attributions humans make about each other’s internal states, they may be the product of a general mechanism for flexibly interpreting adaptive behavior. To examine this, we used functional magnetic resonance imaging (fMRI) in humans to compare the neural mechanisms associated with attributing emotions to humans and non-human animal behavior. Although undergoing fMRI, participants first passively observed the facial displays of human, non-human primate and domestic dogs, and subsequently judged the acceptability of emotional (e.g. ‘annoyed’) and facial descriptions (e.g. ‘baring teeth’) for the same images. For all targets, emotion attributions selectively activated regions in prefrontal and anterior temporal cortices associated with causal explanation in prior studies. These regions were similarly activated by both human and non-human targets even during the passive observation task; moreover, the degree of neural similarity was dependent on participants’ self-reported beliefs in the mental capacities of non-human animals. These results encourage a non-anthropocentric view of emotion understanding, one that treats the idea that animals have emotions as no more gratuitous than the idea that humans other than ourselves do. PMID:27803286

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

PubMed

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.

Changing the Spatial Scope of Attention Alters Patterns of Neural Gain in Human Cortex

PubMed Central

Garcia, Javier O.; Rungratsameetaweemana, Nuttida; Sprague, Thomas C.

2014-01-01

Over the last several decades, spatial attention has been shown to influence the activity of neurons in visual cortex in various ways. These conflicting observations have inspired competing models to account for the influence of attention on perception and behavior. Here, we used electroencephalography (EEG) to assess steady-state visual evoked potentials (SSVEP) in human subjects and showed that highly focused spatial attention primarily enhanced neural responses to high-contrast stimuli (response gain), whereas distributed attention primarily enhanced responses to medium-contrast stimuli (contrast gain). Together, these data suggest that different patterns of neural modulation do not reflect fundamentally different neural mechanisms, but instead reflect changes in the spatial extent of attention. PMID:24381272

Powered ankle-foot prosthesis to assist level-ground and stair-descent gaits.

PubMed

Au, Samuel; Berniker, Max; Herr, Hugh

2008-05-01

The human ankle varies impedance and delivers net positive work during the stance period of walking. In contrast, commercially available ankle-foot prostheses are passive during stance, causing many clinical problems for transtibial amputees, including non-symmetric gait patterns, higher gait metabolism, and poorer shock absorption. In this investigation, we develop and evaluate a myoelectric-driven, finite state controller for a powered ankle-foot prosthesis that modulates both impedance and power output during stance. The system employs both sensory inputs measured local to the external prosthesis, and myoelectric inputs measured from residual limb muscles. Using local prosthetic sensing, we first develop two finite state controllers to produce biomimetic movement patterns for level-ground and stair-descent gaits. We then employ myoelectric signals as control commands to manage the transition between these finite state controllers. To transition from level-ground to stairs, the amputee flexes the gastrocnemius muscle, triggering the prosthetic ankle to plantar flex at terminal swing, and initiating the stair-descent state machine algorithm. To transition back to level-ground walking, the amputee flexes the tibialis anterior muscle, triggering the ankle to remain dorsiflexed at terminal swing, and initiating the level-ground state machine algorithm. As a preliminary evaluation of clinical efficacy, we test the device on a transtibial amputee with both the proposed controller and a conventional passive-elastic control. We find that the amputee can robustly transition between the finite state controllers through direct muscle activation, allowing rapid transitioning from level-ground to stair walking patterns. Additionally, we find that the proposed finite state controllers result in a more biomimetic ankle response, producing net propulsive work during level-ground walking and greater shock absorption during stair descent. The results of this study highlight the potential of prosthetic leg controllers that exploit neural signals to trigger terrain-appropriate, local prosthetic leg behaviors.

Experience Modulates Vicarious Freezing in Rats: A Model for Empathy

PubMed Central

Atsak, Piray; Orre, Marie; Bakker, Petra; Cerliani, Leonardo; Roozendaal, Benno

2011-01-01

The study of the neural basis of emotional empathy has received a surge of interest in recent years but mostly employing human neuroimaging. A simpler animal model would pave the way for systematic single cell recordings and invasive manipulations of the brain regions implicated in empathy. Recent evidence has been put forward for the existence of empathy in rodents. In this study, we describe a potential model of empathy in female rats, in which we studied interactions between two rats: a witness observes a demonstrator experiencing a series of footshocks. By comparing the reaction of witnesses with or without previous footshock experience, we examine the role of prior experience as a modulator of empathy. We show that witnesses having previously experienced footshocks, but not naïve ones, display vicarious freezing behavior upon witnessing a cage-mate experiencing footshocks. Strikingly, the demonstrator's behavior was in turn modulated by the behavior of the witness: demonstrators froze more following footshocks if their witness froze more. Previous experiments have shown that rats emit ultrasonic vocalizations (USVs) when receiving footshocks. Thus, the role of USV in triggering vicarious freezing in our paradigm is examined. We found that experienced witness-demonstrator pairs emitted more USVs than naïve witness-demonstrator pairs, but the number of USVs was correlated with freezing in demonstrators, not in witnesses. Furthermore, playing back the USVs, recorded from witness-demonstrator pairs during the empathy test, did not induce vicarious freezing behavior in experienced witnesses. Thus, our findings confirm that vicarious freezing can be triggered in rats, and moreover it can be modulated by prior experience. Additionally, our result suggests that vicarious freezing is not triggered by USVs per se and it influences back onto the behavior of the demonstrator that had elicited the vicarious freezing in witnesses, introducing a paradigm to study empathy as a social loop. PMID:21765921

In vitro effects of Epidiferphane™ on adult human neural progenitor cells

USDA-ARS?s Scientific Manuscript database

Neural stem cells have the capacity to respond to their environment, migrate to the injury site and generate functional cell types, and thus they hold great promise for cell therapies. In addition to representing a source for central nervous system (CNS) repair, neural stem and progenitor cells als...

Critical Branching Neural Networks

ERIC Educational Resources Information Center

Kello, Christopher T.

2013-01-01

It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical…

A GPU-accelerated cortical neural network model for visually guided robot navigation.

PubMed

Beyeler, Michael; Oros, Nicolas; Dutt, Nikil; Krichmar, Jeffrey L

2015-12-01

Humans and other terrestrial animals use vision to traverse novel cluttered environments with apparent ease. On one hand, although much is known about the behavioral dynamics of steering in humans, it remains unclear how relevant perceptual variables might be represented in the brain. On the other hand, although a wealth of data exists about the neural circuitry that is concerned with the perception of self-motion variables such as the current direction of travel, little research has been devoted to investigating how this neural circuitry may relate to active steering control. Here we present a cortical neural network model for visually guided navigation that has been embodied on a physical robot exploring a real-world environment. The model includes a rate based motion energy model for area V1, and a spiking neural network model for cortical area MT. The model generates a cortical representation of optic flow, determines the position of objects based on motion discontinuities, and combines these signals with the representation of a goal location to produce motor commands that successfully steer the robot around obstacles toward the goal. The model produces robot trajectories that closely match human behavioral data. This study demonstrates how neural signals in a model of cortical area MT might provide sufficient motion information to steer a physical robot on human-like paths around obstacles in a real-world environment, and exemplifies the importance of embodiment, as behavior is deeply coupled not only with the underlying model of brain function, but also with the anatomical constraints of the physical body it controls. Copyright © 2015 Elsevier Ltd. All rights reserved.

Application of Fault Management Theory to the Quantitative Selection of a Launch Vehicle Abort Trigger Suite

NASA Technical Reports Server (NTRS)

Lo, Yunnhon; Johnson, Stephen B.; Breckenridge, Jonathan T.

2014-01-01

This paper describes the quantitative application of the theory of System Health Management and its operational subset, Fault Management, to the selection of abort triggers for a human-rated launch vehicle, the United States' National Aeronautics and Space Administration's (NASA) Space Launch System (SLS). The results demonstrate the efficacy of the theory to assess the effectiveness of candidate failure detection and response mechanisms to protect humans from time-critical and severe hazards. The quantitative method was successfully used on the SLS to aid selection of its suite of abort triggers.

Application of Fault Management Theory to the Quantitative Selection of a Launch Vehicle Abort Trigger Suite

NASA Technical Reports Server (NTRS)

Lo, Yunnhon; Johnson, Stephen B.; Breckenridge, Jonathan T.

2014-01-01

This paper describes the quantitative application of the theory of System Health Management and its operational subset, Fault Management, to the selection of Abort Triggers for a human-rated launch vehicle, the United States' National Aeronautics and Space Administration's (NASA) Space Launch System (SLS). The results demonstrate the efficacy of the theory to assess the effectiveness of candidate failure detection and response mechanisms to protect humans from time-critical and severe hazards. The quantitative method was successfully used on the SLS to aid selection of its suite of Abort Triggers.

This Neural Implant is designed to be implanted in the Human Central and Nervous System

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

A new class of neural implants being developed at the Livermore Lab are the first clinical quality devices capable of two-way conversations with the human nervous systems. Unlike existing interfaces that only sense or only stimulate, these devices are capable of stimulating and sensing using both electric and chemical signals.

This Neural Implant is designed to be implanted in the Human Central and Nervous System

ScienceCinema

None

2018-06-12

A new class of neural implants being developed at the Livermore Lab are the first clinical quality devices capable of two-way conversations with the human nervous systems. Unlike existing interfaces that only sense or only stimulate, these devices are capable of stimulating and sensing using both electric and chemical signals.

EVALUATION OF HUMAN NEURAL PROGENITOR CELLS FOR DEVELOPMENTAL NEUROTOXICITY SCREENING: TIME COURSE OF EFFECTS ON CELL PROLIFERATION AND VIABILITY.

EPA Science Inventory

Current testing methods for developmental neurotoxicity (DNT) make evaluation of the effects of large numbers of chemicals impractical and prohibitively expensive. As such, we are evaluating human neural progenitor cells (NPCs) as a screen for DNT. ReNcell CX (ReN CX) cells are a...

Deep Neural Networks as a Computational Model for Human Shape Sensitivity

PubMed Central

Op de Beeck, Hans P.

2016-01-01

Theories of object recognition agree that shape is of primordial importance, but there is no consensus about how shape might be represented, and so far attempts to implement a model of shape perception that would work with realistic stimuli have largely failed. Recent studies suggest that state-of-the-art convolutional ‘deep’ neural networks (DNNs) capture important aspects of human object perception. We hypothesized that these successes might be partially related to a human-like representation of object shape. Here we demonstrate that sensitivity for shape features, characteristic to human and primate vision, emerges in DNNs when trained for generic object recognition from natural photographs. We show that these models explain human shape judgments for several benchmark behavioral and neural stimulus sets on which earlier models mostly failed. In particular, although never explicitly trained for such stimuli, DNNs develop acute sensitivity to minute variations in shape and to non-accidental properties that have long been implicated to form the basis for object recognition. Even more strikingly, when tested with a challenging stimulus set in which shape and category membership are dissociated, the most complex model architectures capture human shape sensitivity as well as some aspects of the category structure that emerges from human judgments. As a whole, these results indicate that convolutional neural networks not only learn physically correct representations of object categories but also develop perceptually accurate representational spaces of shapes. An even more complete model of human object representations might be in sight by training deep architectures for multiple tasks, which is so characteristic in human development. PMID:27124699

Learning Perfectly Secure Cryptography to Protect Communications with Adversarial Neural Cryptography

PubMed Central

2018-01-01

Researches in Artificial Intelligence (AI) have achieved many important breakthroughs, especially in recent years. In some cases, AI learns alone from scratch and performs human tasks faster and better than humans. With the recent advances in AI, it is natural to wonder whether Artificial Neural Networks will be used to successfully create or break cryptographic algorithms. Bibliographic review shows the main approach to this problem have been addressed throughout complex Neural Networks, but without understanding or proving the security of the generated model. This paper presents an analysis of the security of cryptographic algorithms generated by a new technique called Adversarial Neural Cryptography (ANC). Using the proposed network, we show limitations and directions to improve the current approach of ANC. Training the proposed Artificial Neural Network with the improved model of ANC, we show that artificially intelligent agents can learn the unbreakable One-Time Pad (OTP) algorithm, without human knowledge, to communicate securely through an insecure communication channel. This paper shows in which conditions an AI agent can learn a secure encryption scheme. However, it also shows that, without a stronger adversary, it is more likely to obtain an insecure one. PMID:29695066

Learning Perfectly Secure Cryptography to Protect Communications with Adversarial Neural Cryptography.

PubMed

Coutinho, Murilo; de Oliveira Albuquerque, Robson; Borges, Fábio; García Villalba, Luis Javier; Kim, Tai-Hoon

2018-04-24

Researches in Artificial Intelligence (AI) have achieved many important breakthroughs, especially in recent years. In some cases, AI learns alone from scratch and performs human tasks faster and better than humans. With the recent advances in AI, it is natural to wonder whether Artificial Neural Networks will be used to successfully create or break cryptographic algorithms. Bibliographic review shows the main approach to this problem have been addressed throughout complex Neural Networks, but without understanding or proving the security of the generated model. This paper presents an analysis of the security of cryptographic algorithms generated by a new technique called Adversarial Neural Cryptography (ANC). Using the proposed network, we show limitations and directions to improve the current approach of ANC. Training the proposed Artificial Neural Network with the improved model of ANC, we show that artificially intelligent agents can learn the unbreakable One-Time Pad (OTP) algorithm, without human knowledge, to communicate securely through an insecure communication channel. This paper shows in which conditions an AI agent can learn a secure encryption scheme. However, it also shows that, without a stronger adversary, it is more likely to obtain an insecure one.

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

PubMed Central

Sánchez, Daniela; Melin, Patricia

2017-01-01

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. PMID:28894461

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

PubMed

Sánchez, Daniela; Melin, Patricia; Castillo, Oscar

2017-01-01

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.

A tale of two species: neural integration in zebrafish and monkeys

PubMed Central

Joshua, Mati; Lisberger, Stephen G.

2014-01-01

Selection of a model organism creates a tension between competing constraints. The recent explosion of modern molecular techniques has revolutionized the analysis of neural systems in organisms that are amenable to genetic techniques. Yet, the non-human primate remains the gold-standard for the analysis of the neural basis of behavior, and as a bridge to the operation of the human brain. The challenge is to generalize across species in a way that exposes the operation of circuits as well as the relationship of circuits to behavior. Eye movements provide an opportunity to cross the bridge from mechanism to behavior through research on diverse species. Here, we review experiments and computational studies on a circuit function called “neural integration” that occurs in the brainstems of larval zebrafish, non-human primates, and species “in between”. We show that analysis of circuit structure using modern molecular and imaging approaches in zebrafish has remarkable explanatory power for the details of the responses of integrator neurons in the monkey. The combination of research from the two species has led to a much stronger hypothesis for the implementation of the neural integrator than could have been achieved using either species alone. PMID:24797331

Navigating conjugated polymer actuated neural probes in a brain phantom

NASA Astrophysics Data System (ADS)

Daneshvar, Eugene D.; Kipke, Daryl; Smela, Elisabeth

2012-04-01

Neural probe insertion methods have a direct impact on the longevity of the device in the brain. Initial tissue and vascular damage caused by the probe entering the brain triggers a chronic tissue response that is known to attenuate neural recordings and ultimately encapsulate the probes. Smaller devices have been found to evoke reduced inflammatory response. One way to record from undamaged neural networks may be to position the electrode sites away from the probe. To investigate this approach, we are developing probes with controllably movable electrode projections, which would move outside of the zone that is damaged by the insertion of the larger probe. The objective of this study was to test the capability of conjugated polymer bilayer actuators to actuate neural electrode projections from a probe shank into a transparent brain phantom. Parylene neural probe devices, having five electrode projections with actuating segments and with varying widths (50 - 250 μm) and lengths (200 - 1000 μm) were fabricated. The electroactive polymer polypyrrole (PPy) was used to bend or flatten the projections. The devices were inserted into the brain phantom using an electronic microdrive while simultaneously activating the actuators. Deflections were quantified based on video images. The electrode projections were successfully controlled to either remain flat or to actuate out-of-plane and into the brain phantom during insertion. The projection width had a significant effect on their ability to deflect within the phantom, with thinner probes deflecting but not the wider ones. Thus, small integrated conjugated polymer actuators may enable multiple neuro-experiments and applications not possible before.

Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition.

PubMed

Su, Zhenghui; Zhang, Yanqi; Liao, Baojian; Zhong, Xiaofen; Chen, Xin; Wang, Haitao; Guo, Yiping; Shan, Yongli; Wang, Lihui; Pan, Guangjin

2018-03-23

During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain neural progenitor cells along the rostral-caudal axis. We report that neural patterning determination occurs at the very early stage in this differentiation. Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the "default" rostral fate at the beginning of differentiation. Inhibition of glycogen synthase kinase 3β (GSK3β) through CHIR99021 application sustained transient expression of the transcription factor NANOG at early differentiation stages through Wnt signaling. Wnt signaling and NANOG antagonized OTX2 and, in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

The role of symmetry in neural networks and their Laplacian spectra.

PubMed

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

2016-11-01

Human and animal nervous systems constitute complexly wired networks that form the infrastructure for neural processing and integration of information. The organization of these neural networks can be analyzed using the so-called Laplacian spectrum, providing a mathematical tool to produce systems-level network fingerprints. In this article, we examine a characteristic central peak in the spectrum of neural networks, including anatomical brain network maps of the mouse, cat and macaque, as well as anatomical and functional network maps of human brain connectivity. We link the occurrence of this central peak to the level of symmetry in neural networks, an intriguing aspect of network organization resulting from network elements that exhibit similar wiring patterns. Specifically, we propose a measure to capture the global level of symmetry of a network and show that, for both empirical networks and network models, the height of the main peak in the Laplacian spectrum is strongly related to node symmetry in the underlying network. Moreover, examination of spectra of duplication-based model networks shows that neural spectra are best approximated using a trade-off between duplication and diversification. Taken together, our results facilitate a better understanding of neural network spectra and the importance of symmetry in neural networks. Copyright © 2016 Elsevier Inc. All rights reserved.

The 2008 M7.9 Wenchuan earthquake - a human-caused event

NASA Astrophysics Data System (ADS)

Klose, C. D.

2013-12-01

A catalog of global human-caused earthquakes shows statistical evidence that the triggering of earthquakes by large-scale geoengineering activities depends on geological and tectonic constrains (in Klose 2013). Such geoengineering activities also include the filling of water reservoirs. This presentation illuminates mechanical and statistical aspects of the 2008 M7.9 Wenchuan earthquake in light of the hypothesis of being NOT human-caused. However, available data suggest that the Wenchuan earthquake was triggered by the filling of the Zipungpu water reservoir 30 months prior to the mainshock. The reservoir spatially extended parallel and near to the main Beichuan fault zone in a highly stressed reverse fault regime. It is mechanically evident that reverse faults tend to be very trigger-sensitive due to mass shifts (static loads) that occur on the surface of the Earth's crust. These circumstances made a triggering of a seismic event of this magnitude at this location possible (in Klose 2008, 2012). The data show that the Wenchuan earthquake is not an outlier. From a statistical view point, the earthquake falls into the upper range of the family of reverse fault earthquakes that were caused by humans worldwide.

Capturing the temporal evolution of choice across prefrontal cortex

PubMed Central

Hunt, Laurence T; Behrens, Timothy EJ; Hosokawa, Takayuki; Wallis, Jonathan D; Kennerley, Steven W

2015-01-01

Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making. DOI: http://dx.doi.org/10.7554/eLife.11945.001 PMID:26653139

Human fatigue expression recognition through image-based dynamic multi-information and bimodal deep learning

NASA Astrophysics Data System (ADS)

Zhao, Lei; Wang, Zengcai; Wang, Xiaojin; Qi, Yazhou; Liu, Qing; Zhang, Guoxin

2016-09-01

Human fatigue is an important cause of traffic accidents. To improve the safety of transportation, we propose, in this paper, a framework for fatigue expression recognition using image-based facial dynamic multi-information and a bimodal deep neural network. First, the landmark of face region and the texture of eye region, which complement each other in fatigue expression recognition, are extracted from facial image sequences captured by a single camera. Then, two stacked autoencoder neural networks are trained for landmark and texture, respectively. Finally, the two trained neural networks are combined by learning a joint layer on top of them to construct a bimodal deep neural network. The model can be used to extract a unified representation that fuses landmark and texture modalities together and classify fatigue expressions accurately. The proposed system is tested on a human fatigue dataset obtained from an actual driving environment. The experimental results demonstrate that the proposed method performs stably and robustly, and that the average accuracy achieves 96.2%.

The auditory representation of speech sounds in human motor cortex

PubMed Central

Cheung, Connie; Hamilton, Liberty S; Johnson, Keith; Chang, Edward F

2016-01-01

In humans, listening to speech evokes neural responses in the motor cortex. This has been controversially interpreted as evidence that speech sounds are processed as articulatory gestures. However, it is unclear what information is actually encoded by such neural activity. We used high-density direct human cortical recordings while participants spoke and listened to speech sounds. Motor cortex neural patterns during listening were substantially different than during articulation of the same sounds. During listening, we observed neural activity in the superior and inferior regions of ventral motor cortex. During speaking, responses were distributed throughout somatotopic representations of speech articulators in motor cortex. The structure of responses in motor cortex during listening was organized along acoustic features similar to auditory cortex, rather than along articulatory features as during speaking. Motor cortex does not contain articulatory representations of perceived actions in speech, but rather, represents auditory vocal information. DOI: http://dx.doi.org/10.7554/eLife.12577.001 PMID:26943778

Mastering the game of Go without human knowledge.

PubMed

Silver, David; Schrittwieser, Julian; Simonyan, Karen; Antonoglou, Ioannis; Huang, Aja; Guez, Arthur; Hubert, Thomas; Baker, Lucas; Lai, Matthew; Bolton, Adrian; Chen, Yutian; Lillicrap, Timothy; Hui, Fan; Sifre, Laurent; van den Driessche, George; Graepel, Thore; Hassabis, Demis

2017-10-18

A long-standing goal of artificial intelligence is an algorithm that learns, tabula rasa, superhuman proficiency in challenging domains. Recently, AlphaGo became the first program to defeat a world champion in the game of Go. The tree search in AlphaGo evaluated positions and selected moves using deep neural networks. These neural networks were trained by supervised learning from human expert moves, and by reinforcement learning from self-play. Here we introduce an algorithm based solely on reinforcement learning, without human data, guidance or domain knowledge beyond game rules. AlphaGo becomes its own teacher: a neural network is trained to predict AlphaGo's own move selections and also the winner of AlphaGo's games. This neural network improves the strength of the tree search, resulting in higher quality move selection and stronger self-play in the next iteration. Starting tabula rasa, our new program AlphaGo Zero achieved superhuman performance, winning 100-0 against the previously published, champion-defeating AlphaGo.

Mastering the game of Go without human knowledge

NASA Astrophysics Data System (ADS)

Silver, David; Schrittwieser, Julian; Simonyan, Karen; Antonoglou, Ioannis; Huang, Aja; Guez, Arthur; Hubert, Thomas; Baker, Lucas; Lai, Matthew; Bolton, Adrian; Chen, Yutian; Lillicrap, Timothy; Hui, Fan; Sifre, Laurent; van den Driessche, George; Graepel, Thore; Hassabis, Demis

2017-10-01

A long-standing goal of artificial intelligence is an algorithm that learns, tabula rasa, superhuman proficiency in challenging domains. Recently, AlphaGo became the first program to defeat a world champion in the game of Go. The tree search in AlphaGo evaluated positions and selected moves using deep neural networks. These neural networks were trained by supervised learning from human expert moves, and by reinforcement learning from self-play. Here we introduce an algorithm based solely on reinforcement learning, without human data, guidance or domain knowledge beyond game rules. AlphaGo becomes its own teacher: a neural network is trained to predict AlphaGo’s own move selections and also the winner of AlphaGo’s games. This neural network improves the strength of the tree search, resulting in higher quality move selection and stronger self-play in the next iteration. Starting tabula rasa, our new program AlphaGo Zero achieved superhuman performance, winning 100-0 against the previously published, champion-defeating AlphaGo.

A quantitative framework to evaluate modeling of cortical development by neural stem cells

PubMed Central

Stein, Jason L.; de la Torre-Ubieta, Luis; Tian, Yuan; Parikshak, Neelroop N.; Hernandez, Israel A.; Marchetto, Maria C.; Baker, Dylan K.; Lu, Daning; Hinman, Cassidy R.; Lowe, Jennifer K.; Wexler, Eric M.; Muotri, Alysson R.; Gage, Fred H.; Kosik, Kenneth S.; Geschwind, Daniel H.

2014-01-01

Summary Neural stem cells have been adopted to model a wide range of neuropsychiatric conditions in vitro. However, how well such models correspond to in vivo brain has not been evaluated in an unbiased, comprehensive manner. We used transcriptomic analyses to compare in vitro systems to developing human fetal brain and observed strong conservation of in vivo gene expression and network architecture in differentiating primary human neural progenitor cells (phNPCs). Conserved modules are enriched in genes associated with ASD, supporting the utility of phNPCs for studying neuropsychiatric disease. We also developed and validated a machine learning approach called CoNTExT that identifies the developmental maturity and regional identity of in vitro models. We observed strong differences between in vitro models, including hiPSC-derived neural progenitors from multiple laboratories. This work provides a systems biology framework for evaluating in vitro systems and supports their value in studying the molecular mechanisms of human neurodevelopmental disease. PMID:24991955

Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy

PubMed Central

2013-01-01

Introduction Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury. Methods Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility. Results There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased mortality compared with control pups. Conclusions Significant injury to the enteric nervous system occurs in both human and experimental necrotizing enterocolitis. Neural stem cell transplantation may represent a novel future therapy for patients with necrotizing enterocolitis. PMID:24423414

A three-dimensional human neural cell culture model of Alzheimer's disease.

PubMed

Choi, Se Hoon; Kim, Young Hye; Hebisch, Matthias; Sliwinski, Christopher; Lee, Seungkyu; D'Avanzo, Carla; Chen, Hechao; Hooli, Basavaraj; Asselin, Caroline; Muffat, Julien; Klee, Justin B; Zhang, Can; Wainger, Brian J; Peitz, Michael; Kovacs, Dora M; Woolf, Clifford J; Wagner, Steven L; Tanzi, Rudolph E; Kim, Doo Yeon

2014-11-13

Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer's disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.

In vitro differentiation of neural cells from human adipose tissue derived stromal cells.

PubMed

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.

The Neural Crest in Cardiac Congenital Anomalies

PubMed Central

Keyte, Anna; Hutson, Mary Redmond

2012-01-01

This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions. PMID:22595346

Functional metabolic interactions of human neuron-astrocyte 3D in vitro networks

PubMed Central

Simão, Daniel; Terrasso, Ana P.; Teixeira, Ana P.; Brito, Catarina; Sonnewald, Ursula; Alves, Paula M.

2016-01-01

The generation of human neural tissue-like 3D structures holds great promise for disease modeling, drug discovery and regenerative medicine strategies. Promoting the establishment of complex cell-cell interactions, 3D culture systems enable the development of human cell-based models with increased physiological relevance, over monolayer cultures. Here, we demonstrate the establishment of neuronal and astrocytic metabolic signatures and shuttles in a human 3D neural cell model, namely the glutamine-glutamate-GABA shuttle. This was indicated by labeling of neuronal GABA following incubation with the glia-specific substrate [2-13C]acetate, which decreased by methionine sulfoximine-induced inhibition of the glial enzyme glutamine synthetase. Cell metabolic specialization was further demonstrated by higher pyruvate carboxylase-derived labeling in glutamine than in glutamate, indicating its activity in astrocytes and not in neurons. Exposure to the neurotoxin acrylamide resulted in intracellular accumulation of glutamate and decreased GABA synthesis. These results suggest an acrylamide-induced impairment of neuronal synaptic vesicle trafficking and imbalanced glutamine-glutamate-GABA cycle, due to loss of cell-cell contacts at synaptic sites. This work demonstrates, for the first time to our knowledge, that neural differentiation of human cells in a 3D setting recapitulates neuronal-astrocytic metabolic interactions, highlighting the relevance of these models for toxicology and better understanding the crosstalk between human neural cells. PMID:27619889

Functional metabolic interactions of human neuron-astrocyte 3D in vitro networks.

PubMed

Simão, Daniel; Terrasso, Ana P; Teixeira, Ana P; Brito, Catarina; Sonnewald, Ursula; Alves, Paula M

2016-09-13

The generation of human neural tissue-like 3D structures holds great promise for disease modeling, drug discovery and regenerative medicine strategies. Promoting the establishment of complex cell-cell interactions, 3D culture systems enable the development of human cell-based models with increased physiological relevance, over monolayer cultures. Here, we demonstrate the establishment of neuronal and astrocytic metabolic signatures and shuttles in a human 3D neural cell model, namely the glutamine-glutamate-GABA shuttle. This was indicated by labeling of neuronal GABA following incubation with the glia-specific substrate [2-(13)C]acetate, which decreased by methionine sulfoximine-induced inhibition of the glial enzyme glutamine synthetase. Cell metabolic specialization was further demonstrated by higher pyruvate carboxylase-derived labeling in glutamine than in glutamate, indicating its activity in astrocytes and not in neurons. Exposure to the neurotoxin acrylamide resulted in intracellular accumulation of glutamate and decreased GABA synthesis. These results suggest an acrylamide-induced impairment of neuronal synaptic vesicle trafficking and imbalanced glutamine-glutamate-GABA cycle, due to loss of cell-cell contacts at synaptic sites. This work demonstrates, for the first time to our knowledge, that neural differentiation of human cells in a 3D setting recapitulates neuronal-astrocytic metabolic interactions, highlighting the relevance of these models for toxicology and better understanding the crosstalk between human neural cells.

Bottom-up driven involuntary auditory evoked field change: constant sound sequencing amplifies but does not sharpen neural activity.

PubMed

Okamoto, Hidehiko; Stracke, Henning; Lagemann, Lothar; Pantev, Christo

2010-01-01

The capability of involuntarily tracking certain sound signals during the simultaneous presence of noise is essential in human daily life. Previous studies have demonstrated that top-down auditory focused attention can enhance excitatory and inhibitory neural activity, resulting in sharpening of frequency tuning of auditory neurons. In the present study, we investigated bottom-up driven involuntary neural processing of sound signals in noisy environments by means of magnetoencephalography. We contrasted two sound signal sequencing conditions: "constant sequencing" versus "random sequencing." Based on a pool of 16 different frequencies, either identical (constant sequencing) or pseudorandomly chosen (random sequencing) test frequencies were presented blockwise together with band-eliminated noises to nonattending subjects. The results demonstrated that the auditory evoked fields elicited in the constant sequencing condition were significantly enhanced compared with the random sequencing condition. However, the enhancement was not significantly different between different band-eliminated noise conditions. Thus the present study confirms that by constant sound signal sequencing under nonattentive listening the neural activity in human auditory cortex can be enhanced, but not sharpened. Our results indicate that bottom-up driven involuntary neural processing may mainly amplify excitatory neural networks, but may not effectively enhance inhibitory neural circuits.

The Neural Basis of Vocal Pitch Imitation in Humans.

PubMed

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.

Identifying a Network of Brain Regions Involved in Aversion-Related Processing: A Cross-Species Translational Investigation

PubMed Central

Hayes, Dave J.; Northoff, Georg

2011-01-01

The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed. PMID:22102836

A neural circuitry that emphasizes spinal feedback generates diverse behaviours of human locomotion

PubMed Central

Song, Seungmoon; Geyer, Hartmut

2015-01-01

Neural networks along the spinal cord contribute substantially to generating locomotion behaviours in humans and other legged animals. However, the neural circuitry involved in this spinal control remains unclear. We here propose a specific circuitry that emphasizes feedback integration over central pattern generation. The circuitry is based on neurophysiologically plausible muscle-reflex pathways that are organized in 10 spinal modules realizing limb functions essential to legged systems in stance and swing. These modules are combined with a supraspinal control layer that adjusts the desired foot placements and selects the leg that is to transition into swing control during double support. Using physics-based simulation, we test the proposed circuitry in a neuromuscular human model that includes neural transmission delays, musculotendon dynamics and compliant foot–ground contacts. We find that the control network is sufficient to compose steady and transitional 3-D locomotion behaviours including walking and running, acceleration and deceleration, slope and stair negotiation, turning, and deliberate obstacle avoidance. The results suggest feedback integration to be functionally more important than central pattern generation in human locomotion across behaviours. In addition, the proposed control architecture may serve as a guide in the search for the neurophysiological origin and circuitry of spinal control in humans. PMID:25920414

Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease progression and neuropathogenesis

PubMed Central

Banerjee, Anupam; Strazza, Marianne; Wigdahl, Brian; Pirrone, Vanessa; Meucci, Olimpia

2013-01-01

About one third of acquired immunodeficiency syndrome cases in the USA have been attributed to the use of injected addictive drugs, frequently involving opioids like heroin and morphine, establishing them as significant predisposing risk factors for contracting human immuno-deficiency virus type 1 (HIV-1). Accumulating evidence from in vitro and in vivo experimental systems indicates that opioids act in concert with HIV-1 proteins to exacerbate dysregulation of neural and immune cell function and survival through diverse molecular mechanisms. In contrast, the impact of opioid exposure and withdrawal on the viral life cycle and HIV-1 disease progression itself is unclear, with conflicting reports emerging from the simian immunodeficiency virus and simian–human immunodeficiency virus infection models. However, these studies suggest a potential role of opioids in elevated viral production. Because human microglia, astrocytes, CD4+ T lymphocytes, and monocyte-derived macrophages express opioid receptors, it is likely that intracellular signaling events triggered by morphine facilitate enhancement of HIV-1 infection in these target cell populations. This review highlights the biochemical changes that accompany prolonged exposure to and withdrawal from morphine that synergize with HIV-1 proteins to disrupt normal cellular physiological functions especially within the central nervous system. More importantly, it collates evidence from epidemiological studies, animal models, and heterologous cell systems to propose a mechanistic link between such physiological adaptations and direct modulation of HIV-1 production. Understanding the opioid–HIV-1 interface at the molecular level is vitally important in designing better treatment strategies for HIV-1-infected patients who abuse opioids. PMID:21735315

Comparison of deep neural networks to spatio-temporal cortical dynamics of human visual object recognition reveals hierarchical correspondence

PubMed Central

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

2016-01-01

The complex multi-stage architecture of cortical visual pathways provides the neural basis for efficient visual object recognition in humans. However, the stage-wise computations therein remain poorly understood. Here, we compared temporal (magnetoencephalography) and spatial (functional MRI) visual brain representations with representations in an artificial deep neural network (DNN) tuned to the statistics of real-world visual recognition. We showed that the DNN captured the stages of human visual processing in both time and space from early visual areas towards the dorsal and ventral streams. Further investigation of crucial DNN parameters revealed that while model architecture was important, training on real-world categorization was necessary to enforce spatio-temporal hierarchical relationships with the brain. Together our results provide an algorithmically informed view on the spatio-temporal dynamics of visual object recognition in the human visual brain. PMID:27282108

Comparison of deep neural networks to spatio-temporal cortical dynamics of human visual object recognition reveals hierarchical correspondence.

PubMed

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

2016-06-10

The complex multi-stage architecture of cortical visual pathways provides the neural basis for efficient visual object recognition in humans. However, the stage-wise computations therein remain poorly understood. Here, we compared temporal (magnetoencephalography) and spatial (functional MRI) visual brain representations with representations in an artificial deep neural network (DNN) tuned to the statistics of real-world visual recognition. We showed that the DNN captured the stages of human visual processing in both time and space from early visual areas towards the dorsal and ventral streams. Further investigation of crucial DNN parameters revealed that while model architecture was important, training on real-world categorization was necessary to enforce spatio-temporal hierarchical relationships with the brain. Together our results provide an algorithmically informed view on the spatio-temporal dynamics of visual object recognition in the human visual brain.

Right hemispheric dominance and interhemispheric cooperation in gaze-triggered reflexive shift of attention.

PubMed

Okada, Takashi; Sato, Wataru; Kubota, Yasutaka; Toichi, Motomi; Murai, Toshiya

2012-03-01

The neural substrate for the processing of gaze remains unknown. The aim of the present study was to clarify which hemisphere dominantly processes and whether bilateral hemispheres cooperate with each other in gaze-triggered reflexive shift of attention. Twenty-eight normal subjects were tested. The non-predictive gaze cues were presented either in unilateral or bilateral visual fields. The subjects localized the target as soon as possible. Reaction times (RT) were shorter when gaze-cues were congruent toward than away from targets, whichever visual field they were presented in. RT were shorter in left than right visual field presentations. RT in mono-directional bilateral presentations were shorter than both of those in left and right presentations. When bi-directional bilateral cues were presented, RT were faster when valid cues were presented in the left than right visual fields. The right hemisphere appears to be dominant, and there is interhemispheric cooperation in gaze-triggered reflexive shift of attention. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.

Munc13 homology domain-1 in CAPS/UNC31 mediates SNARE binding required for priming vesicle exocytosis.

PubMed

Khodthong, Chuenchanok; Kabachinski, Greg; James, Declan J; Martin, Thomas F J

2011-08-03

Neuropeptide and peptide hormone secretion from neural and endocrine cells occurs by Ca(2+)-triggered dense-core vesicle exocytosis. The membrane fusion machinery consisting of vesicle and plasma membrane SNARE proteins needs to be assembled for Ca(2+)-triggered vesicle exocytosis. The related Munc13 and CAPS/UNC31 proteins that prime vesicle exocytosis are proposed to promote SNARE complex assembly. CAPS binds SNARE proteins and stimulates SNARE complex formation on liposomes, but the relevance of SNARE binding to CAPS function in cells had not been determined. Here we identify a core SNARE-binding domain in CAPS as corresponding to Munc13 homology domain-1 (MHD1). CAPS lacking a single helix in MHD1 was unable to bind SNARE proteins or to support the Ca(2+)-triggered exocytosis of either docked or newly arrived dense-core vesicles. The results show that MHD1 is a SNARE-binding domain and that SNARE protein binding is essential for CAPS function in dense-core vesicle exocytosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Role of vitamin D in regulating the neural stem cells of mouse model with multiple sclerosis.

PubMed

Gu, S-G; Wang, C-J; Zhao, G; Li, G-Y

2015-11-01

Multiple sclerosis (MS) is an autoimmune disease that results with a damaged myelin sheath as a result, there is an impairment of nerve impulse conduction. The medication for MS is able to delay its progression, but complete recovery is impossible. Recent studies with neural stem cells have promising results in treating as well as to recover the damaged nerves, but research on in vivo model system is limited in this aspect. Here we are able to successfully establish an MS mice model by injecting with myelin basic protein and we studied the neural stem cell response in supplement with vitamin D. Through histology we provide strong evidence that the MS pathogenesis is reverted on response to vitamin D. We also identified through immunohistochemistry and western blotting that the vitamin D has the ability to trigger neural stem cells, and thereby it assist in recovery from MS. Further, their roles in preventing as well as delaying the MS development are also proven. The role of vitamin D has also cross checked with the help of tunnel assay. Overall, our results conclude that the lesion associated apoptotic signals are reduced on administrated with vitamin D. The present data help to design a new therapeutic intervention to cure MS.

Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia

PubMed Central

Bochner, David N.; Sapp, Richard W.; Adelson, Jaimie D.; Zhang, Siyu; Lee, Hanmi; Djurisic, Maja; Syken, Josh; Dan, Yang; Shatz, Carla J.

2015-01-01

During critical periods of development, the brain easily changes in response to environmental stimuli, but this neural plasticity declines by adulthood. By acutely disrupting paired immunoglobulin-like receptor B(PirB) function at specific ages, we show that PirB actively represses neural plasticity throughout life. We disrupted PirB function either by genetically introducing a conditional PirB allele into mice or by minipump infusion of a soluble PirB ectodomain (sPirB) into mouse visual cortex. We found that neural plasticity, as measured by depriving mice of vision in one eye and testing ocular dominance, was enhanced by this treatment both during the critical period and when PirB function was disrupted in adulthood. Acute blockade of PirB triggered the formation of new functional synapses, as indicated by increases in miniature excitatory postsynaptic current (mEPSC) frequency and spine density on dendrites of layer 5 pyramidal neurons. In addition, recovery from amblyopia— the decline in visual acuity and spine density resulting from long-term monocular deprivation— was possible after a 1-week infusion of sPirB after the deprivation period. Thus, neural plasticity in adult visual cortex is actively repressed and can be enhanced by blocking PirB function. PMID:25320232

Synthesizing animal and human behavior research via neural network learning theory.

PubMed

Tryon, W W

1995-12-01

Animal and human research have been "divorced" since approximately 1968. Several recent articles have tried to persuade behavior therapists of the merits of animal research. Three reasons are given concerning why disinterest in animal research is so widespread: (1) functional explanations are given for animals, and cognitive explanations are given for humans; (2) serial symbol manipulating models are used to explain human behavior; and (3) human learning was assumed, thereby removing it as something to be explained. Brain-inspired connectionist neural networks, collectively referred to as neural network learning theory (NNLT), are briefly described, and a spectrum of their accomplishments from simple conditioning through speech is outlined. Five benefits that behavior therapists can derive from NNLT are described. They include (a) enhanced professional identity derived from a comprehensive learning theory, (b) improved interdisciplinary collaboration both clinically and scientifically, (c) renewed perceived relevance of animal research, (d) access to plausible proximal causal mechanisms capable of explaining operant conditioning, and (e) an inherently developmental perspective.

Face Recognition in Humans and Machines

NASA Astrophysics Data System (ADS)

O'Toole, Alice; Tistarelli, Massimo

The study of human face recognition by psychologists and neuroscientists has run parallel to the development of automatic face recognition technologies by computer scientists and engineers. In both cases, there are analogous steps of data acquisition, image processing, and the formation of representations that can support the complex and diverse tasks we accomplish with faces. These processes can be understood and compared in the context of their neural and computational implementations. In this chapter, we present the essential elements of face recognition by humans and machines, taking a perspective that spans psychological, neural, and computational approaches. From the human side, we overview the methods and techniques used in the neurobiology of face recognition, the underlying neural architecture of the system, the role of visual attention, and the nature of the representations that emerges. From the computational side, we discuss face recognition technologies and the strategies they use to overcome challenges to robust operation over viewing parameters. Finally, we conclude the chapter with a look at some recent studies that compare human and machine performances at face recognition.

Detecting phase transitions in a neural network and its application to classification of syndromes in traditional Chinese medicine

NASA Astrophysics Data System (ADS)

Chen, J.; Xi, G.; Wang, W.

2008-02-01

Detecting phase transitions in neural networks (determined or random) presents a challenging subject for phase transitions play a key role in human brain activity. In this paper, we detect numerically phase transitions in two types of random neural network(RNN) under proper parameters.

The anatomy of the intralingual neural interconnections.

PubMed

Păduraru, Dumitru; Rusu, Mugurel Constantin

2013-08-01

The intrinsic lingual neural interconnections are overlooked. It was hypothesized that intralingual anatomically well defined anastomoses interconnect the somatic and autonomic neural systems of the tongue. It was thus aimed to evaluate the intralingual neural scaffold in human tongues. Human tongue samples (ten adult and one pediatric) were microdissected (4.5 magnification). In the interstitium between the genioglossus and hyoglossus muscles, the branches of the lingual nerve (LN) and the medial trunk of the hypoglossal nerve (HN) had a layered disposition of the outer and inner side, respectively, of the lingual artery with its periarterial plexus. Anastomoses of these three distinctive neural suppliers of tongue were recorded, as also were those of the LN with the lateral trunk of the HN and the anastomoses between successive terminal branches of the LN. Successive ansae linguales were joining the LN branches and the medial trunk of the HN. The intrinsic neural system of the tongue supports integrative functions and allows a better retrospective understanding of various experimental studies. The topographical pattern is useful for an accurate diagnosis of intralingual nerves on microscopic slides.

Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain.

PubMed

Groppe, Sarah E; Gossen, Anna; Rademacher, Lena; Hahn, Alexa; Westphal, Luzie; Gründer, Gerhard; Spreckelmeyer, Katja N

2013-08-01

Evidence accumulates that the neuropeptide oxytocin plays an important role in mediating social interaction among humans and that a dysfunction in oxytocin-modulated brain mechanisms might lie at the core of disturbed social behavior in neuropsychiatric disease. Explanatory models suggest that oxytocin guides social approach and avoidance by modulating the perceived salience of socially meaningful cues. Animal data point toward the ventral tegmental area (VTA) as the brain site where this modulation takes place. We used functional magnetic resonance imaging and a social incentive delay task to test the hypothesis that oxytocin modulates the neural processing of socially relevant cues in the VTA, hereby facilitating behavioral response. Twenty-eight nulliparous women (not taking any hormones) received intranasal oxytocin or placebo in a double-blind randomized clinical trial with a parallel-group design. Oxytocin significantly enhanced VTA activation in response to cues signaling social reward (friendly face) or social punishment (angry face). Oxytocin effects on behavioral performance were modulated by individual differences in sociability with enhanced performance in women scoring low but decreased performance in women scoring high on self-reported measures of agreeableness. Our data provide evidence that the VTA is the human brain site where oxytocin attaches salience to socially relevant cues. This mechanism might play an important role in triggering motivation to react at the prospect of social reward or punishment. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Associating a product with a luxury brand label modulates neural reward processing and favors choices in materialistic individuals.

PubMed

Audrin, Catherine; Ceravolo, Leonardo; Chanal, Julien; Brosch, Tobias; Sander, David

2017-11-23

The present study investigated the extent to which luxury vs. non-luxury brand labels (i.e., extrinsic cues) randomly assigned to items and preferences for these items impact choice, and how this impact may be moderated by materialistic tendencies (i.e., individual characteristics). The main objective was to investigate the neural correlates of abovementioned effects using functional magnetic resonance imaging. Behavioural results showed that the more materialistic people are, the more they choose and like items labelled with luxury brands. Neuroimaging results revealed the implication of a neural network including the dorsolateral and ventromedial prefrontal cortex and the orbitofrontal cortex that was modulated by the brand label and also by the participants' preference. Most importantly, items with randomly assigned luxurious brand labels were preferentially chosen by participants and triggered enhanced signal in the caudate nucleus. This effect increased linearly with materialistic tendencies. Our results highlight the impact of brand-item association, although random in our study, and materialism on preference, relying on subparts of the brain valuation system for the integration of extrinsic cues, preferences and individual characteristics.

Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells.

PubMed

Sugiyama-Nakagiri, Yoriko; Fujimura, Tsutomu; Moriwaki, Shigeru

2016-01-01

The generation of full thickness human skin from dissociated cells is an attractive approach not only for treating skin diseases, but also for treating many systemic disorders. However, it is currently not possible to obtain an unlimited number of skin dermal cells. The goal of this study was to develop a procedure to produce skin dermal stem cells from induced pluripotent stem cells (iPSCs). Skin-derived precursor cells (SKPs) were isolated as adult dermal precursors that could differentiate into both neural and mesodermal progenies and could reconstitute the dermis. Thus, we attempted to generate SKPs from iPSCs that could reconstitute the skin dermis. Human iPSCs were initially cultured with recombinant noggin and SB431542, an inhibitor of activin/nodal and TGFβ signaling, to induce neural crest progenitor cells. Those cells were then treated with SKP medium that included CHIR99021, a WNT signal activator. The induction efficacy from neural crest progenitor cells to SKPs was more than 97%. No other modifiers tested were able to induce those cells. Those human iPSC-derived SKPs (hiPSC-SKPs) showed a similar gene expression signature to SKPs isolated from human skin dermis. Human iPSC-SKPs differentiated into neural and mesodermal progenies, including adipocytes, skeletogenic cell types and Schwann cells. Moreover, they could be induced to follicular type keratinization when co-cultured with human epidermal keratinocytes. We here provide a new efficient protocol to create human skin dermal stem cells from hiPSCs that could contribute to the treatment of various skin disorders.

3D culture models of Alzheimer's disease: a road map to a "cure-in-a-dish".

PubMed

Choi, Se Hoon; Kim, Young Hye; Quinti, Luisa; Tanzi, Rudolph E; Kim, Doo Yeon

2016-12-09

Alzheimer's disease (AD) transgenic mice have been used as a standard AD model for basic mechanistic studies and drug discovery. These mouse models showed symbolic AD pathologies including β-amyloid (Aβ) plaques, gliosis and memory deficits but failed to fully recapitulate AD pathogenic cascades including robust phospho tau (p-tau) accumulation, clear neurofibrillary tangles (NFTs) and neurodegeneration, solely driven by familial AD (FAD) mutation(s). Recent advances in human stem cell and three-dimensional (3D) culture technologies made it possible to generate novel 3D neural cell culture models that recapitulate AD pathologies including robust Aβ deposition and Aβ-driven NFT-like tau pathology. These new 3D human cell culture models of AD hold a promise for a novel platform that can be used for mechanism studies in human brain-like environment and high-throughput drug screening (HTS). In this review, we will summarize the current progress in recapitulating AD pathogenic cascades in human neural cell culture models using AD patient-derived induced pluripotent stem cells (iPSCs) or genetically modified human stem cell lines. We will also explain how new 3D culture technologies were applied to accelerate Aβ and p-tau pathologies in human neural cell cultures, as compared the standard two-dimensional (2D) culture conditions. Finally, we will discuss a potential impact of the human 3D human neural cell culture models on the AD drug-development process. These revolutionary 3D culture models of AD will contribute to accelerate the discovery of novel AD drugs.

Making an Effort to Feel Positive: Insecure Attachment in Infancy Predicts the Neural Underpinnings of Emotion Regulation in Adulthood

ERIC Educational Resources Information Center

Moutsiana, Christina; Fearon, Pasco; Murray, Lynne; Cooper, Peter; Goodyer, Ian; Johnstone, Tom; Halligan, Sarah

2014-01-01

Background: Animal research indicates that the neural substrates of emotion regulation may be persistently altered by early environmental exposures. If similar processes operate in human development then this is significant, as the capacity to regulate emotional states is fundamental to human adaptation. Methods: We utilised a 22-year longitudinal…

Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures.

PubMed

Knight, V Bleu; Serrano, Elba E

2017-01-01

Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro . Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA) cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue.

Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation.

PubMed

Sameiro-Barbosa, Catia M; Geiser, Eveline

2016-01-01

The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system.

A trigger-based design for evaluating the safety of in utero antiretroviral exposure in uninfected children of human immunodeficiency virus-infected mothers.

PubMed

Williams, Paige L; Seage, George R; Van Dyke, Russell B; Siberry, George K; Griner, Raymond; Tassiopoulos, Katherine; Yildirim, Cenk; Read, Jennifer S; Huo, Yanling; Hazra, Rohan; Jacobson, Denise L; Mofenson, Lynne M; Rich, Kenneth

2012-05-01

The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a "trigger-based" design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or "triggers" undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios.

SnapShot: Hormones of the gastrointestinal tract.

PubMed

Coate, Katie C; Kliewer, Steven A; Mangelsdorf, David J

2014-12-04

Specialized endocrine cells secrete a variety of peptide hormones all along the gastrointestinal (GI) tract, making it one of the largest endocrine organs in the body. Nutrients and developmental and neural cues trigger the secretion of gastrointestinal (GI) hormones from specialized endocrine cells along the GI tract. These hormones act in target tissues to facilitate digestion and regulate energy homeostasis. This SnapShot summarizes the production and functions of GI hormones. Copyright © 2014 Elsevier Inc. All rights reserved.

Improving Robot Motor Learning with Negatively Valenced Reinforcement Signals

PubMed Central

Navarro-Guerrero, Nicolás; Lowe, Robert J.; Wermter, Stefan

2017-01-01

Both nociception and punishment signals have been used in robotics. However, the potential for using these negatively valenced types of reinforcement learning signals for robot learning has not been exploited in detail yet. Nociceptive signals are primarily used as triggers of preprogrammed action sequences. Punishment signals are typically disembodied, i.e., with no or little relation to the agent-intrinsic limitations, and they are often used to impose behavioral constraints. Here, we provide an alternative approach for nociceptive signals as drivers of learning rather than simple triggers of preprogrammed behavior. Explicitly, we use nociception to expand the state space while we use punishment as a negative reinforcement learning signal. We compare the performance—in terms of task error, the amount of perceived nociception, and length of learned action sequences—of different neural networks imbued with punishment-based reinforcement signals for inverse kinematic learning. We contrast the performance of a version of the neural network that receives nociceptive inputs to that without such a process. Furthermore, we provide evidence that nociception can improve learning—making the algorithm more robust against network initializations—as well as behavioral performance by reducing the task error, perceived nociception, and length of learned action sequences. Moreover, we provide evidence that punishment, at least as typically used within reinforcement learning applications, may be detrimental in all relevant metrics. PMID:28420976

Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array

NASA Astrophysics Data System (ADS)

Simeral, J. D.; Kim, S.-P.; Black, M. J.; Donoghue, J. P.; Hochberg, L. R.

2011-04-01

The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point-and-click control of a computer interface to an individual with tetraplegia 1000 days after implantation of this sensor.

Neural control of cursor trajectory and click by a human with tetraplegia 1000 days after implant of an intracortical microelectrode array

PubMed Central

Simeral, J D; Kim, S-P; Black, M J; Donoghue, J P; Hochberg, L R

2013-01-01

The ongoing pilot clinical trial of the BrainGate neural interface system aims in part to assess the feasibility of using neural activity obtained from a small-scale, chronically implanted, intracortical microelectrode array to provide control signals for a neural prosthesis system. Critical questions include how long implanted microelectrodes will record useful neural signals, how reliably those signals can be acquired and decoded, and how effectively they can be used to control various assistive technologies such as computers and robotic assistive devices, or to enable functional electrical stimulation of paralyzed muscles. Here we examined these questions by assessing neural cursor control and BrainGate system characteristics on five consecutive days 1000 days after implant of a 4 × 4 mm array of 100 microelectrodes in the motor cortex of a human with longstanding tetraplegia subsequent to a brainstem stroke. On each of five prospectively-selected days we performed time-amplitude sorting of neuronal spiking activity, trained a population-based Kalman velocity decoding filter combined with a linear discriminant click state classifier, and then assessed closed-loop point-and-click cursor control. The participant performed both an eight-target center-out task and a random target Fitts metric task which was adapted from a human-computer interaction ISO standard used to quantify performance of computer input devices. The neural interface system was further characterized by daily measurement of electrode impedances, unit waveforms and local field potentials. Across the five days, spiking signals were obtained from 41 of 96 electrodes and were successfully decoded to provide neural cursor point-and-click control with a mean task performance of 91.3% ± 0.1% (mean ± s.d.) correct target acquisition. Results across five consecutive days demonstrate that a neural interface system based on an intracortical microelectrode array can provide repeatable, accurate point-and-click control of a computer interface to an individual with tetraplegia 1000 days after implantation of this sensor. PMID:21436513

Functional Roles of Neural Preparatory Processes in a Cued Stroop Task Revealed by Linking Electrophysiology with Behavioral Performance

PubMed Central

Wang, Chao; Ding, Mingzhou; Kluger, Benzi M.

2015-01-01

It is well established that cuing facilitates behavioral performance and that different aspects of instructional cues evoke specific neural preparatory processes in cued task-switching paradigms. To deduce the functional role of these neural preparatory processes the majority of studies vary aspects of the experimental paradigm and describe how these variations alter markers of neural preparatory processes. Although these studies provide important insights, they also have notable limitations, particularly in terms of understanding the causal or functional relationship of neural markers to cognitive and behavioral processes. In this study, we sought to address these limitations and uncover the functional roles of neural processes by examining how variability in the amplitude of neural preparatory processes predicts behavioral performance to subsequent stimuli. To achieve this objective 16 young adults were recruited to perform a cued Stroop task while their brain activity was measured using high-density electroencephalography. Four temporally overlapping but functionally and topographically distinct cue-triggered event related potentials (ERPs) were identified: 1) A left-frontotemporal negativity (250-700 ms) that was positively associated with word-reading performance; 2) a midline-frontal negativity (450-800 ms) that was positively associated with color-naming and incongruent performance; 3) a left-frontal negativity (450-800 ms) that was positively associated with switch trial performance; and 4) a centroparietal positivity (450-800 ms) that was positively associated with performance for almost all trial types. These results suggest that at least four dissociable cognitive processes are evoked by instructional cues in the present task, including: 1) domain-specific task facilitation; 2) switch-specific task-set reconfiguration; 3) preparation for response conflict; and 4) proactive attentional control. Examining the relationship between ERPs and behavioral performance provides a functional link between neural markers and the cognitive processes they index. PMID:26230662

Human and animal cognition: Continuity and discontinuity

PubMed Central

Premack, David

2007-01-01

Microscopic study of the human brain has revealed neural structures, enhanced wiring, and forms of connectivity among nerve cells not found in any animal, challenging the view that the human brain is simply an enlarged chimpanzee brain. On the other hand, cognitive studies have found animals to have abilities once thought unique to the human. This suggests a disparity between brain and mind. The suggestion is misleading. Cognitive research has not kept pace with neural research. Neural findings are based on microscopic study of the brain and are primarily cellular. Because cognition cannot be studied microscopically, we need to refine the study of cognition by using a different approach. In examining claims of similarity between animals and humans, one must ask: What are the dissimilarities? This approach prevents confusing similarity with equivalence. We follow this approach in examining eight cognitive cases—teaching, short-term memory, causal reasoning, planning, deception, transitive inference, theory of mind, and language—and find, in all cases, that similarities between animal and human abilities are small, dissimilarities large. There is no disparity between brain and mind. PMID:17717081

Faith-based perspectives on the use of chimeric organisms for medical research.

PubMed

Degeling, Chris; Irvine, Rob; Kerridge, Ian

2014-04-01

Efforts to advance our understanding of neurodegenerative diseases involve the creation chimeric organisms from human neural stem cells and primate embryos--known as prenatal chimeras. The existence of potential mentally complex beings with human and non-human neural apparatus raises fundamental questions as to the ethical permissibility of chimeric research and the moral status of the creatures it creates. Even as bioethicists find fewer reasons to be troubled by most types of chimeric organisms, social attitudes towards the non-human world are often influenced by religious beliefs. In this paper scholars representing eight major religious traditions provide a brief commentary on a hypothetical case concerning the development and use of prenatal human-animal chimeric primates in medical research. These commentaries reflect the plurality and complexity within and between religious discourses of our relationships with other species. Views on the moral status and permissibility of research on neural human animal chimeras vary. The authors provide an introduction to those who seek a better understanding of how faith-based perspectives might enter into biomedical ethics and public discourse towards forms of biomedical research that involves chimeric organisms.

Emotion-induced trade-offs in spatiotemporal vision.

PubMed

Bocanegra, Bruno R; Zeelenberg, René

2011-05-01

It is generally assumed that emotion facilitates human vision in order to promote adaptive responses to a potential threat in the environment. Surprisingly, we recently found that emotion in some cases impairs the perception of elementary visual features (Bocanegra & Zeelenberg, 2009b). Here, we demonstrate that emotion improves fast temporal vision at the expense of fine-grained spatial vision. We tested participants' threshold resolution with Landolt circles containing a small spatial or brief temporal discontinuity. The prior presentation of a fearful face cue, compared with a neutral face cue, impaired spatial resolution but improved temporal resolution. In addition, we show that these benefits and deficits were triggered selectively by the global configural properties of the faces, which were transmitted only through low spatial frequencies. Critically, the common locus of these opposite effects suggests a trade-off between magno- and parvocellular-type visual channels, which contradicts the common assumption that emotion invariably improves vision. We show that, rather than being a general "boost" for all visual features, affective neural circuits sacrifice the slower processing of small details for a coarser but faster visual signal.

Modulatory Mechanism of Polyphenols and Nrf2 Signaling Pathway in LPS Challenged Pregnancy Disorders

PubMed Central

Murtaza, Ghulam; Rahu, Najma; Saleem, Muhammad

2017-01-01

Early embryonic loss and adverse birth outcomes are the major reproductive disorders that affect both human and animals. The LPS induces inflammation by interacting with robust cellular mechanism which was considered as a plethora of numerous reproductive disorders such as fetal resorption, preterm birth, teratogenicity, intrauterine growth restriction, abortion, neural tube defects, fetal demise, and skeletal development retardation. LPS-triggered overproduction of free radicals leads to oxidative stress which mediates inflammation via stimulation of NF-κB and PPARγ transcription factors. Flavonoids, which exist in copious amounts in nature, possess a wide array of functions; their supplementation during pregnancy activates Nrf2 signaling pathway which encounters pregnancy disorders. It was further presumed that the development of strong antioxidant uterine environment during gestation can alleviate diseases which appear at adult stages. The purpose of this review is to focus on modulatory properties of flavonoids on oxidative stress-mediated pregnancy insult and abnormal outcomes and role of Nrf2 activation in pregnancy disorders. These findings would be helpful for providing new insights in ameliorating oxidative stress-induced pregnancy disorders. PMID:29138679

Acquisition of Joint Attention by a Developmental Learning Model based on Interactions between a Robot and a Caregiver

NASA Astrophysics Data System (ADS)

Nagai, Yukie; Asada, Minoru; Hosoda, Koh

This paper presents a developmental learning model for joint attention between a robot and a human caregiver. The basic idea of the proposed model comes from the insight of the cognitive developmental science that the development can help the task learning. The model consists of a learning mechanism based on evaluation and two kinds of developmental mechanisms: a robot's development and a caregiver's one. The former means that the sensing and the actuating capabilities of the robot change from immaturity to maturity. On the other hand, the latter is defined as a process that the caregiver changes the task from easy situation to difficult one. These two developments are triggered by the learning progress. The experimental results show that the proposed model can accelerate the learning of joint attention owing to the caregiver's development. Furthermore, it is observed that the robot's development can improve the final task performance by reducing the internal representation in the learned neural network. The mechanisms that bring these effects to the learning are analyzed in line with the cognitive developmental science.

Probiotics drive gut microbiome triggering emotional brain signatures.

PubMed

Bagga, Deepika; Reichert, Johanna Louise; Koschutnig, Karl; Aigner, Christoph Stefan; Holzer, Peter; Koskinen, Kaisa; Eichinger, Christine Moissl; Schöpf, Veronika

2018-05-03

Experimental manipulation of the gut microbiome was found to modify emotional and cognitive behavior, neurotransmitter expression and brain function in rodents, but corresponding human data remain scarce. The present double-blind, placebo-controlled randomised study aimed at investigating the effects of 4 weeks' probiotic administration on behavior, brain function and gut microbial composition in healthy volunteers. Forty-five healthy participants divided equally into three groups (probiotic, placebo and no intervention) underwent functional MRI (emotional decision-making and emotional recognition memory tasks). In addition, stool samples were collected to investigate the gut microbial composition. Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks, which were also accompanied by subtle shifts in gut microbiome profile. Microbiome composition mirrored self-reported behavioral measures and memory performance. This is the first study reporting a distinct influence of probiotic administration at behavioral, neural, and microbiome levels at the same time in healthy volunteers. The findings provide a basis for future investigations into the role of the gut microbiota and potential therapeutic application of probiotics.

Strategic modulation of cognitive control.

PubMed

Lungu, Ovidiu V; Liu, Tao; Waechter, Tobias; Willingham, Daniel T; Ashe, James

2007-08-01

The neural substrate of cognitive control is thought to comprise an evaluative component located in the anterior cingulate cortex (ACC) and an executive component in the prefrontal cortex (PFC). The control mechanism itself is mainly local, triggered by response conflict (monitored by the ACC) and involving the allocation of executive resources (recruited by the PFC) in a trial-to-trial fashion. However, another way to achieve control would be to use a strategic mechanism based on long-term prediction of upcoming events and on a chronic response strategy that ignores local features of the task. In the current study, we showed that such a strategic control mechanism was based on a functional dissociation or complementary relationship between the ACC and the PFC. When information in the environment was available to make predictions about upcoming stimuli, local task features (e.g., response conflict) were no longer used as a control signal. We suggest that having separate control mechanisms based on local or global task features allows humans to be persistent in pursuing their goals, yet flexible enough to adapt to changes in the environment.

The effects of curcumin on proliferation, apoptosis, invasion, and NEDD4 expression in pancreatic cancer.

PubMed

Su, Jingna; Zhou, Xiuxia; Yin, Xuyuan; Wang, Lixia; Zhao, Zhe; Hou, Yingying; Zheng, Nana; Xia, Jun; Wang, Zhiwei

2017-09-15

Pancreatic cancer (PC) is one of the most fatal cancers worldwide. The incidence and death rates are still increasing for PC. Curcumin is the biologically active diarylheptanoid constituent of the spice turmeric, which exerts its anticancer properties in various human cancers including PC. In particular, accumulating evidence has proved that curcumin targets numerous therapeutically important proteins in cell signaling pathways. The neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 HECT ubiquitin ligase and is frequently over-expressed in various cancers. It has reported that NEDD4 might facilitate tumorigenesis via targeting and degradation of multiple tumor suppressor proteins including PTEN. Hence, in the present study we explore whether curcumin inhibits NEDD4, resulting in the suppression of cell growth, migration and invasion in PC cells. We found that curcumin inhibited cell proliferation and triggered apoptosis in PC, which is associated with increased expression of PTEN and p73. These results suggested that inhibition of NEDD4 might be beneficial to the antitumor properties of curcumin on PC treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Thoughts of Death Modulate Psychophysical and Cortical Responses to Threatening Stimuli

PubMed Central

Valentini, Elia; Koch, Katharina; Aglioti, Salvatore Maria

2014-01-01

Existential social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Therefore we explored whether reminders of mortality influence subjective ratings of intensity and threat of auditory and painful thermal stimuli and the associated electroencephalographic activity. Moreover, we explored whether personality and demographics modulate psychophysical and neural changes related to mortality salience (MS). Following MS induction, a specific increase in ratings of intensity and threat was found for both nociceptive and auditory stimuli. While MS did not have any specific effect on nociceptive and auditory evoked potentials, larger amplitude of theta oscillatory activity related to thermal nociceptive activity was found after thoughts of death were induced. MS thus exerted a top-down modulation on theta electroencephalographic oscillatory amplitude, specifically for brain activity triggered by painful thermal stimuli. This effect was higher in participants reporting higher threat perception, suggesting that inducing a death-related mind-set may have an influence on body-defence related somatosensory representations. PMID:25386905

Physiological and environmental control of yeast prions

PubMed Central

Chernova, Tatiana A.; Wilkinson, Keith D.; Chernoff, Yury O.

2014-01-01

Prions are self-perpetuating protein isoforms that cause fatal and incurable neurodegenerative disease in mammals. Recent evidence indicates that a majority of human proteins involved in amyloid and neural inclusion disorders possess at least some prion properties. In lower eukaryotes, such as yeast, prions act as epigenetic elements, which increase phenotypic diversity by altering a range of cellular processes. While some yeast prions are clearly pathogenic, it is also postulated that prion formation could be beneficial in variable environmental conditions. Yeast and mammalian prions have similar molecular properties. Crucial cellular factors and conditions influencing prion formation and propagation were uncovered in the yeast models. Stress-related chaperones, protein quality control deposits, degradation pathways and cytoskeletal networks control prion formation and propagation in yeast. Environmental stresses trigger prion formation and loss, supposedly acting via influencing intracellular concentrations of the prion-inducing proteins, and/or by localizing prionogenic proteins to the prion induction sites via heterologous ancillary helpers. Physiological and environmental modulation of yeast prions points to new opportunities for pharmacological intervention and/or prophylactic measures targeting general cellular systems rather than the properties of individual amyloids and prions. PMID:24236638

Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception

NASA Astrophysics Data System (ADS)

Muller, Leah; Rolston, John D.; Fox, Neal P.; Knowlton, Robert; Rao, Vikram R.; Chang, Edward F.

2018-04-01

Objective. Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. Approach. To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. Main results. We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. Significance. Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.

Decoding Spontaneous Emotional States in the Human Brain

PubMed Central

Kragel, Philip A.; Knodt, Annchen R.; Hariri, Ahmad R.; LaBar, Kevin S.

2016-01-01

Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states. These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction procedures. Here we assess whether neural models developed to discriminate among distinct emotion categories exhibit predictive validity in the absence of exteroceptive emotional stimulation. In two experiments, we show that spontaneous fluctuations in human resting-state brain activity can be decoded into categories of experience delineating unique emotional states that exhibit spatiotemporal coherence, covary with individual differences in mood and personality traits, and predict on-line, self-reported feelings. These findings validate objective, brain-based models of emotion and show how emotional states dynamically emerge from the activity of separable neural systems. PMID:27627738

Scary symptoms? Functional magnetic resonance imaging evidence for symptom interpretation bias in pathological health anxiety.

PubMed

Yan, Zhimin; Witthöft, Michael; Bailer, Josef; Diener, Carsten; Mier, Daniela

2017-08-12

Patients with pathological health anxiety (PHA) tend to automatically interpret bodily sensations as sign of a severe illness. To elucidate the neural correlates of this cognitive bias, we applied an functional magnetic resonance imaging adaption of a body-symptom implicit association test with symptom words in patients with PHA (n = 32) in comparison to patients with depression (n = 29) and healthy participants (n = 35). On the behavioral level, patients with PHA did not significantly differ from the control groups. However, on the neural-level patients with PHA in comparison to the control groups showed hyperactivation independent of condition in bilateral amygdala, right parietal lobe, and left nucleus accumbens. Moreover, patients with PHA, again in comparison to the control groups, showed hyperactivation in bilateral posterior parietal cortex and left dorsolateral prefrontal cortex during incongruent (i.e., harmless) versus congruent (i.e., dangerous) categorizations of body symptoms. Thus, body-symptom cues seem to trigger hyperactivity in salience and emotion processing brain regions in PHA. In addition, hyperactivity in brain regions involved in cognitive control and conflict resolution during incongruent categorization emphasizes enhanced neural effort to cope with negative implicit associations to body-symptom-related information in PHA. These results suggest increased neural responding in key structures for the processing of both emotional and cognitive aspects of body-symptom information in PHA, reflecting potential neural correlates of a negative somatic symptom interpretation bias.

Short-wavelength infrared laser activates the auditory neurons: comparing the effect of 980 vs. 810 nm wavelength.

PubMed

Tian, Lan; Wang, Jingxuan; Wei, Ying; Lu, Jianren; Xu, Anting; Xia, Ming

2017-02-01

Research on auditory neural triggering by optical stimulus has been developed as an emerging technique to elicit the auditory neural response, which may provide an alternative method to the cochlear implants. However, most previous studies have been focused on using longer-wavelength near-infrared (>1800 nm) laser. The effect comparison of different laser wavelengths in short-wavelength infrared (SWIR) range on the auditory neural stimulation has not been previously explored. In this study, the pulsed 980- and 810-nm SWIR lasers were applied as optical stimuli to irradiate the auditory neurons in the cochlea of five deafened guinea pigs and the neural response under the two laser wavelengths was compared by recording the evoked optical auditory brainstem responses (OABRs). In addition, the effect of radiant exposure, laser pulse width, and threshold with the two laser wavelengths was further investigated and compared. The one-way analysis of variance (ANOVA) was used to analyze those data. Results showed that the OABR amplitude with the 980-nm laser is higher than the amplitude with the 810-nm laser under the same radiant exposure from 10 to 102 mJ/cm 2 . And the laser stimulation of 980 nm wavelength has lower threshold radiant exposure than the 810 nm wavelength at varied pulse duration in 20-500 μs range. Moreover, the 810-nm laser has a wider optimized pulse duration range than the 980-nm laser for the auditory neural stimulation.

A fully-automated neural network analysis of AFM force-distance curves for cancer tissue diagnosis

NASA Astrophysics Data System (ADS)

Minelli, Eleonora; Ciasca, Gabriele; Sassun, Tanya Enny; Antonelli, Manila; Palmieri, Valentina; Papi, Massimiliano; Maulucci, Giuseppe; Santoro, Antonio; Giangaspero, Felice; Delfini, Roberto; Campi, Gaetano; De Spirito, Marco

2017-10-01

Atomic Force Microscopy (AFM) has the unique capability of probing the nanoscale mechanical properties of biological systems that affect and are affected by the occurrence of many pathologies, including cancer. This capability has triggered growing interest in the translational process of AFM from physics laboratories to clinical practice. A factor still hindering the current use of AFM in diagnostics is related to the complexity of AFM data analysis, which is time-consuming and needs highly specialized personnel with a strong physical and mathematical background. In this work, we demonstrate an operator-independent neural-network approach for the analysis of surgically removed brain cancer tissues. This approach allowed us to distinguish—in a fully automated fashion—cancer from healthy tissues with high accuracy, also highlighting the presence and the location of infiltrating tumor cells.

A novel, immortal, and multipotent human neural stem cell line generating functional neurons and oligodendrocytes.

PubMed

De Filippis, Lidia; Lamorte, Giuseppe; Snyder, Evan Y; Malgaroli, Antonio; Vescovi, Angelo L

2007-09-01

The discovery and study of neural stem cells have revolutionized our understanding of the neurogenetic process, and their inherent ability to adopt expansive growth behavior in vitro is of paramount importance for the development of novel therapeutics based on neural cell replacement. Recent advances in high-throughput assays for drug development and gene discovery dictate the need for rapid, reproducible, long-term expansion of human neural stem cells (hNSCs). In this view, the complement of wild-type cell lines currently available is insufficient. Here we report the establishment of a stable human neural stem cell line (immortalized human NSCs [IhNSCs]) by v-myc-mediated immortalization of previously derived wild-type hNSCs. These cells demonstrate three- to fourfold faster proliferation than wild-type cells in response to growth factors but retain rather similar properties, including multipotentiality. By molecular biology, biochemistry, immunocytochemistry, fluorescence microscopy, and electrophysiology, we show that upon growth factor removal, IhNSCs completely downregulate v-myc expression, cease proliferation, and differentiate terminally into three major neural lineages: astrocytes, oligodendrocytes, and neurons. The latter are functional, mature cells displaying clear-cut morphological and physiological features of terminally differentiated neurons, encompassing mostly the GABAergic, glutamatergic, and cholinergic phenotypes. Finally, IhNSCs produce bona fide oligodendrocytes in fractions up to 20% of total cell number. This is in contrast to the negligible propensity of hNSCs to generate oligodendroglia reported so far. Thus, we describe an immortalized hNSC line endowed with the properties of normal hNSCs and suitable for developing the novel, reliable assays and reproducible high-throughput gene and drug screening that are essential in both diagnostics and cell therapy studies.

The human body odor compound androstadienone increases neural conflict coupled to higher behavioral costs during an emotional Stroop task.

PubMed

Hornung, Jonas; Kogler, Lydia; Erb, Michael; Freiherr, Jessica; Derntl, Birgit

2018-05-01

The androgen derivative androstadienone (AND) is a substance found in human sweat and thus may act as human chemosignal. With the current experiment, we aimed to explore in which way AND affects interference processing during an emotional Stroop task which used human faces as target and emotional words as distractor stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to unravel the neural mechanism of AND-action. Based on previous accounts we expected AND to increase neural activation in areas commonly implicated in evaluation of emotional face processing and to change neural activation in brain regions linked to interference processing. For this aim, a total of 80 healthy individuals (oral contraceptive users, luteal women, men) were tested twice on two consecutive days with an emotional Stroop task using fMRI. Our results suggest that AND increases interference processing in brain areas that are heavily recruited during emotional conflict. At the same time, correlation analyses revealed that this neural interference processing was paralleled by higher behavioral costs (response times) with higher interference related brain activation under AND. Furthermore, AND elicited higher activation in regions implicated in emotional face processing including right fusiform gyrus, inferior frontal gyrus and dorsomedial cortex. In this connection, neural activation was not coupled to behavioral outcome. Furthermore, despite previous accounts of increased hypothalamic activation under AND, we were not able to replicate this finding and discuss possible reasons for this discrepancy. To conclude, AND increased interference processing in regions heavily recruited during emotional conflict which was coupled to higher costs in resolving emotional conflicts with stronger interference-related brain activation under AND. At the moment it remains unclear whether these effects are due to changes in conflict detection or resolution. However, evidence most consistently suggests that AND does not draw attention to the most potent socio-emotional information (human faces) but rather highlights representations of emotional words. Copyright © 2018 Elsevier Inc. All rights reserved.

Neural correlate of human reciprocity in social interactions

PubMed Central

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. PMID:24381534

Neural correlate of human reciprocity in social interactions.

PubMed

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.

Neural Networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Patrick I.

2003-09-23

Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neuralmore » networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing information [2]. Each one of these cells acts as a simple processor. When individual cells interact with one another, the complex abilities of the brain are made possible. In neural networks, the input or data are processed by a propagation function that adds up the values of all the incoming data. The ending value is then compared with a threshold or specific value. The resulting value must exceed the activation function value in order to become output. The activation function is a mathematical function that a neuron uses to produce an output referring to its input value. [8] Figure 1 depicts this process. Neural networks usually have three components an input, a hidden, and an output. These layers create the end result of the neural network. A real world example is a child associating the word dog with a picture. The child says dog and simultaneously looks a picture of a dog. The input is the spoken word ''dog'', the hidden is the brain processing, and the output will be the category of the word dog based on the picture. This illustration describes how a neural network functions.« less

Investigation of index finger triggering force using a cadaver experiment: Effects of trigger grip span, contact location, and internal tendon force.

PubMed

Chang, Joonho; Freivalds, Andris; Sharkey, Neil A; Kong, Yong-Ku; Mike Kim, H; Sung, Kiseok; Kim, Dae-Min; Jung, Kihyo

2017-11-01

A cadaver study was conducted to investigate the effects of triggering conditions (trigger grip span, contact location, and internal tendon force) on index finger triggering force and the force efficiency of involved tendons. Eight right human cadaveric hands were employed, and a motion simulator was built to secure and control the specimens. Index finger triggering forces were investigated as a function of different internal tendon forces (flexor digitorum profundus + flexor digitorum superficialis = 40, 70, and 100 N), trigger grip spans (40, 50, and 60 mm), and contact locations between the index finger and a trigger. Triggering forces significantly increased when internal tendon forces increased from 40 to 100 N. Also, trigger grip spans and contact locations had significant effects on triggering forces; maximum triggering forces were found at a 50 mm span and the most proximal contact location. The results revealed that only 10-30% of internal tendon forces were converted to their external triggering forces. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

PubMed

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 different neuronal subtypes in 3-D differentiation from hiPSCs and the differential cellular responses of region-specific neuronal subtypes to various biomolecules have not been fully investigated. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog signaling, this study provides knowledge on the differential susceptibility of region-specific neuronal subtypes derived from hiPSCs to different biomolecules in extracellular matrix remodeling and neurotoxicity. The findings are significant for understanding 3-D neural patterning of hiPSCs for the applications in brain organoid formation, neurological disease modeling, and drug discovery. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development

PubMed Central

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L.; Baserga, Susan; Yelick, Pamela C.

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome. PMID:24497835

Inhibition of Neurogenesis by Zika virus Infection.

PubMed

Ahmad, Fahim; Siddiqui, Amna; Kamal, Mohammad A; Sohrab, Sayed S

2018-02-01

The association between Zika virus infection and neurological disorder has raised urgent global alarm. The ongoing epidemic has triggered quick responses in the scientific community. The first case of Zika virus was reported in 2015 from Brazil and now has spread over 30 countries. Nearly four hundred cases of travel-associated Zika virus infection have also been reported in the United States. Zika virus is primarily transmitted by mosquito belongs to the genus Aedes that are widely distributed throughout the world including the Southern United States. Additionally, the virus can also be transmitted from males to females by sexual contact. The epidemiological investigations during the current outbreak found a causal link between infection in pregnant women and development of microcephaly in their unborn babies. This finding is a cause for grave concern since microcephaly is a serious neural developmental disorder that can lead to significant post-natal developmental abnormalities and disabilities. Recently, published data indicate that Zika virus infection affects the growth of fetal neural progenitor cells and cerebral neurons that results in malformation of cerebral cortex leading to microcephaly. Recently, it has been reported that Zika virus infection deregulates the signaling pathway of neuronal cell and inhibit the neurogenesis resulting into dementia. In this review we have discussed about the information about cellular and molecular mechanisms in neurodegeneration of human neuronal cells and inhibit the neurogenesis. Additionally, this information will be very helpful further not only in neuro-scientific research but also designing and development of management strategies for microcephaly and other mosquito borne disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neural Circuitry of the Bilingual Mental Lexicon: Effect of Age of Second Language Acquisition

ERIC Educational Resources Information Center

Isel, Frederic; Baumgaertner, Annette; Thran, Johannes; Meisel, Jurgen M.; Buchel, Christian

2010-01-01

Numerous studies have proposed that changes of the human language faculty caused by neural maturation can explain the substantial differences in ultimate attainment of grammatical competences between first language (L1) acquirers and second language (L2) learners. However, little evidence on the effect of neural maturation on the attainment of…

Generation of H1 PAX6WT/EGFP reporter cells to purify PAX6 positive neural stem/progenitor cells.

PubMed

Wu, Wei; Liu, Juli; Su, Zhenghui; Li, Zhonghao; Ma, Ning; Huang, Ke; Zhou, Tiancheng; Wang, Linli

2018-08-25

Neural conversion from human pluripotent cells (hPSCs) is a potential therapy to neurological disease in the future. However, this is still limited by efficiency and stability of existed protocols used for neural induction from hPSCs. To overcome this obstacle, we developed a reporter system to screen PAX6 + neural progenitor/stem cells using transcription activator like effector nuclease (TALEN). We found that knock-in 2 A-EGFP cassette into PAX6 exon of human embryonic stem cells H1 with TALEN-based homology recombination could establish PAX6 WT/EGFP H1 reporter cell line fast and efficiently. This reporter cell line could differentiate into PAX6 and EGFP double positive neural progenitor/stem cells (NPCs/NSCs) after neural induction. Those PAX6 WT/EGFP NPCs could be purified, expanded and specified to post-mitotic neurons in vitro efficiently. With this reporter cell line, we also screened out 1 NPC-specific microRNA, hsa-miR-99a-5p, and 3 ESCs-enriched miRNAs, hsa-miR-302c-5p, hsa-miR-512-3p and hsa-miR-518 b. In conclusion, the TALEN-based neural stem cell screening system is safe and efficient and could help researcher to acquire adequate and pure neural progenitor cells for further application. Copyright © 2018 Elsevier Inc. All rights reserved.

Applying cybernetic technology to diagnose human pulmonary sounds.

PubMed

Chen, Mei-Yung; Chou, Cheng-Han

2014-06-01

Chest auscultation is a crucial and efficient method for diagnosing lung disease; however, it is a subjective process that relies on physician experience and the ability to differentiate between various sound patterns. Because the physiological signals composed of heart sounds and pulmonary sounds (PSs) are greater than 120 Hz and the human ear is not sensitive to low frequencies, successfully making diagnostic classifications is difficult. To solve this problem, we constructed various PS recognition systems for classifying six PS classes: vesicular breath sounds, bronchial breath sounds, tracheal breath sounds, crackles, wheezes, and stridor sounds. First, we used a piezoelectric microphone and data acquisition card to acquire PS signals and perform signal preprocessing. A wavelet transform was used for feature extraction, and the PS signals were decomposed into frequency subbands. Using a statistical method, we extracted 17 features that were used as the input vectors of a neural network. We proposed a 2-stage classifier combined with a back-propagation (BP) neural network and learning vector quantization (LVQ) neural network, which improves classification accuracy by using a haploid neural network. The receiver operating characteristic (ROC) curve verifies the high performance level of the neural network. To expand traditional auscultation methods, we constructed various PS diagnostic systems that can correctly classify the six common PSs. The proposed device overcomes the lack of human sensitivity to low-frequency sounds and various PS waves, characteristic values, and a spectral analysis charts are provided to elucidate the design of the human-machine interface.

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

PubMed

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.

Modification of existing human motor memories is enabled by primary cortical processing during memory reactivation.

PubMed

Censor, Nitzan; Dimyan, Michael A; Cohen, Leonardo G

2010-09-14

One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1-4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject's brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Human Central Pattern Generator for Locomotion.

PubMed

Minassian, Karen; Hofstoetter, Ursula S; Dzeladini, Florin; Guertin, Pierre A; Ijspeert, Auke

2017-03-01

The ability of dedicated spinal circuits, referred to as central pattern generators (CPGs), to produce the basic rhythm and neural activation patterns underlying locomotion can be demonstrated under specific experimental conditions in reduced animal preparations. The existence of CPGs in humans is a matter of debate. Equally elusive is the contribution of CPGs to normal bipedal locomotion. To address these points, we focus on human studies that utilized spinal cord stimulation or pharmacological neuromodulation to generate rhythmic activity in individuals with spinal cord injury, and on neuromechanical modeling of human locomotion. In the absence of volitional motor control and step-specific sensory feedback, the human lumbar spinal cord can produce rhythmic muscle activation patterns that closely resemble CPG-induced neural activity of the isolated animal spinal cord. In this sense, CPGs in humans can be defined by the activity they produce. During normal locomotion, CPGs could contribute to the activation patterns during specific phases of the step cycle and simplify supraspinal control of step cycle frequency as a feedforward component to achieve a targeted speed. Determining how the human CPGs operate will be essential to advance the theory of neural control of locomotion and develop new locomotor neurorehabilitation paradigms.

Relaxed genetic control of cortical organization in human brains compared with chimpanzees

PubMed Central

Gómez-Robles, Aida; Hopkins, William D.; Schapiro, Steven J.; Sherwood, Chet C.

2015-01-01

The study of hominin brain evolution has focused largely on the neocortical expansion and reorganization undergone by humans as inferred from the endocranial fossil record. Comparisons of modern human brains with those of chimpanzees provide an additional line of evidence to define key neural traits that have emerged in human evolution and that underlie our unique behavioral specializations. In an attempt to identify fundamental developmental differences, we have estimated the genetic bases of brain size and cortical organization in chimpanzees and humans by studying phenotypic similarities between individuals with known kinship relationships. We show that, although heritability for brain size and cortical organization is high in chimpanzees, cerebral cortical anatomy is substantially less genetically heritable than brain size in humans, indicating greater plasticity and increased environmental influence on neurodevelopment in our species. This relaxed genetic control on cortical organization is especially marked in association areas and likely is related to underlying microstructural changes in neural circuitry. A major result of increased plasticity is that the development of neural circuits that underlie behavior is shaped by the environmental, social, and cultural context more intensively in humans than in other primate species, thus providing an anatomical basis for behavioral and cognitive evolution. PMID:26627234

The Acoustic Trigger to Conceptualization: An Hypothesis Concerning the Role of the Spoken Word in the Development of Higher Mental Processes.

ERIC Educational Resources Information Center

Dance, Frank E. X.

One of many aspects of the linguistic centrality of the spoken word is the "acoustic trigger" to conceptualization, the most significant primal trigger in human beings, which when activated results in contrast and comparison leading to symbolic conceptualization. The oral/aural mode, or vocal production and acoustic perception, is developmentally…

Prolonged Expansion Induces Spontaneous Neural Progenitor Differentiation from Human Gingiva-Derived Mesenchymal Stem Cells.

PubMed

Rajan, Thangavelu Soundara; Scionti, Domenico; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

2017-12-01

Neural crest-derived mesenchymal stem cells (MSCs) obtained from dental tissues received considerable interest in regenerative medicine, particularly in nerve regeneration owing to their embryonic origin and ease of harvest. Proliferation efficacy and differentiation capacity into diverse cell lineages propose dental MSCs as an in vitro tool for disease modeling. In this study, we investigated the spontaneous differentiation efficiency of dental MSCs obtained from human gingiva tissue (hGMSCs) into neural progenitor cells after extended passaging. At passage 41, the morphology of hGMSCs changed from typical fibroblast-like shape into sphere-shaped cells with extending processes. Next-generation transcriptomics sequencing showed increased expression of neural progenitor markers such as NES, MEIS2, and MEST. In addition, de novo expression of neural precursor genes, such as NRN1, PHOX2B, VANGL2, and NTRK3, was noticed in passage 41. Immunocytochemistry results showed suppression of neurogenesis repressors TP53 and p21, whereas Western blot results revealed the expression of neurotrophic factors BDNF and NT3 at passage 41. Our results showed the spontaneous efficacy of hGMSCs to differentiate into neural precursor cells over prolonged passages and that these cells may assist in producing novel in vitro disease models that are associated with neural development.

Devices and circuits for nanoelectronic implementation of artificial neural networks

NASA Astrophysics Data System (ADS)

Turel, Ozgur

Biological neural networks perform complicated information processing tasks at speeds better than conventional computers based on conventional algorithms. This has inspired researchers to look into the way these networks function, and propose artificial networks that mimic their behavior. Unfortunately, most artificial neural networks, either software or hardware, do not provide either the speed or the complexity of a human brain. Nanoelectronics, with high density and low power dissipation that it provides, may be used in developing more efficient artificial neural networks. This work consists of two major contributions in this direction. First is the proposal of the CMOL concept, hybrid CMOS-molecular hardware [1-8]. CMOL may circumvent most of the problems in posed by molecular devices, such as low yield, vet provide high active device density, ˜1012/cm 2. The second contribution is CrossNets, artificial neural networks that are based on CMOL. We showed that CrossNets, with their fault tolerance, exceptional speed (˜ 4 to 6 orders of magnitude faster than biological neural networks) can perform any task any artificial neural network can perform. Moreover, there is a hope that if their integration scale is increased to that of human cerebral cortex (˜ 1010 neurons and ˜ 1014 synapses), they may be capable of performing more advanced tasks.

Artificial intelligence: Deep neural reasoning

NASA Astrophysics Data System (ADS)

Jaeger, Herbert

2016-10-01

The human brain can solve highly abstract reasoning problems using a neural network that is entirely physical. The underlying mechanisms are only partially understood, but an artificial network provides valuable insight. See Article p.471

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

PubMed

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

2015-01-01

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

Wireless, High-Bandwidth Recordings from Non-Human Primate Motor Cortex using a Scalable 16-Ch Implantable Microsystem

PubMed Central

Borton, David A.; Song, Yoon-Kyu; Patterson, William R.; Bull, Christopher W.; Park, Sunmee; Laiwalla, Farah; Donoghue, John P.; Nurmikko, Arto V.

2013-01-01

A multitude of neuroengineering challenges exist today in creating practical, chronic multichannel neural recording systems for primate research and human clinical application. Specifically, a) the persistent wired connections limit patient mobility from the recording system, b) the transfer of high bandwidth signals to external (even distant) electronics normally forces premature data reduction, and c) the chronic susceptibility to infection due to the percutaneous nature of the implants all severely hinder the success of neural prosthetic systems. Here we detail one approach to overcome these limitations: an entirely implantable, wirelessly communicating, integrated neural recording microsystem, dubbed the Brain Implantable Chip (BIC). PMID:19964128

Neural autonomic control in orthostatic intolerance.

PubMed

Furlan, Raffaello; Barbic, Franca; Casella, Francesco; Severgnini, Giorgio; Zenoni, Luca; Mercieri, Angelo; Mangili, Ruggero; Costantino, Giorgio; Porta, Alberto

2009-10-01

Inability to maintain the upright position is manifested by a number of symptoms shared by either human pathophysiology and conditions following weightlessness or bed rest. Alterations of the neural sympathetic cardiovascular control have been suggested to be one of the potential underlying etiopathogenetic mechanisms in these conditions. We hypothesize that the study of the autonomic profile of human orthostatic intolerance syndromes may furnish a valuable insight into the complexity of the sympathetic alterations leading to a reduced gravitational tolerance. In the present paper we describe abnormalities both in the magnitude and in the pattern of the sympathetic neural firing observed in patients affected by orthostatic intolerance, attending the upright position. Also, we discuss similarity and differences in the neural sympathetic mechanisms regulating the cardiovascular system during the gravitational stimulus both in clinical syndromes and in subjects returning from space.

Non-invasive neural stimulation

NASA Astrophysics Data System (ADS)

Tyler, William J.; Sanguinetti, Joseph L.; Fini, Maria; Hool, Nicholas

2017-05-01

Neurotechnologies for non-invasively interfacing with neural circuits have been evolving from those capable of sensing neural activity to those capable of restoring and enhancing human brain function. Generally referred to as non-invasive neural stimulation (NINS) methods, these neuromodulation approaches rely on electrical, magnetic, photonic, and acoustic or ultrasonic energy to influence nervous system activity, brain function, and behavior. Evidence that has been surmounting for decades shows that advanced neural engineering of NINS technologies will indeed transform the way humans treat diseases, interact with information, communicate, and learn. The physics underlying the ability of various NINS methods to modulate nervous system activity can be quite different from one another depending on the energy modality used as we briefly discuss. For members of commercial and defense industry sectors that have not traditionally engaged in neuroscience research and development, the science, engineering and technology required to advance NINS methods beyond the state-of-the-art presents tremendous opportunities. Within the past few years alone there have been large increases in global investments made by federal agencies, foundations, private investors and multinational corporations to develop advanced applications of NINS technologies. Driven by these efforts NINS methods and devices have recently been introduced to mass markets via the consumer electronics industry. Further, NINS continues to be explored in a growing number of defense applications focused on enhancing human dimensions. The present paper provides a brief introduction to the field of non-invasive neural stimulation by highlighting some of the more common methods in use or under current development today.

Neural tube defects in Waardenburg syndrome: A case report and review of the literature.

PubMed

Hart, Joseph; Miriyala, Kalpana

2017-09-01

Waardenburg syndrome type 1 (WS1) is an autosomal dominant genetic condition characterized by sensorineural deafness and pigment abnormalities, and is caused by variants in the PAX3 homeodomain. PAX3 variants have been associated with severe neural tube defects in mice and humans, but the frequency and clinical manifestations of this symptom remain largely unexplored in humans. Consequently, the role of PAX3 in human neural tube formation remains a study of interest, for clinical as well as research purposes. Though the association between spina bifida and WS1 is now well-documented, no study has attempted to characterize the range of spina bifida phenotypes seen in WS. Spina bifida encompasses several diagnoses with a wide scope of clinical severity, ranging from spina bifida occulta to myelomeningocele. We present a patient with Waardenburg syndrome type 1 caused by a novel missense variant in PAX3, presenting with myelomeningocele, Arnold-Chiari malformation, and hydrocephalus at birth. Additionally, we review 32 total cases of neural tube defects associated with WS. Including this report, there have been 15 published cases of myelomeningocele, 10 cases of unspecified spina bifida, 3 cases of sacral dimples, 0 cases of meningocele, and 4 cases of miscellaneous other neural tube defects. Though the true frequency of each phenotype cannot be determined from this collection of cases, these results demonstrate that Waardenburg syndrome type 1 carries a notable risk of severe neural tube defects, which has implications in prenatal and genetic counseling. © 2017 Wiley Periodicals, Inc.

Human-like brain hemispheric dominance in birdsong learning.

PubMed

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

2012-07-31

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

Neural decoding of collective wisdom with multi-brain computing.

PubMed

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

2012-01-02

Group decisions and even aggregation of multiple opinions lead to greater decision accuracy, a phenomenon known as collective wisdom. Little is known about the neural basis of collective wisdom and whether its benefits arise in late decision stages or in early sensory coding. Here, we use electroencephalography and multi-brain computing with twenty humans making perceptual decisions to show that combining neural activity across brains increases decision accuracy paralleling the improvements shown by aggregating the observers' opinions. Although the largest gains result from an optimal linear combination of neural decision variables across brains, a simpler neural majority decision rule, ubiquitous in human behavior, results in substantial benefits. In contrast, an extreme neural response rule, akin to a group following the most extreme opinion, results in the least improvement with group size. Analyses controlling for number of electrodes and time-points while increasing number of brains demonstrate unique benefits arising from integrating neural activity across different brains. The benefits of multi-brain integration are present in neural activity as early as 200 ms after stimulus presentation in lateral occipital sites and no additional benefits arise in decision related neural activity. Sensory-related neural activity can predict collective choices reached by aggregating individual opinions, voting results, and decision confidence as accurately as neural activity related to decision components. Estimation of the potential for the collective to execute fast decisions by combining information across numerous brains, a strategy prevalent in many animals, shows large time-savings. Together, the findings suggest that for perceptual decisions the neural activity supporting collective wisdom and decisions arises in early sensory stages and that many properties of collective cognition are explainable by the neural coding of information across multiple brains. Finally, our methods highlight the potential of multi-brain computing as a technique to rapidly and in parallel gather increased information about the environment as well as to access collective perceptual/cognitive choices and mental states. Copyright © 2011 Elsevier Inc. All rights reserved.

Network evolution induced by asynchronous stimuli through spike-timing-dependent plasticity.

PubMed

Yuan, Wu-Jie; Zhou, Jian-Fang; Zhou, Changsong

2013-01-01

In sensory neural system, external asynchronous stimuli play an important role in perceptual learning, associative memory and map development. However, the organization of structure and dynamics of neural networks induced by external asynchronous stimuli are not well understood. Spike-timing-dependent plasticity (STDP) is a typical synaptic plasticity that has been extensively found in the sensory systems and that has received much theoretical attention. This synaptic plasticity is highly sensitive to correlations between pre- and postsynaptic firings. Thus, STDP is expected to play an important role in response to external asynchronous stimuli, which can induce segregative pre- and postsynaptic firings. In this paper, we study the impact of external asynchronous stimuli on the organization of structure and dynamics of neural networks through STDP. We construct a two-dimensional spatial neural network model with local connectivity and sparseness, and use external currents to stimulate alternately on different spatial layers. The adopted external currents imposed alternately on spatial layers can be here regarded as external asynchronous stimuli. Through extensive numerical simulations, we focus on the effects of stimulus number and inter-stimulus timing on synaptic connecting weights and the property of propagation dynamics in the resulting network structure. Interestingly, the resulting feedforward structure induced by stimulus-dependent asynchronous firings and its propagation dynamics reflect both the underlying property of STDP. The results imply a possible important role of STDP in generating feedforward structure and collective propagation activity required for experience-dependent map plasticity in developing in vivo sensory pathways and cortices. The relevance of the results to cue-triggered recall of learned temporal sequences, an important cognitive function, is briefly discussed as well. Furthermore, this finding suggests a potential application for examining STDP by measuring neural population activity in a cultured neural network.

Neural and Synaptic Defects in slytherin a Zebrafish Model for Human Congenital Disorders of Glycosylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Y Song; J Willer; P Scherer

2011-12-31

Congenital disorder of glycosylation type IIc (CDG IIc) is characterized by mental retardation, slowed growth and severe immunodeficiency, attributed to the lack of fucosylated glycoproteins. While impaired Notch signaling has been implicated in some aspects of CDG IIc pathogenesis, the molecular and cellular mechanisms remain poorly understood. We have identified a zebrafish mutant slytherin (srn), which harbors a missense point mutation in GDP-mannose 4,6 dehydratase (GMDS), the rate-limiting enzyme in protein fucosylation, including that of Notch. Here we report that some of the mechanisms underlying the neural phenotypes in srn and in CGD IIc are Notch-dependent, while others are Notch-independent.more » We show, for the first time in a vertebrate in vivo, that defects in protein fucosylation leads to defects in neuronal differentiation, maintenance, axon branching, and synapse formation. Srn is thus a useful and important vertebrate model for human CDG IIc that has provided new insights into the neural phenotypes that are hallmarks of the human disorder and has also highlighted the role of protein fucosylation in neural development.« less

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

PubMed

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

2016-10-01

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. 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. 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. 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 across cortical areas during activity.

Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

PubMed Central

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

Spatial resolution dependence on spectral frequency in human speech cortex electrocorticography

NASA Astrophysics Data System (ADS)

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 across cortical areas during activity.

Human adenovirus serotypes 4p and 11p are efficiently expressed in cell lines of neural tumour origin.

PubMed

Skog, Johan; Mei, Ya-Fang; Wadell, Göran

2002-06-01

Most currently used adenovirus vectors are based upon adenovirus serotypes 2 and 5 (Ad2 and Ad5), which have limited efficiencies for gene transfer to human neural cells. Both serotypes bind to the known adenovirus receptor, CAR (coxsackievirus and adenovirus receptor), and have restricted cell tropism. The purpose of this study was to find vector candidates that are superior to Ad5 in infecting human neural tumours. Using flow cytometry, the vector candidates Ad4p, Ad11p and Ad17p were compared to the commonly used adenovirus vector Ad5v for their binding capacity to neural cell lines derived from glioblastoma, medulloblastoma and neuroblastoma cell lines. The production of viral structural proteins and the CAR-binding properties of the different serotypes were also assessed in these cells. Computer-based models of the fibre knobs of Ad4p and Ad17 were created based upon the crystallized fibre knob structure of adenoviruses and analysed for putative receptor-interacting regions that differed from the fibre knob of Ad5. The non CAR-binding vector candidate Ad11p showed clearly the best binding capacity to all of the neural cell lines, binding more than 90% of cells of all of the neural cell lines tested, in contrast to 20% or less for the commonly used vector Ad5v. Ad4p and Ad11p were also internalized and produced viral proteins more successfully than Ad5. Ad4p showed a low binding ability but a very efficient capacity for infection in cell culture. Ad17p virions neither bound or efficiently infected any of the neural cell lines studied.

UTP – Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells

PubMed Central

Liñán-Rico, Andromeda; Ochoa-Cortes, Fernando; Zuleta-Alarcon, Alix; Alhaj, Mazin; Tili, Esmerina; Enneking, Josh; Harzman, Alan; Grants, Iveta; Bergese, Sergio; Christofi, Fievos L.

2017-01-01

Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca2+-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells. Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca2+imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC). Results: UTP, UTPγS, UDP or ATP induced Ca2+oscillations in BON. UTP evoked a biphasic concentration-dependent Ca2+response. Cells responded in the order of UTP, ATP > UTPγS > UDP >> MRS2768, BzATP, α,β-MeATP > MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y4, 50% cells), UDP (P2Y6, 30%), UTPγS and UDP (14%) or MRS2768 (<3%). UTP Ca2+responses were blocked with inhibitors of PLC, IP3R, SERCA Ca2+pump, La3+sensitive Ca2+channels or chelation of intracellular free Ca2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca2+pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca2+currents (ICa), Vm-depolarization and inhibited IK (not IA) currents. An IKv7.2/7.3 K+ channel blocker XE-991 mimicked UTP-induced Vm-depolarization and blocked UTP-responses. XE-991 blocked IK and UTP caused further reduction. La3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca2+buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y4/P2Y6R. Zero-Ca2+buffer augmented Ca2+responses and 5-HT release. Conclusion: UTP activates a predominant P2Y4R pathway to trigger Ca2+oscillations via internal Ca2+mobilization through a PLC/IP3/IP3R/SERCA Ca2+signaling pathway to stimulate 5-HT release; Ca2+influx is inhibitory. UTP-induced Vm-depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca2+oscillations or Ica/VOCC). UTP-gated signaling pathways triggered by activation of P2Y4R stimulate 5-HT release. PMID:28751862

UTP - Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells.

PubMed

Liñán-Rico, Andromeda; Ochoa-Cortes, Fernando; Zuleta-Alarcon, Alix; Alhaj, Mazin; Tili, Esmerina; Enneking, Josh; Harzman, Alan; Grants, Iveta; Bergese, Sergio; Christofi, Fievos L

2017-01-01

Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca 2+ -dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells. Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca 2+ imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC). Results: UTP, UTPγS, UDP or ATP induced Ca 2+ oscillations in BON. UTP evoked a biphasic concentration-dependent Ca 2+ response. Cells responded in the order of UTP, ATP > UTPγS > UDP > MRS2768, BzATP, α,β-MeATP > MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y 4 , 50% cells), UDP (P2Y 6 , 30%), UTPγS and UDP (14%) or MRS2768 (<3%). UTP Ca 2+ responses were blocked with inhibitors of PLC, IP3R, SERCA Ca 2+ pump, La 3+ sensitive Ca 2+ channels or chelation of intracellular free Ca 2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca 2+ pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca 2+ currents (I Ca ), V m -depolarization and inhibited I K (not I A ) currents. An I Kv 7.2/7.3 K + channel blocker XE-991 mimicked UTP-induced V m -depolarization and blocked UTP-responses. XE-991 blocked I K and UTP caused further reduction. La 3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca 2+ buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y 4 /P2Y 6 R. Zero-Ca 2+ buffer augmented Ca 2+ responses and 5-HT release. Conclusion: UTP activates a predominant P2Y 4 R pathway to trigger Ca 2+ oscillations via internal Ca 2+ mobilization through a PLC/IP 3 /IP3R/SERCA Ca 2+ signaling pathway to stimulate 5-HT release; Ca 2+ influx is inhibitory. UTP-induced V m -depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca 2+ oscillations or I ca /VOCC). UTP-gated signaling pathways triggered by activation of P2Y 4 R stimulate 5-HT release.

The Relationship Between Visual Sensor Equipment in Flying Insects and their Flight Performance -- a Neurobio-Engineering Approach

DTIC Science & Technology

2014-03-16

College in the Department of Bioengineering with: Dr Martyn Boutelle (Biosensors), Dr Simon Schultz (Neural Coding), Dr Manos Drakakis (Low-power VLSI...in the fly gaze stabilization system. PLoS Biology, 6(7):e173 (2008). O27. Saleem A, Krapp H.G., and Schultz S.R.: Spike-triggered independent...D., Krapp H.G., Schultz S.R.: Bimodal optomotor response to plaids in blowflies: mechanisms of component selectivity and evidence for pattern

Drive Control Scheme of Electric Power Assisted Wheelchair Based on Neural Network Learning of Human Wheelchair Operation Characteristics

NASA Astrophysics Data System (ADS)

Tanohata, Naoki; Seki, Hirokazu

This paper describes a novel drive control scheme of electric power assisted wheelchairs based on neural network learning of human wheelchair operation characteristics. “Electric power assisted wheelchair” which enhances the drive force of the operator by employing electric motors is expected to be widely used as a mobility support system for elderly and disabled people. However, some handicapped people with paralysis of the muscles of one side of the body cannot maneuver the wheelchair as desired because of the difference in the right and left input force. Therefore, this study proposes a neural network learning system of such human wheelchair operation characteristics and a drive control scheme with variable distribution and assistance ratios. Some driving experiments will be performed to confirm the effectiveness of the proposed control system.

Development and application of deep convolutional neural network in target detection

NASA Astrophysics Data System (ADS)

Jiang, Xiaowei; Wang, Chunping; Fu, Qiang

2018-04-01

With the development of big data and algorithms, deep convolution neural networks with more hidden layers have more powerful feature learning and feature expression ability than traditional machine learning methods, making artificial intelligence surpass human level in many fields. This paper first reviews the development and application of deep convolutional neural networks in the field of object detection in recent years, then briefly summarizes and ponders some existing problems in the current research, and the future development of deep convolutional neural network is prospected.

Inhibition of Excessive Monoamine Oxidase A/B Activity Protects Against Stress-induced Neuronal Death in Huntington Disease.

PubMed

Ooi, Jolene; Hayden, Michael R; Pouladi, Mahmoud A

2015-12-01

Monoamine oxidases (MAO) are important components of the homeostatic machinery that maintains the levels of monoamine neurotransmitters, including dopamine, in balance. Given the imbalance in dopamine levels observed in Huntington disease (HD), the aim of this study was to examine MAO activity in a mouse striatal cell model of HD and in human neural cells differentiated from control and HD patient-derived induced pluripotent stem cell (hiPSC) lines. We show that mouse striatal neural cells expressing mutant huntingtin (HTT) exhibit increased MAO expression and activity. We demonstrate using luciferase promoter assays that the increased MAO expression reflects enhanced epigenetic activation in striatal neural cells expressing mutant HTT. Using cellular stress paradigms, we further demonstrate that the increase in MAO activity in mutant striatal neural cells is accompanied by enhanced susceptibility to oxidative stress and impaired viability. Treatment of mutant striatal neural cells with MAO inhibitors ameliorated oxidative stress and improved cellular viability. Finally, we demonstrate that human HD neural cells exhibit increased MAO-A and MAO-B expression and activity. Altogether, this study demonstrates abnormal MAO expression and activity and suggests a potential use for MAO inhibitors in HD.

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

PubMed

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.

The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene.

PubMed

Cai, Pei-qiang; Tang, Xun; Lin, Yue-qiu; Martin, Oudega; Sun, Guang-yun; Xu, Lin; Yang, Yun-kang; Zhou, Tian-hua

2006-02-01

To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs) mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI). Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3 (NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot. Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot. Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

A 3D human neural cell culture system for modeling Alzheimer’s disease

PubMed Central

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

The Future of Contextual Fear Learning for PTSD Research: A Methodological Review of Neuroimaging Studies.

PubMed

Glenn, Daniel E; Risbrough, Victoria B; Simmons, Alan N; Acheson, Dean T; Stout, Daniel M

2017-10-21

There has been a great deal of recent interest in human models of contextual fear learning, particularly due to the use of such paradigms for investigating neural mechanisms related to the etiology of posttraumatic stress disorder. However, the construct of "context" in fear conditioning research is broad, and the operational definitions and methods used to investigate contextual fear learning in humans are wide ranging and lack specificity, making it difficult to interpret findings about neural activity. Here we will review neuroimaging studies of contextual fear acquisition in humans. We will discuss the methodology associated with four broad categories of how contextual fear learning is manipulated in imaging studies (colored backgrounds, static picture backgrounds, virtual reality, and configural stimuli) and highlight findings for the primary neural circuitry involved in each paradigm. Additionally, we will offer methodological recommendations for human studies of contextual fear acquisition, including using stimuli that distinguish configural learning from discrete cue associations and clarifying how context is experimentally operationalized.

Nuclear translocation of PKCα isoenzyme is involved in neurogenic commitment of human neural crest-derived periodontal ligament stem cells.

PubMed

Trubiani, Oriana; Guarnieri, Simone; Diomede, Francesca; Mariggiò, Maria A; Merciaro, Ilaria; Morabito, Caterina; Cavalcanti, Marcos F X B; Cocco, Lucio; Ramazzotti, Giulia

2016-11-01

Stem cells isolated from human adult tissue niche represent a promising source for neural differentiation. Human Periodontal Ligament Stem Cells (hPDLSCs) originating from the neural crest are particularly suitable for induction of neural commitment. In this study, under xeno-free culture conditions, in undifferentiated hPDLSCs and in hPDLSCs induced to neuronal differentiation by basic Fibroblast Growth Factor, the level of some neural markers have been analyzed. The hPDLSCs spontaneously express Nestin, a neural progenitor marker. In these cells, the neurogenic process induced to rearrange the cytoskeleton, form neurospheres and express higher levels of Nestin and Tyrosine Hydroxylase, indicating neural induction. Protein Kinase C (PKC) is highly expressed in neural tissue and has a key role in neuronal functions. In particular the Ca(2+) and diacylglycerol-dependent activation of PKCα isozyme is involved in the regulation of neuronal differentiation. Another main component of the pathways controlling neuronal differentiation is the Growth Associated Protein-43 (GAP-43), whose activity is strictly regulated by PKC. The aim of this study is to investigate the role of PKCα/GAP-43 nuclear signal transduction pathway during neuronal commitment of hPDLSCs. During hPDLSCs neurogenic commitment the levels of p-PKC and p-GAP-43 increased both in cytoplasmic and nuclear compartment. PKCα nuclear translocation induced GAP-43 movement to the cytoplasm, where it is known to regulate growth cone dynamics and neuronal differentiation. Moreover, the degree of cytosolic Ca(2+) mobilization appeared to be more pronounced in differentiated hPDLSCs than in undifferentiated cells. This study provides evidences of a new PKCα/GAP-43 nuclear signalling pathway that controls neuronal differentiation in hPDLSCs, leading the way to a potential use of these cells in cell-based therapy in neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitochondrial metabolism in early neural fate and its relevance for neuronal disease modeling.

PubMed

Lorenz, Carmen; Prigione, Alessandro

2017-12-01

Modulation of energy metabolism is emerging as a key aspect associated with cell fate transition. The establishment of a correct metabolic program is particularly relevant for neural cells given their high bioenergetic requirements. Accordingly, diseases of the nervous system commonly involve mitochondrial impairment. Recent studies in animals and in neural derivatives of human pluripotent stem cells (PSCs) highlighted the importance of mitochondrial metabolism for neural fate decisions in health and disease. The mitochondria-based metabolic program of early neurogenesis suggests that PSC-derived neural stem cells (NSCs) may be used for modeling neurological disorders. Understanding how metabolic programming is orchestrated during neural commitment may provide important information for the development of therapies against conditions affecting neural functions, including aging and mitochondrial disorders. Copyright © 2017. Published by Elsevier Ltd.

Genome Editing in Neuroepithelial Stem Cells to Generate Human Neurons with High Adenosine-Releasing Capacity.

PubMed

Poppe, Daniel; Doerr, Jonas; Schneider, Marion; Wilkens, Ruven; Steinbeck, Julius A; Ladewig, Julia; Tam, Allison; Paschon, David E; Gregory, Philip D; Reik, Andreas; Müller, Christa E; Koch, Philipp; Brüstle, Oliver

2018-06-01

As a powerful regulator of cellular homeostasis and metabolism, adenosine is involved in diverse neurological processes including pain, cognition, and memory. Altered adenosine homeostasis has also been associated with several diseases such as depression, schizophrenia, or epilepsy. Based on its protective properties, adenosine has been considered as a potential therapeutic agent for various brain disorders. Since systemic application of adenosine is hampered by serious side effects such as vasodilatation and cardiac suppression, recent studies aim at improving local delivery by depots, pumps, or cell-based applications. Here, we report on the characterization of adenosine-releasing human embryonic stem cell-derived neuroepithelial stem cells (long-term self-renewing neuroepithelial stem [lt-NES] cells) generated by zinc finger nuclease (ZFN)-mediated knockout of the adenosine kinase (ADK) gene. ADK-deficient lt-NES cells and their differentiated neuronal and astroglial progeny exhibit substantially elevated release of adenosine compared to control cells. Importantly, extensive adenosine release could be triggered by excitation of differentiated neuronal cultures, suggesting a potential activity-dependent regulation of adenosine supply. Thus, ZFN-modified neural stem cells might serve as a useful vehicle for the activity-dependent local therapeutic delivery of adenosine into the central nervous system. Stem Cells Translational Medicine 2018;7:477-486. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Event-Triggered Distributed Approximate Optimal State and Output Control of Affine Nonlinear Interconnected Systems.

PubMed

Narayanan, Vignesh; Jagannathan, Sarangapani

2017-06-08

This paper presents an approximate optimal distributed control scheme for a known interconnected system composed of input affine nonlinear subsystems using event-triggered state and output feedback via a novel hybrid learning scheme. First, the cost function for the overall system is redefined as the sum of cost functions of individual subsystems. A distributed optimal control policy for the interconnected system is developed using the optimal value function of each subsystem. To generate the optimal control policy, forward-in-time, neural networks are employed to reconstruct the unknown optimal value function at each subsystem online. In order to retain the advantages of event-triggered feedback for an adaptive optimal controller, a novel hybrid learning scheme is proposed to reduce the convergence time for the learning algorithm. The development is based on the observation that, in the event-triggered feedback, the sampling instants are dynamic and results in variable interevent time. To relax the requirement of entire state measurements, an extended nonlinear observer is designed at each subsystem to recover the system internal states from the measurable feedback. Using a Lyapunov-based analysis, it is demonstrated that the system states and the observer errors remain locally uniformly ultimately bounded and the control policy converges to a neighborhood of the optimal policy. Simulation results are presented to demonstrate the performance of the developed controller.

What can stimulus polarity and interphase gap tell us about auditory nerve function in cochlear-implant recipients?

PubMed

Hughes, Michelle L; Choi, Sangsook; Glickman, Erin

2018-03-01

Modeling studies suggest that differences in neural responses between polarities might reflect underlying neural health. Specifically, large differences in electrically evoked compound action potential (eCAP) amplitudes and amplitude-growth-function (AGF) slopes between polarities might reflect poorer peripheral neural health, whereas more similar eCAP responses between polarities might reflect better neural health. The interphase gap (IPG) has also been shown to relate to neural survival in animal studies. Specifically, healthy neurons exhibit larger eCAP amplitudes, lower thresholds, and steeper AGF slopes for increasing IPGs. In ears with poorer neural survival, these changes in neural responses are generally less apparent with increasing IPG. The primary goal of this study was to examine the combined effects of stimulus polarity and IPG within and across subjects to determine whether both measures represent similar underlying mechanisms related to neural health. With the exception of one measure in one group of subjects, results showed that polarity and IPG effects were generally not correlated in a systematic or predictable way. This suggests that these two effects might represent somewhat different aspects of neural health, such as differences in site of excitation versus integrative membrane characteristics, for example. Overall, the results from this study suggest that the underlying mechanisms that contribute to polarity and IPG effects in human CI recipients might be difficult to determine from animal models that do not exhibit the same anatomy, variance in etiology, electrode placement, and duration of deafness as humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective.

PubMed

Krystal, John H; Anticevic, Alan; Yang, Genevieve J; Dragoi, George; Driesen, Naomi R; Wang, Xiao-Jing; Murray, John D

2017-05-15

The functional optimization of neural ensembles is central to human higher cognitive functions. When the functions through which neural activity is tuned fail to develop or break down, symptoms and cognitive impairments arise. This review considers ways in which disturbances in the balance of excitation and inhibition might develop and be expressed in cortical networks in association with schizophrenia. This presentation is framed within a developmental perspective that begins with disturbances in glutamate synaptic development in utero. It considers developmental correlates and consequences, including compensatory mechanisms that increase intrinsic excitability or reduce inhibitory tone. It also considers the possibility that these homeostatic increases in excitability have potential negative functional and structural consequences. These negative functional consequences of disinhibition may include reduced working memory-related cortical activity associated with the downslope of the "inverted-U" input-output curve, impaired spatial tuning of neural activity and impaired sparse coding of information, and deficits in the temporal tuning of neural activity and its implication for neural codes. The review concludes by considering the functional significance of noisy activity for neural network function. The presentation draws on computational neuroscience and pharmacologic and genetic studies in animals and humans, particularly those involving N-methyl-D-aspartate glutamate receptor antagonists, to illustrate principles of network regulation that give rise to features of neural dysfunction associated with schizophrenia. While this presentation focuses on schizophrenia, the general principles outlined in the review may have broad implications for considering disturbances in the regulation of neural ensembles in psychiatric disorders. Published by Elsevier Inc.

A Brain for Speech. Evolutionary Continuity in Primate and Human Auditory-Vocal Processing

PubMed Central

Aboitiz, Francisco

2018-01-01

In this review article, I propose a continuous evolution from the auditory-vocal apparatus and its mechanisms of neural control in non-human primates, to the peripheral organs and the neural control of human speech. Although there is an overall conservatism both in peripheral systems and in central neural circuits, a few changes were critical for the expansion of vocal plasticity and the elaboration of proto-speech in early humans. Two of the most relevant changes were the acquisition of direct cortical control of the vocal fold musculature and the consolidation of an auditory-vocal articulatory circuit, encompassing auditory areas in the temporoparietal junction and prefrontal and motor areas in the frontal cortex. This articulatory loop, also referred to as the phonological loop, enhanced vocal working memory capacity, enabling early humans to learn increasingly complex utterances. The auditory-vocal circuit became progressively coupled to multimodal systems conveying information about objects and events, which gradually led to the acquisition of modern speech. Gestural communication accompanies the development of vocal communication since very early in human evolution, and although both systems co-evolved tightly in the beginning, at some point speech became the main channel of communication. PMID:29636657

Scientific, Engineering, and Financial Factors of the 1989 Human-Triggered Newcastle Earthquake in Australia

NASA Astrophysics Data System (ADS)

Klose, C. D.

2006-12-01

This presentation emphasizes the dualism of natural resources exploitation and economic growth versus geomechanical pollution and risks of human-triggered earthquakes. Large-scale geoengineering activities, e.g., mining, reservoir impoundment, oil/gas production, water exploitation or fluid injection, alter pre-existing lithostatic stress states in the earth's crust and are anticipated to trigger earthquakes. Such processes of in- situ stress alteration are termed geomechanical pollution. Moreover, since the 19th century more than 200 earthquakes have been documented worldwide with a seismic moment magnitude of 4.5

A neural network for intermale aggression to establish social hierarchy.

PubMed

Stagkourakis, Stefanos; Spigolon, Giada; Williams, Paul; Protzmann, Jil; Fisone, Gilberto; Broberger, Christian

2018-06-01

Intermale aggression is used to establish social rank. Several neuronal populations have been implicated in aggression, but the circuit mechanisms that shape this innate behavior and coordinate its different components (including attack execution and reward) remain elusive. We show that dopamine transporter-expressing neurons in the hypothalamic ventral premammillary nucleus (PMv DAT neurons) organize goal-oriented aggression in male mice. Activation of PMv DAT neurons triggers attack behavior; silencing these neurons interrupts attacks. Regenerative PMv DAT membrane conductances interacting with recurrent and reciprocal excitation explain how a brief trigger can elicit a long-lasting response (hysteresis). PMv DAT projections to the ventrolateral part of the ventromedial hypothalamic and the supramammillary nuclei control attack execution and aggression reward, respectively. Brief manipulation of PMv DAT activity switched the dominance relationship between males, an effect persisting for weeks. These results identify a network structure anchored in PMv DAT neurons that organizes aggressive behavior and, as a consequence, determines intermale hierarchy.

In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barbon, Silvia, E-mail: silvia.barbon@yahoo.it

In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in themore » future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was accomplished after cell treatment. • TAT-CNTF can be efficiently loaded on oxidized PVA cylinders for local delivery. • TAT-CNTF features make it ideal for peripheral nerve regeneration therapies.« less

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

PubMed

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.

Nonequilibrium landscape theory of neural networks.

PubMed

Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

2013-11-05

The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape-flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments.

Nonequilibrium landscape theory of neural networks

PubMed Central

Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

2013-01-01

The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape–flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments. PMID:24145451

Effect of an 8-week practice of externally triggered speech on basal ganglia activity of stuttering and fluent speakers.

PubMed

Toyomura, Akira; Fujii, Tetsunoshin; Kuriki, Shinya

2015-04-01

The neural mechanisms underlying stuttering are not well understood. It is known that stuttering appears when persons who stutter speak in a self-paced manner, but speech fluency is temporarily increased when they speak in unison with external trigger such as a metronome. This phenomenon is very similar to the behavioral improvement by external pacing in patients with Parkinson's disease. Recent imaging studies have also suggested that the basal ganglia are involved in the etiology of stuttering. In addition, previous studies have shown that the basal ganglia are involved in self-paced movement. Then, the present study focused on the basal ganglia and explored whether long-term speech-practice using external triggers can induce modification of the basal ganglia activity of stuttering speakers. Our study of functional magnetic resonance imaging revealed that stuttering speakers possessed significantly lower activity in the basal ganglia than fluent speakers before practice, especially when their speech was self-paced. After an 8-week speech practice of externally triggered speech using a metronome, the significant difference in activity between the two groups disappeared. The cerebellar vermis of stuttering speakers showed significantly decreased activity during the self-paced speech in the second compared to the first experiment. The speech fluency and naturalness of the stuttering speakers were also improved. These results suggest that stuttering is associated with defective motor control during self-paced speech, and that the basal ganglia and the cerebellum are involved in an improvement of speech fluency of stuttering by the use of external trigger. Copyright © 2015 Elsevier Inc. All rights reserved.

Midfrontal Theta and Posterior Parietal Alpha Band Oscillations Support Conflict Resolution in a Masked Affective Priming Task.

PubMed

Jiang, Jun; Bailey, Kira; Xiao, Xiao

2018-01-01

Past attempts to characterize the neural mechanisms of affective priming have conceptualized it in terms of classic cognitive conflict, but have not examined the neural oscillatory mechanisms of subliminal affective priming. Using behavioral and electroencephalogram (EEG) time frequency (TF) analysis, the current study examines the oscillatory dynamics of unconsciously triggered conflict in an emotional facial expressions version of the masked affective priming task. The results demonstrate that the power dynamics of conflict are characterized by increased midfrontal theta activity and suppressed parieto-occipital alpha activity. Across-subject and within-trial correlation analyses further confirmed this pattern. Phase synchrony and Granger causality analyses (GCAs) revealed that the fronto-parietal network was involved in unconscious conflict detection and resolution. Our findings support a response conflict account of affective priming, and reveal the role of the fronto-parietal network in unconscious conflict control.

Competition between items in working memory leads to forgetting.

PubMed

Lewis-Peacock, Jarrod A; Norman, Kenneth A

2014-12-18

Switching attention from one thought to the next propels our mental lives forward. However, it is unclear how this thought-juggling affects our ability to remember these thoughts. Here we show that competition between the neural representations of pictures in working memory can impair subsequent recognition of those pictures. We use pattern classifiers to decode functional magnetic resonance imaging (fMRI) data from a retro-cueing task where participants juggle two pictures in working memory. Trial-by-trial fluctuations in neural dynamics are predictive of performance on a surprise recognition memory test: trials that elicit similar levels of classifier evidence for both pictures (indicating close competition) are associated with worse memory performance than trials where participants switch decisively from thinking about one picture to the other. This result is consistent with the non-monotonic plasticity hypothesis, which predicts that close competition can trigger weakening of memories that lose the competition, leading to subsequent forgetting.

Imaging Neural Activity Using Thy1-GCaMP Transgenic mice

PubMed Central

Chen, Qian; Cichon, Joseph; Wang, Wenting; Qiu, Li; Lee, Seok-Jin R.; Campbell, Nolan R.; DeStefino, Nicholas; Goard, Michael J.; Fu, Zhanyan; Yasuda, Ryohei; Looger, Loren L.; Arenkiel, Benjamin R.; Gan, Wen-Biao; Feng, Guoping

2014-01-01

Summary The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain, and will greatly facilitate dissecting complex structural and functional relationships of neural networks. PMID:23083733

Handwritten dynamics assessment through convolutional neural networks: An application to Parkinson's disease identification.

PubMed

Pereira, Clayton R; Pereira, Danilo R; Rosa, Gustavo H; Albuquerque, Victor H C; Weber, Silke A T; Hook, Christian; Papa, João P

2018-05-01

Parkinson's disease (PD) is considered a degenerative disorder that affects the motor system, which may cause tremors, micrography, and the freezing of gait. Although PD is related to the lack of dopamine, the triggering process of its development is not fully understood yet. In this work, we introduce convolutional neural networks to learn features from images produced by handwritten dynamics, which capture different information during the individual's assessment. Additionally, we make available a dataset composed of images and signal-based data to foster the research related to computer-aided PD diagnosis. The proposed approach was compared against raw data and texture-based descriptors, showing suitable results, mainly in the context of early stage detection, with results nearly to 95%. The analysis of handwritten dynamics using deep learning techniques showed to be useful for automatic Parkinson's disease identification, as well as it can outperform handcrafted features. Copyright © 2018 Elsevier B.V. All rights reserved.

The vomeronasal system mediates sick conspecific avoidance.

PubMed

Boillat, Madlaina; Challet, Ludivine; Rossier, Daniel; Kan, Chenda; Carleton, Alan; Rodriguez, Ivan

2015-01-19

Although sociability offers many advantages, a major drawback is the increased risk of exposure to contagious pathogens, like parasites, viruses, or bacteria. Social species have evolved various behavioral strategies reducing the probability of pathogen exposure. In rodents, sick conspecific avoidance can be induced by olfactory cues emitted by parasitized or infected conspecifics. The neural circuits involved in this behavior remain largely unknown. We observed that olfactory cues present in bodily products of mice in an acute inflammatory state or infected with a viral pathogen are aversive to conspecifics. We found that these chemical signals trigger neural activity in the vomeronasal system, an olfactory subsystem controlling various innate behaviors. Supporting the functional relevance of these observations, we show that preference toward healthy individuals is abolished in mice with impaired vomeronasal function. These findings reveal a novel function played by the vomeronasal system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spike-timing dependent plasticity in primate corticospinal connections induced during free behavior

PubMed Central

Nishimura, Yukio; Perlmutter, Steve I.; Eaton, Ryan W.; Fetz, Eberhard E.

2014-01-01

Motor learning and functional recovery from brain damage involve changes in the strength of synaptic connections between neurons. Relevant in vivo evidence on the underlying cellular mechanisms remains limited and indirect. We found that the strength of neural connections between motor cortex and spinal cord in monkeys can be modified with an autonomous recurrent neural interface that delivers electrical stimuli in the spinal cord triggered by action potentials of corticospinal cells during free behavior. The activity-dependent stimulation modified the strength of the terminal connections of single corticomotoneuronal cells, consistent with a bidirectional spike-timing dependent plasticity rule previously derived from in vitro experiments. For some cells the changes lasted for days after the end of conditioning, but most effects eventually reverted to preconditioning levels. These results provide the first direct evidence of corticospinal synaptic plasticity in vivo at the level of single neurons induced by normal firing patterns during free behavior. PMID:24210907

A common neural circuit mechanism for internally guided and externally reinforced forms of motor learning.

PubMed

Hisey, Erin; Kearney, Matthew Gene; Mooney, Richard

2018-04-01

The complex skills underlying verbal and musical expression can be learned without external punishment or reward, indicating their learning is internally guided. The neural mechanisms that mediate internally guided learning are poorly understood, but a circuit comprising dopamine-releasing neurons in the midbrain ventral tegmental area (VTA) and their targets in the basal ganglia are important to externally reinforced learning. Juvenile zebra finches copy a tutor song in a process that is internally guided and, in adulthood, can learn to modify the fundamental frequency (pitch) of a target syllable in response to external reinforcement with white noise. Here we combined intersectional genetic ablation of VTA neurons, reversible blockade of dopamine receptors in the basal ganglia, and singing-triggered optogenetic stimulation of VTA terminals to establish that a common VTA-basal ganglia circuit enables internally guided song copying and externally reinforced syllable pitch learning.

Competition between items in working memory leads to forgetting

PubMed Central

Lewis-Peacock, Jarrod A.; Norman, Kenneth A.

2014-01-01

Switching attention from one thought to the next propels our mental lives forward. However, it is unclear how this thought-juggling affects our ability to remember these thoughts. Here we show that competition between the neural representations of pictures in working memory can impair subsequent recognition of those pictures. We use pattern classifiers to decode functional magnetic resonance imaging (fMRI) data from a retro-cueing task where participants juggle two pictures in working memory. Trial-by-trial fluctuations in neural dynamics are predictive of performance on a surprise recognition memory test: trials that elicit similar levels of classifier evidence for both pictures (indicating close competition) are associated with worse memory performance than trials where participants switch decisively from thinking about one picture to the other. This result is consistent with the non-monotonic plasticity hypothesis, which predicts that close competition can trigger weakening of memories that lose the competition, leading to subsequent forgetting. PMID:25519874

microRNA expression in the neural retina: Focus on Müller glia.

PubMed

Quintero, Heberto; Lamas, Mónica

2018-03-01

The neural retina hosts a unique specialized type of macroglial cell that not only preserves retinal homeostasis, function, and integrity but also may serve as a source of new neurons during regenerative processes: the Müller cell. Precise microRNA-driven mechanisms of gene regulation impel and direct the processes of Müller glia lineage acquisition from retinal progenitors during development, the triggering of their response to retinal degeneration and, in some cases, Müller cell reprogramming and regenerative events. In this review we survey the recent reports describing, through functional assays, the regulatory role of microRNAs in Müller cell physiology, differentiation potential, and retinal pathology. We discuss also the evidence based on expression analysis that points out the relevance of a Müller glia-specific microRNA signature that would orchestrate these processes. © 2017 Wiley Periodicals, Inc.

Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG).

PubMed

Singh, Neha Atulkumar; Mandal, Abul Kalam Azad; Khan, Zaved Ahmed

2016-06-07

Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) enforce an overwhelming social and economic burden on society. They are primarily characterized through the accumulation of modified proteins, which further trigger biological responses such as inflammation, oxidative stress, excitotoxicity and modulation of signalling pathways. In a hope for cure, these diseases have been studied extensively over the last decade to successfully develop symptom-oriented therapies. However, so far no definite cure has been found. Therefore, there is a need to identify a class of drug capable of reversing neural damage and preventing further neural death. This review therefore assesses the reliability of the neuroprotective benefits of epigallocatechin-gallate (EGCG) by shedding light on their biological, pharmacological, antioxidant and metal chelation properties, with emphasis on their ability to invoke a range of cellular mechanisms in the brain. It also discusses the possible use of nanotechnology to enhance the neuroprotective benefits of EGCG.

Neural mechanisms underlying sound-induced visual motion perception: An fMRI study.

PubMed

Hidaka, Souta; Higuchi, Satomi; Teramoto, Wataru; Sugita, Yoichi

2017-07-01

Studies of crossmodal interactions in motion perception have reported activation in several brain areas, including those related to motion processing and/or sensory association, in response to multimodal (e.g., visual and auditory) stimuli that were both in motion. Recent studies have demonstrated that sounds can trigger illusory visual apparent motion to static visual stimuli (sound-induced visual motion: SIVM): A visual stimulus blinking at a fixed location is perceived to be moving laterally when an alternating left-right sound is also present. Here, we investigated brain activity related to the perception of SIVM using a 7T functional magnetic resonance imaging technique. Specifically, we focused on the patterns of neural activities in SIVM and visually induced visual apparent motion (VIVM). We observed shared activations in the middle occipital area (V5/hMT), which is thought to be involved in visual motion processing, for SIVM and VIVM. Moreover, as compared to VIVM, SIVM resulted in greater activation in the superior temporal area and dominant functional connectivity between the V5/hMT area and the areas related to auditory and crossmodal motion processing. These findings indicate that similar but partially different neural mechanisms could be involved in auditory-induced and visually-induced motion perception, and neural signals in auditory, visual, and, crossmodal motion processing areas closely and directly interact in the perception of SIVM. Copyright © 2017 Elsevier B.V. All rights reserved.

Phenotypic chemical screening using a zebrafish neural crest EMT reporter identifies retinoic acid as an inhibitor of epithelial morphogenesis

PubMed Central

Jimenez, Laura; Wang, Jindong; Morrison, Monique A.; Whatcott, Clifford; Soh, Katherine K.; Warner, Steven; Bearss, David; Jette, Cicely A.; Stewart, Rodney A.

2016-01-01

ABSTRACT The epithelial-to-mesenchymal transition (EMT) is a highly conserved morphogenetic program essential for embryogenesis, regeneration and cancer metastasis. In cancer cells, EMT also triggers cellular reprogramming and chemoresistance, which underlie disease relapse and decreased survival. Hence, identifying compounds that block EMT is essential to prevent or eradicate disseminated tumor cells. Here, we establish a whole-animal-based EMT reporter in zebrafish for rapid drug screening, called Tg(snai1b:GFP), which labels epithelial cells undergoing EMT to produce sox10-positive neural crest (NC) cells. Time-lapse and lineage analysis of Tg(snai1b:GFP) embryos reveal that cranial NC cells delaminate from two regions: an early population delaminates adjacent to the neural plate, whereas a later population delaminates from within the dorsal neural tube. Treating Tg(snai1b:GFP) embryos with candidate small-molecule EMT-inhibiting compounds identified TP-0903, a multi-kinase inhibitor that blocked cranial NC cell delamination in both the lateral and medial populations. RNA sequencing (RNA-Seq) analysis and chemical rescue experiments show that TP-0903 acts through stimulating retinoic acid (RA) biosynthesis and RA-dependent transcription. These studies identify TP-0903 as a new therapeutic for activating RA in vivo and raise the possibility that RA-dependent inhibition of EMT contributes to its prior success in eliminating disseminated cancer cells. PMID:26794130

Neural Integration of Information Specifying Human Structure from Form, Motion, and Depth

PubMed Central

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

Neural correlates for perception of companion animal photographs.

PubMed

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.