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  1. Neural circuitry for rat recognition memory.

    Science.gov (United States)

    Warburton, E C; Brown, M W

    2015-05-15

    Information concerning the roles of different brain regions in recognition memory processes is reviewed. The review concentrates on findings from spontaneous recognition memory tasks performed by rats, including memory for single objects, locations, object-location associations and temporal order. Particular emphasis is given to the potential roles of different regions in the circuit of interacting structures involving the perirhinal cortex, hippocampus, medial prefrontal cortex and medial dorsal thalamus in recognition memory for the association of objects and places. It is concluded that while all structures in this circuit play roles critical to such memory, these roles can potentially be differentiated and differences in the underlying synaptic and biochemical processes involved in each region are beginning to be uncovered. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Blueprints for behavior: genetic specification of neural circuitry for innate behaviors.

    Science.gov (United States)

    Manoli, Devanand S; Meissner, Geoffrey W; Baker, Bruce S

    2006-08-01

    Innate behaviors offer a unique opportunity to use genetic analysis to dissect and characterize the neural substrates of complex behavioral programs. Courtship in Drosophila involves a complex series of stereotyped behaviors that include numerous exchanges of multimodal sensory information over time. As we will discuss in this review, recent work has demonstrated that male-specific expression of Fruitless transcription factors (Fru(M) proteins) is necessary and sufficient to confer the potential for male courtship behaviors. Fru(M) factors program neurons of the male central and peripheral nervous systems whose function is dedicated to sexual behaviors. This circuitry seems to integrate sensory information to define behavioral states and regulate conserved neural elements for sex-specific behavioral output. The principles that govern the circuitry specified by Fru(M) expression might also operate in subcortical networks that govern innate behaviors in mammals.

  3. Neural circuitry underlying affective response to peer feedback in adolescence.

    Science.gov (United States)

    Guyer, Amanda E; Choate, Victoria R; Pine, Daniel S; Nelson, Eric E

    2012-01-01

    Peer feedback affects adolescents' behaviors, cognitions and emotions. We examined neural circuitry underlying adolescents' emotional response to peer feedback using a functional neuroimaging paradigm whereby, 36 adolescents (aged 9-17 years) believed they would interact with unknown peers postscan. Neural activity was expected to vary based on adolescents' perceptions of peers and feedback type. Ventrolateral prefrontal cortex (vlPFC) activity was found when adolescents indicated how they felt following feedback (acceptance or rejection) from peers of low vs high interest. Greater activation in both cortical (e.g. superior temporal gyrus, insula, anterior cingulate) and subcortical (e.g. striatum, thalamus) regions emerged in response to acceptance vs rejection feedback. Response to acceptance also varied by age and gender in similar regions (e.g. superior temporal gyrus, fusiform, insula), with greater age-related increases in activation to acceptance vs rejection for females than males. Affective response to rejection vs acceptance did not yield significantly greater neural activity in any region. vlPFC response suggests cognitive flexibility in reappraising initial perceptions of peers following feedback. Striatal response suggests that acceptance is a potent social reward for adolescents, an interpretation supported by more positive self-reported affective response to acceptance than rejection from high- but not low-interest peers.

  4. Imaging the neural circuitry and chemical control of aggressive motivation

    Directory of Open Access Journals (Sweden)

    Blanchard D Caroline

    2008-11-01

    Full Text Available Abstract Background With the advent of functional magnetic resonance imaging (fMRI in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior. Results To trigger aggressive motivation, male rats were presented with their female cage mate plus a novel male intruder in the bore of the magnet during image acquisition. As expected, brain areas previously identified as critical in the organization and expression of aggressive behavior were activated, e.g., lateral hypothalamus, medial basal amygdala. Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei. Oral administration of a selective vasopressin V1a receptor antagonist SRX251 or the selective serotonin reuptake inhibitor fluoxetine, drugs that block aggressive behavior, both caused a general suppression of the distributed neural circuit involved in aggressive motivation. However, the effect of SRX251, but not fluoxetine, was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected. Conclusion The putative neural circuit of aggressive motivation identified with fMRI includes neural substrates contributing to emotional expression (i.e. cortical and medial amygdala, BNST, lateral hypothalamus, emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex and the anterior thalamic nuclei that bridge the motor and cognitive components of aggressive responding

  5. Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

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    Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

    2016-04-01

    Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

  6. Mechanisms of Long Non-Coding RNAs in the Assembly and Plasticity of Neural Circuitry.

    Science.gov (United States)

    Wang, Andi; Wang, Junbao; Liu, Ying; Zhou, Yan

    2017-01-01

    The mechanisms underlying development processes and functional dynamics of neural circuits are far from understood. Long non-coding RNAs (lncRNAs) have emerged as essential players in defining identities of neural cells, and in modulating neural activities. In this review, we summarized latest advances concerning roles and mechanisms of lncRNAs in assembly, maintenance and plasticity of neural circuitry, as well as lncRNAs' implications in neurological disorders. We also discussed technical advances and challenges in studying functions and mechanisms of lncRNAs in neural circuitry. Finally, we proposed that lncRNA studies would advance our understanding on how neural circuits develop and function in physiology and disease conditions.

  7. Neural circuitry underlying sentence-level linguistic prosody.

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    Tong, Yunxia; Gandour, Jackson; Talavage, Thomas; Wong, Donald; Dzemidzic, Mario; Xu, Yisheng; Li, Xiaojian; Lowe, Mark

    2005-11-01

    This study investigates the neural substrates underlying the perception of two sentence-level prosodic phenomena in Mandarin Chinese: contrastive stress (initial vs. final emphasis position) and intonation (declarative vs. interrogative modality). In an fMRI experiment, Chinese and English listeners were asked to selectively attend to either stress or intonation in paired 3-word sentences, and make speeded-response discrimination judgments. Between-group comparisons revealed that the Chinese group exhibited significantly greater activity in the left supramarginal gyrus and posterior middle temporal gyrus relative to the English group for both tasks. These same two regions showed a leftward asymmetry in the stress task for the Chinese group only. For both language groups, rightward asymmetries were observed in the middle portion of the middle frontal gyrus across tasks. All task effects involved greater activity for the stress task as compared to intonation. A left-sided task effect was observed in the posterior middle temporal gyrus for the Chinese group only. Both language groups exhibited a task effect bilaterally in the intraparietal sulcus. These findings support the emerging view that speech prosody perception involves a dynamic interplay among widely distributed regions not only within a single hemisphere but also between the two hemispheres. This model of speech prosody processing emphasizes the role of right hemisphere regions for complex-sound analysis, whereas task-dependent regions in the left hemisphere predominate when language processing is required.

  8. Retina neural circuitry seen with particle detector technology

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    Using particle physics techniques, high energy physics researchers have recently provided new insight into neural circuits inside the retina. After uncovering a new type of retinal cell and mapping how the retina deals with colours, the team from Santa Cruz (US), Krakow and Glasgow is now turning its attention to more complex issues such as how the retina gets wired up and how the brain deals with the signals it receives from the retina. All this using technology derived from high-density, multistrip silicon detectors…   Seen from the point of view of a particle physicist, eyes are image detectors that can gather many different types of data: light and dark, different colours, motion, etc. In particular, the retina, a thin tissue that lines the back of the eye, is a biological pixel detector that detects light and converts it to electrical signals that travel through the optic nerve to the brain. Neurobiologists know that many different cell types are involved in these processes, but they...

  9. Circuitry for a Wireless Microsystem for Neural Recording Microprobes

    National Research Council Canada - National Science Library

    Yu, Hao

    2001-01-01

    .... Recorded neural signals are amplified, multiplexed, digitized using a 2nd order sigma-delta modulator, and then transmitted to the outside world by an on-chip transmitter, The circuit is designed using a standard...

  10. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    Science.gov (United States)

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  11. The Neural Circuitry of Expertise: Perceptual Learning and Social Cognition

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    Michael eHarre

    2013-12-01

    Full Text Available Amongst the most significant questions we are confronted with today include the integration of the brain's micro-circuitry, our ability to build the complex social networks that underpin society and how our society impacts on our ecological environment. In trying to unravel these issues one place to begin is at the level of the individual: to consider how we accumulate information about our environment, how this information leads to decisions and how our individual decisions in turn create our social environment. While this is an enormous task, we may already have at hand many of the tools we need. This article is intended to review some of the recent results in neuro-cognitive research and show how they can be extended to two very specific types of expertise: perceptual expertise and social cognition. These two cognitive skills span a vast range of our genetic heritage. Perceptual expertise developed very early in our evolutionary history and is likely a highly developed part of all mammals' cognitive ability. On the other hand social cognition is most highly developed in humans in that we are able to maintain larger and more stable long term social connections with more behaviourally diverse individuals than any other species. To illustrate these ideas I will discuss board games as a toy model of social interactions as they include many of the relevant concepts: perceptual learning, decision-making, long term planning and understanding the mental states of other people. Using techniques that have been developed in mathematical psychology, I show that we can represent some of the key features of expertise using stochastic differential equations. Such models demonstrate how an expert's long exposure to a particular context influences the information they accumulate in order to make a decision.These processes are not confined to board games, we are all experts in our daily lives through long exposure to the many regularities of daily tasks and

  12. The neural circuitry of expertise: perceptual learning and social cognition.

    Science.gov (United States)

    Harré, Michael

    2013-12-17

    Amongst the most significant questions we are confronted with today include the integration of the brain's micro-circuitry, our ability to build the complex social networks that underpin society and how our society impacts on our ecological environment. In trying to unravel these issues one place to begin is at the level of the individual: to consider how we accumulate information about our environment, how this information leads to decisions and how our individual decisions in turn create our social environment. While this is an enormous task, we may already have at hand many of the tools we need. This article is intended to review some of the recent results in neuro-cognitive research and show how they can be extended to two very specific and interrelated types of expertise: perceptual expertise and social cognition. These two cognitive skills span a vast range of our genetic heritage. Perceptual expertise developed very early in our evolutionary history and is a highly developed part of all mammals' cognitive ability. On the other hand social cognition is most highly developed in humans in that we are able to maintain larger and more stable long term social connections with more behaviorally diverse individuals than any other species. To illustrate these ideas I will discuss board games as a toy model of social interactions as they include many of the relevant concepts: perceptual learning, decision-making, long term planning and understanding the mental states of other people. Using techniques that have been developed in mathematical psychology, I show that we can represent some of the key features of expertise using stochastic differential equations (SDEs). Such models demonstrate how an expert's long exposure to a particular context influences the information they accumulate in order to make a decision.These processes are not confined to board games, we are all experts in our daily lives through long exposure to the many regularities of daily tasks and social

  13. Neural Circuitry Based on Single Electron Transistors and Single Electron Memories

    Directory of Open Access Journals (Sweden)

    Aïmen BOUBAKER

    2014-05-01

    Full Text Available In this paper, we propose and explain a neural circuitry based on single electron transistors ‘SET’ which can be used in classification and recognition. We implement, after that, a Winner-Take-All ‘WTA’ neural network with lateral inhibition architecture. The original idea of this work is reflected, first, in the proposed new single electron memory ‘SEM’ design by hybridising two promising Single Electron Memory ‘SEM’ and the MTJ/Ring memory and second, in modeling and simulation results of neural memory based on SET. We prove the charge storage in quantum dot in two types of memories.

  14. Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder.

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    Beauregard, Mario; Paquette, Vincent; Lévesque, Johanne

    2006-05-29

    An inability to self-regulate negative emotions appears to play a pivotal role in the genesis of major depressive disorder. This inability may be related to a dysfunction of the neural circuitry underlying emotional self-regulation. This functional magnetic resonance imaging study was conducted to test this hypothesis. Depressed individuals and controls were scanned while they attempted to voluntarily down-regulate sad feelings. The degree of difficulty experienced during down-regulation of sadness was higher in depressed individuals. Furthermore, there was greater activation in the right dorsal anterior cingulate cortex, right anterior temporal pole, right amygdala, and right insula in depressed individuals. These results suggest that emotional dysregulation in major depressive disorder is related to a disturbance in the neural circuitry of emotional self-regulation.

  15. Neural circuitry of impulsivity in a cigarette craving paradigm

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    Josiane eBourque

    2013-07-01

    Full Text Available Impulsivity has been shown to play a pivotal role in the onset, pattern of consumption, relapse and, most notably, craving of illicit and licit drugs such as cigarette smoking. The goal of this study was to examine the neurobiological influence of trait impulsivity during cue-induced cigarette craving. Thirty-one chronic smokers passively viewed appetitive smoking-related and neutral images while being scanned and reported their feelings of craving. They completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. We conducted functional connectivity analyses using the psycho-physiological interaction method. During the processing of smoking stimuli, participants presented increased activations in the cingulate and prefrontal cortices, as well as in the limbic system. We observed a significant positive relationship between impulsivity scores and reported craving. A negative correlation was observed between the impulsivity score and activity in the posterior cingulate cortex (PCC. The insula, dorsal anterior cingulate cortex (dACC as well as the dorsolateral prefrontal cortex (DLPFC presented a negative connectivity with the PCC. Consistent with the view that the PCC is related to the ability to resist cigarette craving, our results suggest that high impulsive smokers have greater difficulty in controlling their cravings, and that this weakness may be mediated by lower PCC activity. Moreover, we argue that the less PCC activity, the greater the probability of a stronger emotional, physiological and biased attentional response to smoking cues mediated by insula, dACC and DLPFC activity. This is the first study on this topic, and so, results will need to be replicated in both licit and illicit drug abusers. Our findings also highlight a need for more emphasis on the PCC in drug addiction research, as it is one of the most consistently activated regions in fMRI studies examining the neural correlates of cue-induced alcohol, drug and

  16. Impulsivity and aggression in schizophrenia: a neural circuitry perspective with implications for treatment.

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    Hoptman, Matthew J

    2015-06-01

    Elevations of impulsive behavior have been observed in a number of serious mental illnesses. These phenomena can lead to harmful behaviors, including violence, and thus represent a serious public health concern. Such violence is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Despite the attention paid to violence, little is understood about its neural basis in schizophrenia. On a psychological level, aggression in schizophrenia has been primarily attributed to psychotic symptoms, desires for instrumental gain, or impulsive responses to perceived personal slights. Often, multiple attributions can coexist during a single aggressive incident. In this review, I discuss the neural circuitry associated with impulsivity and aggression in schizophrenia, with an emphasis on implications for treatment. Impulsivity appears to account for a great deal of aggression in schizophrenia, especially in inpatient settings. Urgency, defined as impulsivity in the context of strong emotion, is the primary focus of this article. It is elevated in several psychiatric disorders, and in schizophrenia, it has been related to aggression. Many studies have implicated dysfunctional frontotemporal circuitry in impulsivity and aggression in schizophrenia, and pharmacological treatments may act via that circuitry to reduce urgency and aggressive behaviors; however, more mechanistic studies are critically needed. Recent studies point toward manipulable neurobehavioral targets and suggest that cognitive, pharmacological, neuromodulatory, and neurofeedback treatment approaches can be developed to ameliorate urgency and aggression in schizophrenia. It is hoped that these approaches will improve treatment efficacy.

  17. The emotional power of poetry: neural circuitry, psychophysiology and compositional principles.

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    Wassiliwizky, Eugen; Koelsch, Stefan; Wagner, Valentin; Jacobsen, Thomas; Menninghaus, Winfried

    2017-08-01

    It is a common experience-and well established experimentally-that music can engage us emotionally in a compelling manner. The mechanisms underlying these experiences are receiving increasing scrutiny. However, the extent to which other domains of aesthetic experience can similarly elicit strong emotions is unknown. Using psychophysiology, neuroimaging and behavioral responses, we show that recited poetry can act as a powerful stimulus for eliciting peak emotional responses, including chills and objectively measurable goosebumps that engage the primary reward circuitry. Importantly, while these responses to poetry are largely analogous to those found for music, their neural underpinnings show important differences, specifically with regard to the crucial role of the nucleus accumbens. We also go beyond replicating previous music-related studies by showing that peak aesthetic pleasure can co-occur with physiological markers of negative affect. Finally, the distribution of chills across the trajectory of poems provides insight into compositional principles of poetry. © The Author (2017). Published by Oxford University Press.

  18. Beautiful friendship: Social sharing of emotions improves subjective feelings and activates the neural reward circuitry.

    Science.gov (United States)

    Wagner, Ullrich; Galli, Lisa; Schott, Björn H; Wold, Andrew; van der Schalk, Job; Manstead, Antony S R; Scherer, Klaus; Walter, Henrik

    2015-06-01

    Humans have a strong tendency to affiliate with other people, especially in emotional situations. Here, we suggest that a critical mechanism underlying this tendency is that socially sharing emotional experiences is in itself perceived as hedonically positive and thereby contributes to the regulation of individual emotions. We investigated the effect of social sharing of emotions on subjective feelings and neural activity by having pairs of friends view emotional (negative and positive) and neutral pictures either alone or with the friend. While the two friends remained physically separated throughout the experiment-with one undergoing functional magnetic resonance imaging and the other performing the task in an adjacent room-they were made aware on a trial-by-trial basis whether they were seeing pictures simultaneously with their friend (shared) or alone (unshared). Ratings of subjective feelings were improved significantly when participants viewed emotional pictures together than alone, an effect that was accompanied by activity increase in ventral striatum and medial orbitofrontal cortex, two important components of the reward circuitry. Because these effects occurred without any communication or interaction between the friends, they point to an important proximate explanation for the basic human motivation to affiliate with others, particularly in emotional situations. © The Author (2014). Published by Oxford University Press.

  19. Sleep-wake disturbances in common neurodegenerative diseases: a closer look at selected aspects of the neural circuitry.

    Science.gov (United States)

    Zhong, George; Naismith, Sharon Linda; Rogers, Naomi Louise; Lewis, Simon John Geoffrey

    2011-08-15

    There is a growing appreciation regarding the relationship between common neurodegenerative diseases, such as Alzheimer's and Parkinson's and sleep-wake disturbances. These clinical features often herald the onset of such conditions and certainly appear to influence disease phenotype and progression. This article reviews some of the pathophysiological processes underlying specific disruptions within the neural circuitry underlying sleep-wake disturbances and explores how clinicopathological relationships commonly manifest. It is proposed that a greater understanding of these relationships should allow insights in to the efficacy of currently available treatments and help in the development of future therapies targeting disruptions within the sleep-wake neural circuitry. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans.

    NARCIS (Netherlands)

    Hermans, E.J.; Ramsey, N.F.; Honk, J van

    2008-01-01

    BACKGROUND: In a range of species, the androgen steroid testosterone is known to potentiate neural circuits involved in intraspecific aggression. Disorders of impulsive aggression in humans have likewise been associated with high testosterone levels, but human evidence for the link between

  1. Effects of direct social experience on trust decisions and neural reward circuitry

    Directory of Open Access Journals (Sweden)

    Dominic S. Fareri

    2012-10-01

    Full Text Available The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner’s moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball tossing game with three fictional partners manipulated to be perceived as good, bad or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants’ trust decisions were influenced by their prior experience in the ball tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction-error (PE learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning

  2. Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

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    Chai Bryan

    2012-10-01

    Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

  3. A Role for the Lateral Dorsal Tegmentum in Memory and Decision Neural Circuitry

    Science.gov (United States)

    Redila, Van; Kinzel, Chantelle; Jo, Yong Sang; Puryear, Corey B.; Mizumori, Sheri J.Y.

    2017-01-01

    A role for the hippocampus in memory is clear, although the mechanism for its contribution remains a matter of debate. Converging evidence suggests that hippocampus evaluates the extent to which context-defining features of events occur as expected. The consequence of mismatches, or prediction error, signals from hippocampus is discussed in terms of its impact on neural circuitry that evaluates the significance of prediction errors: Ventral tegmental area (VTA) dopamine cells burst fire to rewards or cues that predict rewards (Schultz et al., 1997). Although the lateral dorsal tegmentum (LDTg) importantly controls dopamine cell burst firing (Lodge & Grace, 2006) the behavioral significance of the LDTg control is not known. Therefore, we evaluated LDTg functional activity as rats performed a spatial memory task that generates task-dependent reward codes in VTA (Jo et al., 2013; Puryear et al., 2010) and another VTA afferent, the pedunculopontine nucleus (PPTg, Norton et al., 2011). Reversible inactivation of the LDTg significantly impaired choice accuracy. LDTg neurons coded primarily egocentric information in the form of movement velocity, turning behaviors, and behaviors leading up to expected reward locations. A subset of the velocity-tuned LDTg cells also showed high frequency bursts shortly before or after reward encounters, after which they showed tonic elevated firing during consumption of small, but not large, rewards. Cells that fired before reward encounters showed stronger correlations with velocity as rats moved toward, rather than away from, rewarded sites. LDTg neural activity was more strongly regulated by egocentric behaviors than that observed for PPTg or VTA cells that were recorded by Puryear et al. and Norton et al. While PPTg activity was uniquely sensitive to ongoing sensory input, all three regions encoded reward magnitude (although in different ways), reward expectation, and reward encounters. Only VTA encoded reward prediction errors. LDTg

  4. Central neural circuitry in the jellyfish Aglantha: a model 'simple nervous system'.

    Science.gov (United States)

    Mackie, George O

    2004-01-01

    Like other hydrozoan medusae, Aglantha lacks a brain, but the two marginal nerve rings function together as a central nervous system. Twelve neuronal and two excitable epithelial conduction systems are described and their interactions summarized. Aglantha differs from most medusae in having giant axons. It can swim and contract its tentacles in two distinct ways (escape and slow). Escape responses are mediated primarily by giant axons but conventional interneurons are also involved in transmission of information within the nerve rings during one form of escape behavior. Surprisingly, giant axons provide the motor pathway to the swim muscles in both escape and slow swimming. This is possible because these axons can conduct calcium spikes as well as sodium spikes and do so on an either/or basis without overlap. The synaptic and ionic bases for these responses are reviewed. During feeding, the manubrium performs highly accurate flexions to points at the margin. At the same time, the oral lips flare open. The directional flexions are conducted by FMRFamide immunoreactive nerves, the lip flaring by an excitable epithelium lining the radial canals. Inhibition of swimming during feeding is due to impulses propagated centrifugally in the same epithelium. Aglantha probably evolved from an ancestor possessing a relatively simple wiring plan, as seen in other hydromedusae. Acquisition of giant axons resulted in considerable modification of this basic plan, and required novel solutions to the problems of integrating escape with non-escape circuitry. Copyright 2004 S. Karger AG, Basel

  5. In Vitro Restoration of an Amyloid-Beta Altered Network Circuitry in a 'Mutated Biomimetic Acetylcholinesterase' Memristor/Memcapacitor Neural Prosthesis

    Directory of Open Access Journals (Sweden)

    John THORNTON

    2015-08-01

    Full Text Available Many diseases involve the ysregulation of acetylcholinesterase (ACHE causing inappropriate production of the neurotransmitter acetylcholine (ACH. Study of how the ACH actually restores a life threatening neural circuitry damage will provide valuable information for study Alzhermer’s disease. An artificial neuronal device was developed with nanostructured biomimetic mutated ACHE gorge membrane on gold chips having memristor/memcapacitor’s characteristics, served as a model for damaged brain circuitry prosthesis, compared before and after ACH treatments, for in vitro evaluation of the memory restoration in the presence of Amyloid-beta (Ab under the conditions of free from tracers and antibodies in NIST human serum. The results are presented in three categories in “Energy-Sensory” images. Before ACH treatments, images showed four stages of circuitry damages from non symptomatic to life threatening. After a 15 nM ACH treatment, the circuitry was restored due to the ACH removed Pathological High Frequency Oscillation (pHFO center during Slow- Waving Sleeping (SWS. After the prosthesis increased hydrophobicity, the High Frequency Oscillation (HFO was created. Results were compared between the recovered and the “normal brain”: 0.14 vs. 0.47 pJ/bit/µm3 for long-term and 14.0 vs.7.0 aJ/bit/µm3 for short-term memory restoration, respectively. The ratio of Rmax/Rmin value is 6.3-fold higher after the treatment of ACH compared without the treatment in the presence of Ab and the reentry sensitivity increased by 613.8- fold.

  6. Neural circuitry of emotion regulation: Effects of appraisal, attention, and cortisol administration.

    Science.gov (United States)

    Ma, Sean T; Abelson, James L; Okada, Go; Taylor, Stephan F; Liberzon, Israel

    2017-04-01

    Psychosocial well-being requires effective regulation of emotional responding in context of threat or stress. Neuroimaging studies have focused on instructed, volitional regulation (e.g., reappraisal or distancing), largely ignoring implicit regulation that does not involve purposeful effort to alter emotional experience. These implicit processes may or may not involve the same neural pathways as explicit regulatory strategies. We examined the neurobiology of implicit emotional regulation processes and the impact of the stress hormone cortisol on these processes. Our study task employed composite pictures of faces and places to examine neural activity during implicit emotional processing (of emotional faces), while these responses were implicitly regulated by attention shift away from the emotionally evocative stimuli, and while subjects reflectively appraised their own emotional response to them. Subjects completed the task in an fMRI scanner after random assignment to receive placebo or hydrocortisone (HCT), an orally administered version of cortisol. Implicit emotional processing activated insula/IFG, dACC/dMPFC, midbrain and amygdala. With attention shifting, we saw diminished signal in emotion generating/response regions (e.g., amygdala) and increased activations in task specific attention regions like parahippocampus. With appraisal of emotions, we observed robust activations in medial prefrontal areas, where activation is also seen in instructed reappraisal studies. We observed no main effects of HCT administration on brain, but males and females showed opposing neural effects in prefrontal areas. The data suggest that different types of emotion regulation utilize overlapping circuits, but with some strategy specific activation. Further study of the dimorphic sex response to cortisol is needed.

  7. Neural emotion regulation circuitry underlying anxiolytic effects of perceived control over pain.

    Science.gov (United States)

    Salomons, Tim V; Nusslock, Robin; Detloff, Allison; Johnstone, Tom; Davidson, Richard J

    2015-02-01

    Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within-subject designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neural and affective responses when participants were exposed to either uncontrollable or controllable stress, two groups of participants received an identical series of stressors (thermal pain stimuli). One group ("controllable") was led to believe they had behavioral control over the pain stimuli, whereas another ("uncontrollable") believed they had no control. Controllable pain was associated with decreased state anxiety, decreased activation in amygdala, and increased activation in nucleus accumbens. In participants who perceived control over the pain, reduced state anxiety was associated with increased functional connectivity between each of these regions and ventral lateral/ventral medial pFC. The location of pFC findings is consistent with regions found to be critical for the anxiolytic effects of perceived control in rodents. Furthermore, interactions observed between pFC and both amygdala and nucleus accumbens are remarkably similar to neural mechanisms of emotion regulation through reappraisal in humans. These results suggest that perceived control reduces negative affect through a general mechanism involved in the cognitive regulation of emotion.

  8. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

    Science.gov (United States)

    Phillips, Mary L; Swartz, Holly A.

    2014-01-01

    Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual

  9. Neural circuitry mediating inflammation-induced central pain amplification in human experimental endotoxemia.

    Science.gov (United States)

    Benson, Sven; Rebernik, Laura; Wegner, Alexander; Kleine-Borgmann, Julian; Engler, Harald; Schlamann, Marc; Forsting, Michael; Schedlowski, Manfred; Elsenbruch, Sigrid

    2015-08-01

    To elucidate the brain mechanisms underlying inflammation-induced visceral hyperalgesia in humans, in this functional magnetic resonance imaging (fMRI) study we tested if intravenous administration of lipopolysaccharide (LPS) involves altered central processing of visceral pain stimuli. In this randomized, double-blind, placebo-controlled fMRI study, 26 healthy male subjects received either an intravenous injection of low-dose LPS (N=14, 0.4 ng/kg body weight) or placebo (N=12, control group). Plasma cytokines (TNF-α, IL-6), body temperature, plasma cortisol and mood were assessed at baseline and up to 6 h post-injection. At baseline and 2 h post-injection (test), rectal pain thresholds and painful rectal distension-induced blood oxygen level-dependent (BOLD) responses in brain regions-of-interest were assessed. To address specificity for visceral pain, BOLD responses to non-painful rectal distensions and painful somatic stimuli (i.e., punctuate mechanical stimulation) were also analyzed as control stimuli. Compared to the control group, LPS-treated subjects demonstrated significant and transient increases in TNF-α, IL-6, body temperature and cortisol, along with impaired mood. In response to LPS, rectal pain thresholds decreased in trend, along with enhanced up-regulation of rectal pain-induced BOLD responses within the posterior insula, dorsolateral prefrontal (DLPFC), anterior midcingulate (aMCC) and somatosensory cortices (all FWE-corrected ppain-induced neural activation in DLPFC and aMCC. No significant LPS effects were observed on neural responses to non-painful rectal distensions or mechanical stimulation. These findings support that peripheral inflammatory processes affect visceral pain thresholds and the central processing of sensory-discriminative aspects of visceral pain. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder.

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    Briceño, Emily M; Rapport, Lisa J; Kassel, Michelle T; Bieliauskas, Linas A; Zubieta, Jon-Kar; Weisenbach, Sara L; Langenecker, Scott A

    2015-03-01

    Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. Cross-sectional comparison of fMRI signal during performance of an emotion processing task. Outpatient university setting. One hundred adults recruited by MDD status, gender, and age. Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Neural Circuitry of the Bilingual Mental Lexicon: Effect of Age of Second Language Acquisition

    Science.gov (United States)

    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…

  12. Affective neural circuitry during facial emotion processing in pediatric bipolar disorder.

    Science.gov (United States)

    Pavuluri, Mani N; O'Connor, Megan Marlow; Harral, Erin; Sweeney, John A

    2007-07-15

    Facial emotions are central to human interaction. Identifying pathophysiology in affect processing circuitry that supports the ability to assess facial emotions might facilitate understanding of affect regulation in pediatric bipolar disorder. Ten euthymic, unmedicated pediatric bipolar patients and 10 healthy control subjects matched for age, gender, race, socioeconomic status, and IQ were scanned with functional magnetic resonance imaging. Angry, happy, and neutral faces were presented in 30-sec blocks, with a 20-sec rest period between blocks. Subjects were asked to press a button when each face appeared, to ensure that attention was maintained on-task. In bipolar patients, in response to both angry and happy faces relative to neutral faces, we observed reduced activation of right rostral ventrolateral prefrontal cortex together with increased activity in right pregenual anterior cingulate, amygdala, and paralimbic cortex. Bipolar patients also showed reduced activation of visual areas in occipital cortex together with greater activation in higher-order visual perceptual areas, including superior temporal sulcus and fusiform gyrus with angry faces and posterior parietal cortex with happy faces. Findings document a disturbance in affective neurocircuitry in pediatric bipolar disorder. Reduced activation in ventrolateral prefrontal cortex might reflect diminished top-down control that leads to the observed exaggerated activation in amygdala and paralimbic areas. Changes in occipital areas might represent an effort to gate sensory input when affective responses to the faces could not be successfully modulated. Disturbances in affect processing circuitry could contribute to emotional dysregulation and social cognitive difficulties in bipolar youth.

  13. Carbohydrate in the mouth enhances activation of brain circuitry involved in motor performance and sensory perception.

    Science.gov (United States)

    Turner, Clare E; Byblow, Winston D; Stinear, Cathy M; Gant, Nicholas

    2014-09-01

    The presence of carbohydrate in the human mouth has been associated with the facilitation of motor output and improvements in physical performance. Oral receptors have been identified as a potential mode of afferent transduction for this novel form of nutrient signalling that is distinct from taste. In the current study oral exposure to carbohydrate was combined with a motor task in a neuroimaging environment to identify areas of the brain involved in this phenomenon. A mouth-rinsing protocol was conducted whilst carbohydrate (CHO) and taste-matched placebo (PLA) solutions were delivered and recovered from the mouths of 10 healthy volunteers within a double-blind, counterbalanced design. This protocol eliminates post-oral factors and controls for the perceptual qualities of solutions. Functional magnetic resonance imaging of the brain was used to identify cortical areas responsive to oral carbohydrate during rest and activity phases of a hand-grip motor task. Mean blood-oxygen-level dependent signal change experienced in the contralateral primary sensorimotor cortex was larger for CHO compared with PLA during the motor task when contrasted with a control condition. Areas of activation associated with CHO exclusively were observed over the primary taste cortex and regions involved in visual perception. Regions in the limbic system associated with reward were also significantly more active with CHO. This is the first demonstration that oral carbohydrate signalling can increase activation within the primary sensorimotor cortex during physical activity and enhance activation of neural networks involved in sensory perception. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Role of basal ganglia in sleep-wake regulation: neural circuitry and clinical significance

    Directory of Open Access Journals (Sweden)

    Ramalingam Vetrivelan

    2010-11-01

    Full Text Available Researchers over the last decade have made substantial progress towards understanding the roles of dopamine and the basal ganglia in the control of sleep-wake behavior. In this review, we outline recent advancements regarding dopaminergic modulation of sleep through the basal ganglia (BG and extra-BG sites. Our main hypothesis is that dopamine promotes sleep by its action on the D2 receptors in the BG and promotes wakefulness by its action on D1 and D2 receptors in the extra-BG sites. This hypothesis implicates dopamine depletion in the BG (such as in Parkinson’s disease in causing frequent nighttime arousal and overall insomnia. Furthermore, the arousal effects of psychostimulants (methamphetamine, cocaine and modafinil may be linked to the ventral periaquductal grey (vPAG dopaminergic circuitry targeting the extra-BG sleep-wake network.

  15. Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise.

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    Antoine Lutz

    2008-03-01

    Full Text Available Recent brain imaging studies using functional magnetic resonance imaging (fMRI have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices during meditation (versus rest. During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ, and right posterior superior temporal sulcus (pSTS in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in

  16. Neural circuitry of the bilingual mental lexicon: effect of age of second language acquisition.

    Science.gov (United States)

    Isel, Frédéric; Baumgaertner, Annette; Thrän, Johannes; Meisel, Jürgen M; Büchel, Christian

    2010-03-01

    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 lexical knowledge in L2 is available. The present functional magnetic resonance study addresses this question via a cross-linguistic neural adaptation paradigm. Age of acquisition (AoA) of L2 was systematically manipulated. Concrete nouns were repeated across language (e.g., French-German, valise(suitcase)-Koffer(suitcase)). Whereas early bilinguals (AoA of L210years) showed larger RE effects in the middle portion of the left insula and in the right middle frontal gyrus (MFG). We suggest that, as for grammatical knowledge, the attainment of lexical knowledge in L2 is affected by neural maturation. The present findings lend support to neurocognitive models of bilingual word recognition postulating that, for both early and late bilinguals, the two languages are interconnected at the conceptual level. Copyright 2009 Elsevier Inc. All rights reserved.

  17. On the connection between level of education and the neural circuitry of emotion perception

    NARCIS (Netherlands)

    Demenescu, L.R.; Stan, A.; Kortekaas, R.; van der Wee, N.J.A.; Veltman, D.J.; Aleman, A.

    2014-01-01

    Through education, a social group transmits accumulated knowledge, skills, customs, and values to its members. So far, to the best of our knowledge, the association between educational attainment and neural correlates of emotion processing has been left unexplored. In a retrospective analysis of The

  18. On the connection between level of education and the neural circuitry of emotion perception

    Directory of Open Access Journals (Sweden)

    Liliana Ramona Demenescu

    2014-10-01

    Full Text Available Through education, a social group transmits accumulated knowledge, skills, customs, and values to its members. So far, to the best of our knowledge, the association between educational attainment and neural correlates of emotion processing has been left unexplored. In a retrospective analysis of the NESDA fMRI study, we compared two groups of fourteen healthy volunteers with intermediate and high educational attainment, matched for age and gender. The data concerned event-related functional magnetic resonance imaging of brain activation during perception of facial emotional expressions. The region of interest analysis showed stronger right amygdala activation to facial expressions in participants with lower relative to higher educational attainment. The psychophysiological interaction analysis revealed that participants with higher educational attainment exhibited stronger right amygdala – right insula connectivity during perception of emotional and neutral facial expressions. This exploratory study suggests the relevance of educational attainment on the neural mechanism of facial expression processing.

  19. Impulsivity and Aggression in Schizophrenia: A Neural Circuitry Perspective with Implications for Treatment

    OpenAIRE

    Hoptman, Matthew J.

    2015-01-01

    Elevations of impulsive behavior have been observed in a number of serious mental illnesses. These phenomena can lead to harmful behaviors, including violence, and thus represent a serious public health concern. Such violence is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Despite the attention paid to violence, little is understood about its neural basis in schizophrenia....

  20. Tracing 'driver' versus 'modulator' information flow throughout large-scale, task-related neural circuitry.

    Science.gov (United States)

    Hermer-Vazquez, Linda

    2008-04-01

    PRIMARY OBJECTIVE: To determine the relative uses of neural action potential ('spike') data versus local field potentials (LFPs) for modeling information flow through complex brain networks. HYPOTHESIS: The common use of LFP data, which are continuous and therefore more mathematically suited for spectral information-flow modeling techniques such as Granger causality analysis, can lead to spurious inferences about whether a given brain area 'drives' the spiking in a downstream area. EXPERIMENT: We recorded spikes and LFPs from the forelimb motor cortex (M1) and the magnocellular red nucleus (mRN), which receives axon collaterals from M1 projection cells onto its distal dendrites, but not onto its perisomatic regions, as rats performed a skilled reaching task. RESULTS AND IMPLICATIONS: As predicted, Granger causality analysis on the LFPs-which are mainly composed of vector-summed dendritic currents-produced results that if conventionally interpreted would suggest that the M1 cells drove spike firing in the mRN, whereas analyses of spiking in the two recorded regions revealed no significant correlations. These results suggest that mathematical models of information flow should treat the sampled dendritic activity as more likely to reflect intrinsic dendritic and input-related processing in neural networks, whereas spikes are more likely to provide information about the output of neural network processing.

  1. A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

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    Salvatore Fusco

    2016-02-01

    Full Text Available Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis.

  2. Dopamine Prediction Errors in Reward Learning and Addiction: From Theory to Neural Circuitry.

    Science.gov (United States)

    Keiflin, Ronald; Janak, Patricia H

    2015-10-21

    Midbrain dopamine (DA) neurons are proposed to signal reward prediction error (RPE), a fundamental parameter in associative learning models. This RPE hypothesis provides a compelling theoretical framework for understanding DA function in reward learning and addiction. New studies support a causal role for DA-mediated RPE activity in promoting learning about natural reward; however, this question has not been explicitly tested in the context of drug addiction. In this review, we integrate theoretical models with experimental findings on the activity of DA systems, and on the causal role of specific neuronal projections and cell types, to provide a circuit-based framework for probing DA-RPE function in addiction. By examining error-encoding DA neurons in the neural network in which they are embedded, hypotheses regarding circuit-level adaptations that possibly contribute to pathological error signaling and addiction can be formulated and tested. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. When the Sense of Smell Meets Emotion: Anxiety-State-Dependent Olfactory Processing and Neural Circuitry Adaptation

    Science.gov (United States)

    Novak, Lucas R.; Gitelman, Darren R.

    2013-01-01

    Phylogenetically the most ancient sense, olfaction is characterized by a unique intimacy with the emotion system. However, mechanisms underlying olfaction–emotion interaction remain unclear, especially in an ever-changing environment and dynamic internal milieu. Perturbing the internal state with anxiety induction in human subjects, we interrogated emotion-state-dependent olfactory processing in a functional magnetic resonance imaging (fMRI) study. Following anxiety induction, initially neutral odors become unpleasant and take longer to detect, accompanied by augmented response to these odors in the olfactory (anterior piriform and orbitofrontal) cortices and emotion-relevant pregenual anterior cingulate cortex. In parallel, the olfactory sensory relay adapts with increased anxiety, incorporating amygdala as an integral step via strengthened (afferent or efferent) connections between amygdala and all levels of the olfactory cortical hierarchy. This anxiety-state-dependent neural circuitry thus enables cumulative infusion of limbic affective information throughout the olfactory sensory progression, thereby driving affectively charged olfactory perception. These findings could constitute an olfactory etiology model of emotional disorders, as exaggerated emotion–olfaction interaction in negative mood states turns innocuous odors aversive, fueling anxiety and depression with rising ambient sensory stress. PMID:24068799

  4. Food-Related Neural Circuitry in Prader-Willi Syndrome: Response to High- versus Low-Calorie Foods

    Science.gov (United States)

    Dimitropoulos, Anastasia; Schultz, Robert T.

    2008-01-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hyperphagia and food preoccupations. Although dysfunction of the hypothalamus likely has a critical role in hyperphagia, it is only one of several regions involved in the regulation of eating. The purpose of this research was to examine food-related neural circuitry…

  5. Neural Circuitry That Mediates Behavior Governing the Tradeoffs Between Survival and Reproduction in Caenorhabditis elegans.

    Science.gov (United States)

    Emmons, Scott W

    2017-12-01

    In all outcrossing sexual species there is a mechanism that brings two parents together. For animals, this reproductive requirement may at times conflict with other needs, such as foraging for food. This tension has been studied using the tiny (1 mm) nematode worm, Caenorhabditis elegans. In a trade off between certainty of survival and possibility of reproduction, the C. elegans male will abandon a food patch lacking mates and explore its environment to find one where mates are present. A quantitative behavioral assay has been used to study the behavioral mechanism of mate searching and nutritional, sexual, and neurohormonal pathways that influence the underlying drive state. Taking advantage of the known connectivity of the C. elegans nervous system, neural pathways have been identified that influence the male's behavior in the presence of food with and without mates. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  6. Overlapping neural circuitry for narrative comprehension and proficient reading in children and adolescents.

    Science.gov (United States)

    Horowitz-Kraus, Tzipi; Vannest, Jennifer J; Holland, Scott K

    2013-11-01

    Narrative comprehension is a perinatal linguistic ability which is more intuitive than reading activity. Whether there are specific shared brain regions for narrative comprehension and reading that are tuned to reading proficiency, even before reading is acquired, is the question of the current study. We acquired fMRI data during a narrative comprehension task at two age points, when children are age 5-7 (K-2nd grade) and later when the same children were age 11 (5th-7th grade). We then examined correlations between this fMRI data and reading and reading comprehension scores from the same children at age 11. We found that greater frontal and supramarginal gyrus (BA 40) activation in narrative comprehension at the age of 5-7 years old was associated with better word reading and reading comprehension scores at the age of 11. A shift towards temporal and occipital activation was found when correlating their narrative comprehension functional data at age 11, with reading scores at the same age point. We suggest that increased reliance on executive functions and auditory-visual networks when listening to stories before reading is acquired, facilitates reading proficiency in older age and may be a biomarker for future reading ability. Children, who rely on use of imagination/visualization as well as auditory processing for narrative comprehension when they reach age 11, also show greater reading abilities. Understanding concordant neural pathways supporting auditory narrative and reading comprehension might be guide for development of effective tools for reading intervention programs. Published by Elsevier Ltd.

  7. Memory trace in feeding neural circuitry underlying conditioned taste aversion in Lymnaea.

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    Etsuro Ito

    Full Text Available BACKGROUND: The pond snail Lymnaea stagnalis can maintain a conditioned taste aversion (CTA as a long-term memory. Previous studies have shown that the inhibitory postsynaptic potential (IPSP evoked in the neuron 1 medial (N1M cell by activation of the cerebral giant cell (CGC in taste aversion-trained snails was larger and lasted longer than that in control snails. The N1M cell is one of the interneurons in the feeding central pattern generator (CPG, and the CGC is a key regulatory neuron for the feeding CPG. METHODOLOGY/PRINCIPLE FINDINGS: Previous studies have suggested that the neural circuit between the CGC and the N1M cell consists of two synaptic connections: (1 the excitatory connection from the CGC to the neuron 3 tonic (N3t cell and (2 the inhibitory connection from the N3t cell to the N1M cell. However, because the N3t cell is too small to access consistently by electrophysiological methods, in the present study the synaptic inputs from the CGC to the N3t cell and those from the N3t cell to the N1M cell were monitored as the monosynaptic excitatory postsynaptic potential (EPSP recorded in the large B1 and B3 motor neurons, respectively. The evoked monosynaptic EPSPs of the B1 motor neurons in the brains isolated from the taste aversion-trained snails were identical to those in the control snails, whereas the spontaneous monosynaptic EPSPs of the B3 motor neurons were significantly enlarged. CONCLUSION/SIGNIFICANCE: These results suggest that, after taste aversion training, the monosynaptic inputs from the N3t cell to the following neurons including the N1M cell are specifically facilitated. That is, one of the memory traces for taste aversion remains as an increase in neurotransmitter released from the N3t cell. We thus conclude that the N3t cell suppresses the N1M cell in the feeding CPG, in response to the conditioned stimulus in Lymnaea CTA.

  8. Neural circuitry at age 6 months associated with later repetitive behavior and sensory responsiveness in autism.

    Science.gov (United States)

    Wolff, Jason J; Swanson, Meghan R; Elison, Jed T; Gerig, Guido; Pruett, John R; Styner, Martin A; Vachet, Clement; Botteron, Kelly N; Dager, Stephen R; Estes, Annette M; Hazlett, Heather C; Schultz, Robert T; Shen, Mark D; Zwaigenbaum, Lonnie; Piven, Joseph

    2017-01-01

    Restricted and repetitive behaviors are defining features of autism spectrum disorder (ASD). Under revised diagnostic criteria for ASD, this behavioral domain now includes atypical responses to sensory stimuli. To date, little is known about the neural circuitry underlying these features of ASD early in life. Longitudinal diffusion tensor imaging data were collected from 217 infants at high familial risk for ASD. Forty-four of these infants were diagnosed with ASD at age 2. Targeted cortical, cerebellar, and striatal white matter pathways were defined and measured at ages 6, 12, and 24 months. Dependent variables included the Repetitive Behavior Scale-Revised and the Sensory Experiences Questionnaire. Among children diagnosed with ASD, repetitive behaviors and sensory response patterns were strongly correlated, even when accounting for developmental level or social impairment. Longitudinal analyses indicated that the genu and cerebellar pathways were significantly associated with both repetitive behaviors and sensory responsiveness but not social deficits. At age 6 months, fractional anisotropy in the genu significantly predicted repetitive behaviors and sensory responsiveness at age 2. Cerebellar pathways significantly predicted later sensory responsiveness. Exploratory analyses suggested a possible disordinal interaction based on diagnostic status for the association between fractional anisotropy and repetitive behavior. Our findings suggest that restricted and repetitive behaviors contributing to a diagnosis of ASD at age 2 years are associated with structural properties of callosal and cerebellar white matter pathways measured during infancy and toddlerhood. We further identified that repetitive behaviors and unusual sensory response patterns co-occur and share common brain-behavior relationships. These results were strikingly specific given the absence of association between targeted pathways and social deficits.

  9. Motor cortex-periaqueductal gray-spinal cord neuronal circuitry may involve in modulation of nociception: a virally mediated transsynaptic tracing study in spinally transected transgenic mouse model.

    Directory of Open Access Journals (Sweden)

    Da-Wei Ye

    Full Text Available Several studies have shown that motor cortex stimulation provided pain relief by motor cortex plasticity and activating descending inhibitory pain control systems. Recent evidence indicated that the melanocortin-4 receptor (MC4R in the periaqueductal gray played an important role in neuropathic pain. This study was designed to assess whether MC4R signaling existed in motor cortex-periaqueductal gray-spinal cord neuronal circuitry modulated the activity of sympathetic pathway by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV-614 was injected into the left gastrocnemius muscle in adult male MC4R-green fluorescent protein (GFP transgenic mice (n = 15. After a survival time of 4-6 days, the mice (n = 5 were randomly assigned to humanely sacrifice, and spinal cords and brains were removed and sectioned, and processed for PRV-614 visualization. Neurons involved in the efferent control of the left gastrocnemius muscle were identified following visualization of PRV-614 retrograde tracing. The neurochemical phenotype of MC4R-GFP-positive neurons was identified using fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons were detected in spinal IML, periaqueductal gray and motor cortex. Our findings support the hypothesis that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may participate in the modulation of the melanocortin-sympathetic signaling and contribute to the descending modulation of nociceptive transmission, suggesting that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may modulate the activity of sympathetic outflow sensitive to nociceptive signals.

  10. Social pain and social gain in the adolescent brain: A common neural circuitry underlying both positive and negative social evaluation

    Science.gov (United States)

    Dalgleish, Tim; Walsh, Nicholas D.; Mobbs, Dean; Schweizer, Susanne; van Harmelen, Anne-Laura; Dunn, Barnaby; Dunn, Valerie; Goodyer, Ian; Stretton, Jason

    2017-01-01

    Social interaction inherently involves the subjective evaluation of cues salient to social inclusion and exclusion. Testifying to the importance of such social cues, parts of the neural system dedicated to the detection of physical pain, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been shown to be equally sensitive to the detection of social pain experienced after social exclusion. However, recent work suggests that this dACC-AI matrix may index any socially pertinent information. We directly tested the hypothesis that the dACC-AI would respond to cues of both inclusion and exclusion, using a novel social feedback fMRI paradigm in a population-derived sample of adolescents. We show that the dACC and left AI are commonly activated by feedback cues of inclusion and exclusion. Our findings suggest that theoretical accounts of the dACC-AI network as a neural alarm system restricted within the social domain to the processing of signals of exclusion require significant revision. PMID:28169323

  11. Neural Correlates of Moral Sensitivity and Moral Judgment Associated with Brain Circuitries of Selfhood: A Meta-Analysis

    Science.gov (United States)

    Han, Hyemin

    2017-01-01

    The present study meta-analyzed 45 experiments with 959 subjects and 463 activation foci reported in 43 published articles that investigated the neural mechanism of moral functions by comparing neural activity between the moral task conditions and non-moral task conditions with the Activation Likelihood Estimation method. The present study…

  12. rsfMRI effects of KB220Z™ on Neural Pathways in Reward Circuitry of Abstinent Genotyped Heroin Addicts

    Science.gov (United States)

    Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S.

    2016-01-01

    Recently Willuhn et al. reported that cocaine use and even non-substance related addictive behavior, increases, as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors, also associated with lower activation to cues in occipital cortex and cerebellum in a recent PET study from Volkow’s group. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of ten heroin addicts undergoing protracted abstinence, an average 16.9 months. In a randomized placebo-controlled crossover study of KB220Z™ five subjects completed a triple blinded–experiment in which the subject, the person administering the treatment and the person evaluating the response to treatment were blinded as to which treatment any particular subject was receiving. In addition, nine subjects total were genotyped utilizing the GARSRX™ test. We preliminarily report that KB220Z ™ induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following one-hour acute administration. Furthermore, KB220Z™ also reduced resting state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all ten abstinent heroin-dependent subjects, three brain regions of interest (ROIs) we observed to be significantly activated from resting state by KB220Z compared to placebo (P addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results and confirmation with additional research and ongoing rodent and human studies of KB220Z, is required. PMID:25526228

  13. The Advantages of Human Milk Recognize the Spatiotemporal Locations of Toxins and Intelligently Bypass Them by Forming a Hummingbird-Like Hovering Neural Network Circuitry Based on an Organic Biomimetic Choline Acetyltransferase Memristor/Memcapacitor Prosthesis

    Directory of Open Access Journals (Sweden)

    E. T. CHEN

    2016-08-01

    Full Text Available We have demonstrated a unique approach to study human milk’s advantage in promoting and protecting infant early brain cognitive development by recognizing toxins and intelligently bypassing the toxin by forming high frequency oscillation (HFO in the brain circuitry when compared with organic cow milk samples based on an organic memristor/memcapacitor biomimetic Choline Acetyltransferase (CHAT neural network circuitry prosthesis along with a 3D Energy-sensory dynamic mapping method under antibody- free, radiolabeling-free, and reagent-less conditions. We also demonstrated cow milk is unfit for infant cognitive development, and it is actually harmful in terms of mutating infant brain synapse circuitry conformation, current flow direction, and energy output that lead to multiple Pathological High Frequency Oscillation (pHFO formations, and further, it led to sudden infant death syndrome (SIDS based on our prediction.

  14. Speed hysteresis and noise shaping of traveling fronts in neural fields: role of local circuitry and nonlocal connectivity

    Science.gov (United States)

    Capone, Cristiano; Mattia, Maurizio

    2017-01-01

    Neural field models are powerful tools to investigate the richness of spatiotemporal activity patterns like waves and bumps, emerging from the cerebral cortex. Understanding how spontaneous and evoked activity is related to the structure of underlying networks is of central interest to unfold how information is processed by these systems. Here we focus on the interplay between local properties like input-output gain function and recurrent synaptic self-excitation of cortical modules, and nonlocal intermodular synaptic couplings yielding to define a multiscale neural field. In this framework, we work out analytic expressions for the wave speed and the stochastic diffusion of propagating fronts uncovering the existence of an optimal balance between local and nonlocal connectivity which minimizes the fluctuations of the activation front propagation. Incorporating an activity-dependent adaptation of local excitability further highlights the independent role that local and nonlocal connectivity play in modulating the speed of propagation of the activation and silencing wavefronts, respectively. Inhomogeneities in space of local excitability give raise to a novel hysteresis phenomenon such that the speed of waves traveling in opposite directions display different velocities in the same location. Taken together these results provide insights on the multiscale organization of brain slow-waves measured during deep sleep and anesthesia.

  15. Layer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia.

    Science.gov (United States)

    Hoftman, Gil D; Datta, Dibyadeep; Lewis, David A

    2017-05-15

    Convergent evidence suggests that schizophrenia is a disorder of neurodevelopment with alterations in both early and late developmental processes hypothesized to contribute to the disease process. Abnormalities in certain clinical features of schizophrenia, such as working memory impairments, depend on distributed neural circuitry including the dorsolateral prefrontal cortex (DLPFC) and appear to arise during the protracted maturation of this circuitry across childhood and adolescence. In particular, the neural circuitry substrate for working memory in primates involves the coordinated activity of excitatory pyramidal neurons and a specific population of inhibitory gamma-aminobutyric acid neurons (i.e., parvalbumin-containing basket cells) in layer 3 of the DLPFC. Understanding the relationships between the normal development of-and the schizophrenia-associated alterations in-the DLPFC circuitry that subserves working memory could provide new insights into the nature of schizophrenia as a neurodevelopmental disorder. Consequently, we review the following in this article: 1) recent findings regarding alterations of DLPFC layer 3 circuitry in schizophrenia, 2) the developmental refinements in this circuitry that occur during the period when the working memory alterations in schizophrenia appear to arise and progress, and 3) how various adverse environmental exposures could contribute to developmental disturbances of this circuitry in individuals with schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Proteus mirabilis abscess involving the entire neural axis.

    Science.gov (United States)

    Kamat, A S; Thango, N S; Husein, M Ben

    2016-08-01

    Intramedullary spinal cord abscesses are rare and potentially devastating lesions usually associated with other infective processes such as bacterial endocarditis, or pulmonary or urogenital infection. We describe a 2-year-old girl who presented with an infected dermal sinus leading to an intraspinal abscess. This abscess eventually spread and involved the entire neural axis leaving her quadriparetic. Drainage of the abscess resulted in recovery and the child regained normal function of her limbs. To our knowledge this is the first documented case of an intramedullary abscess involving the entire neural axis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Baseline Levels of Rapid Eye Movement Sleep May Protect Against Excessive Activity in Fear-Related Neural Circuitry.

    Science.gov (United States)

    Lerner, Itamar; Lupkin, Shira M; Sinha, Neha; Tsai, Alan; Gluck, Mark A

    2017-11-15

    Sleep, and particularly rapid eye movement sleep (REM), has been implicated in the modulation of neural activity following fear conditioning and extinction in both human and animal studies. It has long been presumed that such effects play a role in the formation and persistence of posttraumatic stress disorder, of which sleep impairments are a core feature. However, to date, few studies have thoroughly examined the potential effects of sleep prior to conditioning on subsequent acquisition of fear learning in humans. Furthermore, these studies have been restricted to analyzing the effects of a single night of sleep-thus assuming a state-like relationship between the two. In the current study, we used long-term mobile sleep monitoring and functional neuroimaging (fMRI) to explore whether trait-like variations in sleep patterns, measured in advance in both male and female participants, predict subsequent patterns of neural activity during fear learning. Our results indicate that higher baseline levels of REM sleep predict reduced fear-related activity in, and connectivity between, the hippocampus, amygdala and ventromedial PFC during conditioning. Additionally, skin conductance responses (SCRs) were weakly correlated to the activity in the amygdala. Conversely, there was no direct correlation between REM sleep and SCRs, indicating that REM may only modulate fear acquisition indirectly. In a follow-up experiment, we show that these results are replicable, though to a lesser extent, when measuring sleep over a single night just before conditioning. As such, baseline sleep parameters may be able to serve as biomarkers for resilience, or lack thereof, to trauma. SIGNIFICANCE STATEMENT Numerous studies over the past two decades have established a clear role of sleep in fear-learning processes. However, previous work has focused on the effects of sleep following fear acquisition, thus neglecting the potential effects of baseline sleep levels on the acquisition itself. The

  18. Neural circuitry of masked emotional face processing in youth with bipolar disorder, severe mood dysregulation, and healthy volunteers

    Directory of Open Access Journals (Sweden)

    Laura A. Thomas

    2014-04-01

    Full Text Available Youth with bipolar disorder (BD and those with severe, non-episodic irritability (severe mood dysregulation, SMD show face-emotion labeling deficits. These groups differ from healthy volunteers (HV in neural responses to emotional faces. It is unknown whether awareness is required to elicit these differences. We compared activation in BD (N = 20, SMD (N = 18, and HV (N = 22 during “Aware” and “Non-aware” priming of shapes by emotional faces. Subjects rated how much they liked the shape. In aware, a face (angry, fearful, happy, neutral, blank oval appeared (187 ms before the shape. In non-aware, a face appeared (17 ms, followed by a mask (170 ms, and shape. A Diagnosis-by-Awareness-by-Emotion ANOVA was not significant. There were significant Diagnosis-by-Awareness interactions in occipital regions. BD and SMD showed increased activity for non-aware vs. aware; HV showed the reverse pattern. When subjects viewed angry or neutral faces, there were Emotion-by-Diagnosis interactions in face-emotion processing regions, including the L precentral gyrus, R posterior cingulate, R superior temporal gyrus, R middle occipital gyrus, and L medial frontal gyrus. Regardless of awareness, BD and SMD differ in activation patterns from HV and each other in multiple brain regions, suggesting that BD and SMD are distinct developmental mood disorders.

  19. Emotional reactivity and its impact on neural circuitry for attention–emotion interaction in childhood and adolescence

    Directory of Open Access Journals (Sweden)

    Susan B. Perlman

    2014-04-01

    Full Text Available Attention modulation when confronted with emotional stimuli is considered a critical aspect of executive function, yet rarely studied during childhood and adolescence, a developmental period marked with changes in these processes. We employed a novel, and child-friendly fMRI task that used emotional faces to investigate the neural underpinnings of the attention–emotion interaction in a child and adolescent sample (n = 23, age M = 13.46, SD = 2.86, range = 8.05–16.93 years. Results implied modulation of activation in the orbitofrontal cortex (OFC due to emotional distractor valence, which marginally correlated with participant age. Additionally, parent-reported emotional reactivity predicted the trajectory of BOLD signal increase for fearful emotional face distractors such that participants low in emotional reactivity had a steeper latency to peak activation. Results imply that the use of the OFC to modulate attention in the face of social/emotional stimuli may mature with age and may be tightly coupled with adaptive emotional functioning. Findings are discussed in the context of risk for the development of psychiatric disorders, where increased emotional reactivity is particularly apparent.

  20. Optogenetic mapping of brain circuitry

    Science.gov (United States)

    Augustine, George J.; Berglund, Ken; Gill, Harin; Hoffmann, Carolin; Katarya, Malvika; Kim, Jinsook; Kudolo, John; Lee, Li M.; Lee, Molly; Lo, Daniel; Nakajima, Ryuichi; Park, Min Yoon; Tan, Gregory; Tang, Yanxia; Teo, Peggy; Tsuda, Sachiko; Wen, Lei; Yoon, Su-In

    2012-10-01

    Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.

  1. How plastic are human spinal cord motor circuitries?

    DEFF Research Database (Denmark)

    Christiansen, Lasse; Lundbye-Jensen, Jesper; Perez, Monica A

    2017-01-01

    Human and animal studies have documented that neural circuitries in the spinal cord show adaptive changes caused by altered supraspinal and/or afferent input to the spinal circuitry in relation to learning, immobilization, injury and neurorehabilitation. Reversible adaptations following, e...

  2. Adolescent gain in positive valence of a socially relevant stimulus: engagement of the mesocorticolimbic reward circuitry.

    Science.gov (United States)

    Bell, Margaret R; De Lorme, Kayla C; Figueira, Rayson J; Kashy, Deborah A; Sisk, Cheryl L

    2013-02-01

    A successful transition from childhood to adulthood requires adolescent maturation of social information processing. The neurobiological underpinnings of this maturational process remain elusive. This research employed the male Syrian hamster as a tractable animal model for investigating the neural circuitry involved in this critical transition. In this species, adult and juvenile males display different behavioral and neural responses to vaginal secretions, which contain pheromones essential for expression of sexual behavior in adulthood. These studies tested the hypothesis that vaginal secretions acquire positive valence over adolescent development via remodeling of neural circuits underlying sexual reward. Sexually naïve adult, but not juvenile, hamsters showed a conditioned place preference for vaginal secretions. Differences in behavioral response to vaginal secretions between juveniles and adults correlated with a difference in the vaginal secretion-induced neural activation pattern in mesocorticolimbic reward circuitry. Fos immunoreactivity increased in response to vaginal secretions in the medial amygdala and ventral tegmental dopaminergic cells of both juvenile and adult males. However, only in adults was there a Fos response to vaginal secretions in non-dopaminergic cells in interfascicular ventral tegmental area, nucleus accumbens core and infralimbic medial prefrontal cortex. These results demonstrate that a socially relevant chemosensory stimulus acquires the status of an unconditioned reward during adolescence, and that this adolescent gain in social reward is correlated with experience-independent engagement of specific cell groups in reward circuitry. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  3. Real-time simulation of a spiking neural network model of the basal ganglia circuitry using general purpose computing on graphics processing units.

    Science.gov (United States)

    Igarashi, Jun; Shouno, Osamu; Fukai, Tomoki; Tsujino, Hiroshi

    2011-11-01

    Real-time simulation of a biologically realistic spiking neural network is necessary for evaluation of its capacity to interact with real environments. However, the real-time simulation of such a neural network is difficult due to its high computational costs that arise from two factors: (1) vast network size and (2) the complicated dynamics of biologically realistic neurons. In order to address these problems, mainly the latter, we chose to use general purpose computing on graphics processing units (GPGPUs) for simulation of such a neural network, taking advantage of the powerful computational capability of a graphics processing unit (GPU). As a target for real-time simulation, we used a model of the basal ganglia that has been developed according to electrophysiological and anatomical knowledge. The model consists of heterogeneous populations of 370 spiking model neurons, including computationally heavy conductance-based models, connected by 11,002 synapses. Simulation of the model has not yet been performed in real-time using a general computing server. By parallelization of the model on the NVIDIA Geforce GTX 280 GPU in data-parallel and task-parallel fashion, faster-than-real-time simulation was robustly realized with only one-third of the GPU's total computational resources. Furthermore, we used the GPU's full computational resources to perform faster-than-real-time simulation of three instances of the basal ganglia model; these instances consisted of 1100 neurons and 33,006 synapses and were synchronized at each calculation step. Finally, we developed software for simultaneous visualization of faster-than-real-time simulation output. These results suggest the potential power of GPGPU techniques in real-time simulation of realistic neural networks. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. The Advantages of Human Milk Recognize the Spatiotemporal Locations of Toxins and Intelligently Bypass Them by Forming a Hummingbird-Like Hovering Neural Network Circuitry Based on an Organic Biomimetic Choline Acetyltransferase Memristor/Memcapacitor Prosthesis

    National Research Council Canada - National Science Library

    E T Chen; J Thornton; P T Kissinger; S-H Duh

    2016-01-01

    ... by forming high frequency oscillation (HFO) in the brain circuitry when compared with organic cow milk samples based on an organic memristor/memcapacitor biomimetic Choline Acetyltransferase (CHAT...

  5. Neural circuits involved in the renewal of extinguished fear.

    Science.gov (United States)

    Chen, Weihai; Wang, Yan; Wang, Xiaqing; Li, Hong

    2017-07-01

    The last 10 years have witnessed a substantial progress in understanding the neural mechanisms for the renewal of the extinguished fear memory. Based on the theory of fear extinction, exposure therapy has been developed as a typical cognitive behavioral therapy for posttraumatic stress disorder. Although the fear memory can be extinguished by repeated presentation of conditioned stimulus without unconditioned stimulus, the fear memory is not erased and tends to relapse outside of extinction context, which is referred to as renewal. Therefore, the renewal is regarded as a great obstruction interfering with the effect of exposure therapy. In recent years, there has been a great deal of studies in understanding the neurobiological underpinnings of fear renewal. These offer a foundation upon which novel therapeutic interventions for the renewal may be built. This review focuses on behavioral, anatomical and electrophysiological studies that interpret roles of the hippocampus, prelimbic cortex and amygdala as well as the connections between them for the renewal of the extinguished fear. Additionally, this review suggests the possible pathways for the renewal: (1) the prelimbic cortex may integrate contextual information from hippocampal inputs and project to the basolateral amygdala to mediate the renewal of extinguished fear memory; the ventral hippocampus may innervate the activities of the basolateral amygdala or the central amygdala directly for the renewal. © 2017 IUBMB Life, 69(7):470-478, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  6. Neural mirroring and social interaction: Motor system involvement during action observation relates to early peer cooperation

    Directory of Open Access Journals (Sweden)

    H.M. Endedijk

    2017-04-01

    Full Text Available Whether we hand over objects to someone, play a team sport, or make music together, social interaction often involves interpersonal action coordination, both during instances of cooperation and entrainment. Neural mirroring is thought to play a crucial role in processing other’s actions and is therefore considered important for social interaction. Still, to date, it is unknown whether interindividual differences in neural mirroring play a role in interpersonal coordination during different instances of social interaction. A relation between neural mirroring and interpersonal coordination has particularly relevant implications for early childhood, since successful early interaction with peers is predictive of a more favorable social development. We examined the relation between neural mirroring and children’s interpersonal coordination during peer interaction using EEG and longitudinal behavioral data. Results showed that 4-year-old children with higher levels of motor system involvement during action observation (as indicated by lower beta-power were more successful in early peer cooperation. This is the first evidence for a relation between motor system involvement during action observation and interpersonal coordination during other instances of social interaction. The findings suggest that interindividual differences in neural mirroring are related to interpersonal coordination and thus successful social interaction.

  7. Neural mirroring and social interaction: Motor system involvement during action observation relates to early peer cooperation.

    Science.gov (United States)

    Endedijk, H M; Meyer, M; Bekkering, H; Cillessen, A H N; Hunnius, S

    2017-04-01

    Whether we hand over objects to someone, play a team sport, or make music together, social interaction often involves interpersonal action coordination, both during instances of cooperation and entrainment. Neural mirroring is thought to play a crucial role in processing other's actions and is therefore considered important for social interaction. Still, to date, it is unknown whether interindividual differences in neural mirroring play a role in interpersonal coordination during different instances of social interaction. A relation between neural mirroring and interpersonal coordination has particularly relevant implications for early childhood, since successful early interaction with peers is predictive of a more favorable social development. We examined the relation between neural mirroring and children's interpersonal coordination during peer interaction using EEG and longitudinal behavioral data. Results showed that 4-year-old children with higher levels of motor system involvement during action observation (as indicated by lower beta-power) were more successful in early peer cooperation. This is the first evidence for a relation between motor system involvement during action observation and interpersonal coordination during other instances of social interaction. The findings suggest that interindividual differences in neural mirroring are related to interpersonal coordination and thus successful social interaction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Control of energy balance by hypothalamic gene circuitry involving two nuclear receptors, neuron-derived orphan receptor 1 and glucocorticoid receptor.

    Science.gov (United States)

    Kim, Sun-Gyun; Lee, Bora; Kim, Dae-Hwan; Kim, Juhee; Lee, Seunghee; Lee, Soo-Kyung; Lee, Jae W

    2013-10-01

    Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-derived orphan receptor 1 (NOR1) and glucocorticoid receptor (GR), which directs the regulated expression of orexigenic neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in response to peripheral signals. Our results suggest that the anorexigenic signal leptin induces NOR1 expression likely via the transcription factor cyclic AMP response element-binding protein (CREB), while the orexigenic signal glucocorticoid mobilizes GR to inhibit NOR1 expression by antagonizing the action of CREB. Also, NOR1 suppresses glucocorticoid-dependent expression of AgRP and NPY. Consistently, relative to wild-type mice, NOR1-null mice showed significantly higher levels of AgRP and NPY and were less responsive to leptin in decreasing the expression of AgRP and NPY. These results identify mutual antagonism between NOR1 and GR to be a key rheostat for peripheral metabolic signals to centrally control energy balance.

  9. Functional characterization of obesogenic neural circuitries

    NARCIS (Netherlands)

    Boender, A.J.

    2015-01-01

    Obesity can be characterized as a disorder in which affected individuals fail to properly regulate the balance between energy intake and expenditure. Recently, genome-wide association studies have identified over 30 genetic variants that associate with increased body weight and thus provide clues on

  10. Neural mirroring and social interaction : Motor system involvement during action observation relates to early peer cooperation

    NARCIS (Netherlands)

    Endedijk, H. M.; Meyer, M.; Bekkering, H.; Cillessen, A. H. N.; Hunnius, Sabine

    2017-01-01

    Whether we hand over objects to someone, play a team sport, or make music together, social interaction often involves interpersonal action coordination, both during instances of cooperation and entrainment. Neural mirroring is thought to play a crucial role in processing other's actions and is

  11. Neural mirroring and social interaction: Motor system involvement during action observation relates to early peer cooperation

    NARCIS (Netherlands)

    Endedijk, H.M.; Meyer, M.; Bekkering, H.; Cillessen, A.H.N.; Hunnius, S.

    2017-01-01

    Whether we hand over objects to someone, play a team sport, or make music together, social interaction often involves interpersonal action coordination, both during instances of cooperation and entrainment. Neural mirroring is thought to play a crucial role in processing other's actions and is

  12. CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance.

    Science.gov (United States)

    Schulz, Yvonne; Wehner, Peter; Opitz, Lennart; Salinas-Riester, Gabriela; Bongers, Ernie M H F; van Ravenswaaij-Arts, Conny M A; Wincent, Josephine; Schoumans, Jacqueline; Kohlhase, Jürgen; Borchers, Annette; Pauli, Silke

    2014-08-01

    Heterozygous loss of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, cranial nerves and several organ systems. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far, only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition are unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7 (Whi/+) and Chd7 (Whi/Whi)) mouse embryos at day 9.5, a time point of neural crest cell migration. We identified 98 differentially expressed genes between wild-type and Chd7 (Whi/Whi) embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance such as semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 in Xenopus laevis embryos, we found abnormalities in the expression pattern of Sema3a, a protein involved in the pathogenesis of Kallmann syndrome, in vivo. In addition, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7-negative CHARGE patients. In summary, we discovered for the first time that Chd7 regulates genes involved in neural crest cell guidance, demonstrating a new aspect in the pathogenesis of CHARGE syndrome. Furthermore, we showed for Sema3a a conserved regulatory mechanism across different species, highlighting its significance during development. Although we postulated that the non-synonymous SEMA3A variants which we found in CHD7-negative CHARGE patients alone are not sufficient to produce the phenotype, we suggest an important modifier role for SEMA3A in the

  13. Optogenetic dissection of medial prefrontal cortex circuitry

    Directory of Open Access Journals (Sweden)

    Danai eRiga

    2014-12-01

    Full Text Available The medial prefrontal cortex (mPFC is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g. thalamus, striatum, amygdala and hippocampus, the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

  14. Neural substrates involved in anger induced by audio-visual film clips among patients with alcohol dependency.

    Science.gov (United States)

    Park, Mi-Sook; Lee, Bae Hwan; Sohn, Jin-Hun

    2016-07-08

    Very little is known about the neural circuitry underlying anger processing among alcoholics. The purpose of this study was to examine the altered brain activity of alcoholic individuals during transient anger emotion. Using functional magnetic resonance imaging (fMRI), 18 male patients diagnosed with alcohol dependence in an inpatient alcohol treatment facility and 16 social drinkers with similar demographics were scanned during the viewing of anger-provoking film clips. While there was no significant difference in the level of experienced anger between alcohol-dependent patients and non-alcoholic controls, significantly greater activation was observed in the bilateral dorsal anterior cingulate cortex (dACC) and the right precentral gyrus among alcoholic patients compared to the normal controls. In summary, specific brain regions were identified that are associated with anger among patients with alcohol dependency.

  15. Limbic circuitry activation in ethanol withdrawal is regulated by a chromosome 1 locus.

    Science.gov (United States)

    Buck, Kari J; Chen, Gang; Kozell, Laura B

    2017-02-01

    Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force sustaining alcohol use/abuse and contributing to relapse in alcoholics. Although no animal model exactly duplicates alcoholism, models for specific factors, including the withdrawal syndrome, are useful for identifying potential genetic and neural determinants of liability in humans. We previously identified highly significant quantitative trait loci (QTLs) with large effects on predisposition to withdrawal after chronic and acute alcohol exposure in mice and mapped these loci to the same region of chromosome 1 (Alcdp1 and Alcw1, respectively). The present studies utilize a novel Alcdp1/Alcw1 congenic model (in which an interval spanning Alcdp1 and Alcw1 from the C57BL/6J donor strain [build GRCm38 150.3-174.6 Mb] has been introgressed onto a uniform inbred DBA/2J genetic background) known to demonstrate significantly less severe chronic and acute withdrawal compared to appropriate background strain animals. Here, using c-Fos induction as a high-resolution marker of neuronal activation, we report that male Alcdp1/Alcw1 congenic animals demonstrate significantly less alcohol withdrawal-associated neural activation compared to appropriate background strain animals in the prelimbic and cingulate cortices of the prefrontal cortex as well as discrete regions of the extended amygdala (i.e., basolateral) and extended basal ganglia (i.e., dorsolateral striatum, and caudal substantia nigra pars reticulata). These studies are the first to begin to elucidate circuitry by which this confirmed addiction-relevant QTL could influence behavior. This circuitry overlaps limbic circuitry involved in stress, providing additional mechanistic information. Alcdp1/Alcw1 maps to a region syntenic with human chromosome 1q, where multiple studies find significant associations with risk for alcoholism. Published by Elsevier Inc.

  16. Neural Mechanisms Involved in Hypersensitive Hearing: Helping Children with ASD Who Are Overly Sensitive to Sounds.

    Science.gov (United States)

    Lucker, Jay R; Doman, Alex

    2015-01-01

    Professionals working with children diagnosed with autism spectrum disorder (ASD) may find that these children are overly sensitive to sounds. These professionals are often concerned as to why children may have auditory hypersensitivities. This review article discusses the neural mechanisms identified underlying hypersensitive hearing in people. The authors focus on brain research to support the idea of the nonclassical auditory pathways being involved in connecting the auditory system with the emotional system of the brain. The authors also discuss brain mechanisms felt to be involved in auditory hypersensitivity. The authors conclude with a discussion of some treatments for hypersensitive hearing. These treatments include desensitization training and the use of listening therapies such as The Listening Program.

  17. Neural Mechanisms Involved in Hypersensitive Hearing: Helping Children with ASD Who Are Overly Sensitive to Sounds

    Directory of Open Access Journals (Sweden)

    Jay R. Lucker

    2015-01-01

    Full Text Available Professionals working with children diagnosed with autism spectrum disorder (ASD may find that these children are overly sensitive to sounds. These professionals are often concerned as to why children may have auditory hypersensitivities. This review article discusses the neural mechanisms identified underlying hypersensitive hearing in people. The authors focus on brain research to support the idea of the nonclassical auditory pathways being involved in connecting the auditory system with the emotional system of the brain. The authors also discuss brain mechanisms felt to be involved in auditory hypersensitivity. The authors conclude with a discussion of some treatments for hypersensitive hearing. These treatments include desensitization training and the use of listening therapies such as The Listening Program.

  18. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    Vugler, Anthony A

    2010-01-01

    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  19. Understanding the neural mechanisms involved in sensory control of voice production.

    Science.gov (United States)

    Parkinson, Amy L; Flagmeier, Sabina G; Manes, Jordan L; Larson, Charles R; Rogers, Bill; Robin, Donald A

    2012-05-15

    Auditory feedback is important for the control of voice fundamental frequency (F0). In the present study we used neuroimaging to identify regions of the brain responsible for sensory control of the voice. We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. To determine the neural substrates involved in these audio-vocal responses, subjects underwent fMRI scanning while vocalizing with or without pitch-shifted feedback. The comparison of shifted and unshifted vocalization revealed activation bilaterally in the superior temporal gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the STG activity is related to error detection by auditory error cells located in the superior temporal cortex and efference copy mechanisms whereby this region is responsible for the coding of a mismatch between actual and predicted voice F0. Published by Elsevier Inc.

  20. Early Forming a Hummingbird-like Hovering Neural Network Circuitry Pattern with Reentrant Spatiotemporal Energy-Sensory Orientation Privileged to Avoid “Epilepsy” Based on a Biomimetic Acetylcholinesterase Memcapacitor Prosthesis

    Directory of Open Access Journals (Sweden)

    Ellen T. Chen

    2015-08-01

    Full Text Available The hummingbird’s significant asymmetry hovering flight with energy conservation pattern is remarkable among all vertebrates. However, little is known to human’s neuronal network circuitry current flow pattern for whether or not has this privilege during slow wave sleeping (SWS. What is the advantage in order to avoid diseases if we have this network pattern ? A memory device was developed with nanostructured biomimetic acetylcholinesterase (ACHE gorge membrane on gold chips as memcapacitor 1, served as a normal brain network prosthesis, compared with a mutated ACHE prosthesis as device 2, for evaluation of neuronal network circuitry integrity in the presence of Amyloid- beta (Ab under the conditions of free from tracers and antibodies in spiked NIST SRM 965A human serum. Three categories of Reentrant Energy-Sensory images are presented based on infused brain pulse energies in a matrix of “Sensory Biomarkers” having frequencies over 0.25-333 Hz at free and fixed Ab levels, respectively. Early non-symptomatic epilepsy was indentified and predicted by device 2 due to Pathological High Frequency Oscillation (pHFO and large areas of 38 µM Ab re-depositions. Device 1 sensitively “feels” Ab damage because of its Frequency Oscillation (HFO enhanced the hummingbird- like hovering pattern with higher reentrant energy sensitivity of 0.12 pj/bit/s/µm3 without Ab compared with Ab, 13 aj/bit/s/µm3/nM over 3.8-471 nM range over 0.003-4s. Device 1 reliably detected early CR dysfunction privileged to avoid epilepsy.

  1. PER2 rs2304672 polymorphism moderates circadian-relevant reward circuitry activity in adolescents.

    Science.gov (United States)

    Forbes, Erika E; Dahl, Ronald E; Almeida, Jorge R C; Ferrell, Robert E; Nimgaonkar, Vishwajit L; Mansour, Hader; Sciarrillo, Samantha R; Holm, Stephanie M; Rodriguez, Eric E; Phillips, Mary L

    2012-03-01

    Reward behavior in animals is influenced by circadian genes, including clock-pathway genes such as Period2 (PER2). Several forms of psychiatric illness are associated with both altered reward function and disturbances in circadian function. The PER2 single nucleotide polymorphism (SNP) rs2304672 has been associated with psychiatric illnesses involving reward dysfunction. Associations among circadian genes, function in neural reward circuits, and circadian-influenced behavior have not yet been studied in humans, however. 90 healthy adolescents underwent functional magnetic resonance imaging during a guessing task with monetary reward, genotyping for two PER2 SNPs (rs2304672, rs2304674), and actigraphy to measure sleep in their home environments. Weekend sleep midpoint, a behavioral index of circadian function, was derived from actigraphy. Puberty was measured by physical exam. The rs2304672 SNP predicted blood oxygenation level-dependent response to monetary reward as constrained by sleep midpoint. Later sleep midpoint was associated with reduced activity in a key component of reward circuitry, medial prefrontal cortex (mPFC; Brodmann area 9/10/32), to reward outcome (p(corrected) circadian genes have a significant impact upon circadian-relevant reward circuitry in humans. These findings have the potential to elucidate gene-brain-behavior relationships underlying reward processing and psychopathology.

  2. Neural Correlates of Successful and Unsuccessful Strategical Mechanisms Involved in Uncertain Decision-Making.

    Directory of Open Access Journals (Sweden)

    Julie Giustiniani

    Full Text Available The ability to develop successful long-term strategies in uncertain situations relies on complex neural mechanisms. Although lesion studies have shown some of the mechanisms involved, it is still unknown why some healthy subjects are able to make the right decision whereas others are not. The aim of our study was to investigate neurophysiological differences underlying this ability to develop a successful strategy in a group of healthy subjects playing a monetary card game called the Iowa Gambling Task (IGT. In this task, subjects have to win and earn money by choosing between four decks of cards, two were advantageous in the long term and two disadvantageous. Twenty healthy right-handed subjects performed the IGT while their cerebral activity was recorded by electroencephalography. Based on their behavioral performances, two groups of subjects could clearly be distinguished: one who selected the good decks and thus succeeded in developing a Favorable strategy (9 subjects and one who remained Undecided (11 subjects. No neural difference was found between each group before the selection of a deck, but in both groups a greater negativity was found emerging from the right superior frontal gyrus 600 ms before a disadvantageous selection. During the processing of the feedback, an attenuation of the P200 and P300 waveforms was found for the Undecided group, and a P300 originating from the medial frontal gyrus was found in response to a loss only in the Favorable group. Our results suggest that undecided subjects are hyposensitive to the valence of the cards during gambling, which affects the feedback processing.

  3. Neural Correlates of Successful and Unsuccessful Strategical Mechanisms Involved in Uncertain Decision-Making.

    Science.gov (United States)

    Giustiniani, Julie; Gabriel, Damien; Nicolier, Magali; Monnin, Julie; Haffen, Emmanuel

    2015-01-01

    The ability to develop successful long-term strategies in uncertain situations relies on complex neural mechanisms. Although lesion studies have shown some of the mechanisms involved, it is still unknown why some healthy subjects are able to make the right decision whereas others are not. The aim of our study was to investigate neurophysiological differences underlying this ability to develop a successful strategy in a group of healthy subjects playing a monetary card game called the Iowa Gambling Task (IGT). In this task, subjects have to win and earn money by choosing between four decks of cards, two were advantageous in the long term and two disadvantageous. Twenty healthy right-handed subjects performed the IGT while their cerebral activity was recorded by electroencephalography. Based on their behavioral performances, two groups of subjects could clearly be distinguished: one who selected the good decks and thus succeeded in developing a Favorable strategy (9 subjects) and one who remained Undecided (11 subjects). No neural difference was found between each group before the selection of a deck, but in both groups a greater negativity was found emerging from the right superior frontal gyrus 600 ms before a disadvantageous selection. During the processing of the feedback, an attenuation of the P200 and P300 waveforms was found for the Undecided group, and a P300 originating from the medial frontal gyrus was found in response to a loss only in the Favorable group. Our results suggest that undecided subjects are hyposensitive to the valence of the cards during gambling, which affects the feedback processing.

  4. Successful dieters have increased neural activity in cortical areas involved in the control of behavior.

    Science.gov (United States)

    DelParigi, A; Chen, K; Salbe, A D; Hill, J O; Wing, R R; Reiman, E M; Tataranni, P A

    2007-03-01

    To investigate whether dietary restraint, a landmark of successful dieting, is associated with specific patterns of brain responses to the sensory experience of food and meal consumption. Cross-sectional study of the brain's response to the sensory experience of food and meal consumption in nine successful dieters (age: 38+/-7 years, body fat (%): 28+/-3) and 20 non-dieters (age: 31+/-9 years, body fat (%): 33+/-9), all women. Changes in brain activity in response to the sensory experience of food and meal consumption were assessed by using positron emission tomography and (15)O water as a radiotracer. Body fatness was assessed by dual X-ray absorptiometry. Subjective ratings of hunger and fullness were measured by visual analogue scale. Dietary restraint, disinhibition and hunger were assessed by the Three Factor Eating Questionnaire. Successful dieters had a significantly higher level of dietary restraint compared to non-dieters. In response to meal consumption, successful dieters had a greater activation in the dorsal prefrontal cortex (DPFC), dorsal striatum and anterior cerebellar lobe as compared to non-dieters. In response to the same stimulation, the orbitofrontal cortex (OFC) was significantly more activated in non-dieters as compared to successful dieters. Dietary restraint was positively correlated with the response in the DPFC and negatively with the response in the OFC. The responses in the DPFC and OFC were negatively intercorrelated. Cortical areas involved in controlling inappropriate behavioral responses, such as the DPFC, are particularly activated in successful dieters in response to meal consumption. The association between the degree of dietary restraint and the coordinated neural changes in the DPFC and OFC raises the possibility that cognitive control of food intake is achieved by modulating neural circuits controlling food reward.

  5. Memristor Circuitry via Material Implication

    Science.gov (United States)

    Wright, Anna; Gergel-Hackett, Nadine

    Memristors are novel nanoelectronic devices that have advantages over traditional computer circuitry (eg., they are nonvolatile, two-terminal, and low power) and thus have potential circuit applications for both digital logic and memory. In this work, we used a simple memristor model that was designed to replicate the real-world electrical characteristics of previously fabricated and tested memristor devices. This model was developed and constructed with basic circuit elements using a free and widely available circuit simulator, LT Spice. We updated this model to more realistically simulate memristor behavior and then theoretically demonstrated that the model can be used to build memristor-based material implication gates (IMPLY gates). The development of these IMPLY gates is a critical step in the realization of memristor-based digital logic because they can be combined to act in place of any of the basic traditional logic gates (AND, NAND, etc), and thus enable efficient entirely memristor-based computing.

  6. Thalamic Multisensory integration: Creating a neural network map of involved brain areas in music perception, processing and execution

    NARCIS (Netherlands)

    Jaschke, A.C.; Scherder, E.J.A.

    2013-01-01

    Music activates a wide array of neural areas involved in different functions besides the perception, processing and execution of music itself. Understanding musical processes in the brain has had multiple implications in the neuro- and health sciences. Engaging the brain with a multisensory stimulus

  7. Let7a involves in neural stem cell differentiation relating with TLX level

    Energy Technology Data Exchange (ETDEWEB)

    Song, Juhyun [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Kyoung Joo; Oh, Yumi [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Jong Eun, E-mail: jelee@yuhs.ac [Department of Anatomy, Yonsei University College of Medicine, Seoul (Korea, Republic of); BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-07-10

    Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. - Highlights: • Let7a influences on NSC differentiation and proliferation. • Let7a involves in mainly NSC differentiation rather than proliferation. • Let7a positively regulates the TLX expression.

  8. Nrf2/ARE Pathway Involved in Oxidative Stress Induced by Paraquat in Human Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tingting Dou

    2016-01-01

    Full Text Available Compelling evidences have shown that diverse environmental insults arising during early life can either directly lead to a reduction in the number of dopaminergic neurons or cause an increased susceptibility to neurons degeneration with subsequent environmental insults or with aging alone. Oxidative stress is considered the main effect of neurotoxins exposure. In this study, we investigated the oxidative stress effect of Paraquat (PQ on immortalized human embryonic neural progenitor cells by treating them with various concentrations of PQ. We show that PQ can decrease the activity of SOD and CAT but increase MDA and LDH level. Furthermore, the activities of Cyc and caspase-9 were found increased significantly at 10 μM of PQ treatment. The cytoplasmic Nrf2 protein expressions were upregulated at 10 μM but fell back at 100 μM. The nuclear Nrf2 protein expressions were upregulated as well as the downstream mRNA expressions of HO-1 and NQO1 in a dose-dependent manner. In addition, the proteins expression of PKC and CKII was also increased significantly even at 1 μM. The results suggested that Nrf2/ARE pathway is involved in mild to moderate PQ-induced oxidative stress which is evident from dampened Nrf2 activity and low expression of antioxidant genes in PQ induced oxidative damage.

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

    Science.gov (United States)

    Kim, Jusik; Choi, Inseo; Lee, Youngsoo

    2017-11-01

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

  10. Cognitive processes involved in smooth pursuit eye movements: behavioral evidence, neural substrate and clinical correlation

    Directory of Open Access Journals (Sweden)

    Kikuro eFukushima

    2013-03-01

    Full Text Available Smooth-pursuit eye movements allow primates to track moving objects. Efficient pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Prediction depends on expectation of future object motion, storage of motion information and use of extra-retinal mechanisms in addition to visual feedback. We present behavioural evidence of how cognitive processes are involved in predictive pursuit in normal humans and then describe neuronal responses in monkeys and behavioural responses in patients using a new technique to test these cognitive controls. The new technique examines the neural substrate of working memory and movement preparation for predictive pursuit by using a memory-based task in macaque monkeys trained to pursue (go or not pursue (no-go according to a go/no-go cue, in a direction based on memory of a previously presented visual motion display. Single-unit task-related neuronal activity was examined in medial superior temporal cortex (MST, supplementary eye fields (SEF, caudal frontal eye fields (FEF, cerebellar dorsal vermis lobules VI-VII, caudal fastigial nuclei (cFN, and floccular region. Neuronal activity reflecting working memory of visual motion direction and go/no-go selection was found predominantly in SEF, cerebellar dorsal vermis and cFN, whereas movement preparation related signals were found predominantly in caudal FEF and the same cerebellar areas. Chemical inactivation produced effects consistent with differences in signals represented in each area. When applied to patients with Parkinson's disease, the task revealed deficits in movement preparation but not working memory. In contrast, patients with frontal cortical or cerebellar dysfunction had high error rates, suggesting impaired working memory. We show how neuronal activity may be explained by models of retinal and extra-retinal interaction in target selection and predictive control and thus aid understanding of underlying

  11. Cognitive processes involved in smooth pursuit eye movements: behavioral evidence, neural substrate and clinical correlation.

    Science.gov (United States)

    Fukushima, Kikuro; Fukushima, Junko; Warabi, Tateo; Barnes, Graham R

    2013-01-01

    Smooth-pursuit eye movements allow primates to track moving objects. Efficient pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Prediction depends on expectation of future object motion, storage of motion information and use of extra-retinal mechanisms in addition to visual feedback. We present behavioral evidence of how cognitive processes are involved in predictive pursuit in normal humans and then describe neuronal responses in monkeys and behavioral responses in patients using a new technique to test these cognitive controls. The new technique examines the neural substrate of working memory and movement preparation for predictive pursuit by using a memory-based task in macaque monkeys trained to pursue (go) or not pursue (no-go) according to a go/no-go cue, in a direction based on memory of a previously presented visual motion display. Single-unit task-related neuronal activity was examined in medial superior temporal cortex (MST), supplementary eye fields (SEF), caudal frontal eye fields (FEF), cerebellar dorsal vermis lobules VI-VII, caudal fastigial nuclei (cFN), and floccular region. Neuronal activity reflecting working memory of visual motion direction and go/no-go selection was found predominantly in SEF, cerebellar dorsal vermis and cFN, whereas movement preparation related signals were found predominantly in caudal FEF and the same cerebellar areas. Chemical inactivation produced effects consistent with differences in signals represented in each area. When applied to patients with Parkinson's disease (PD), the task revealed deficits in movement preparation but not working memory. In contrast, patients with frontal cortical or cerebellar dysfunction had high error rates, suggesting impaired working memory. We show how neuronal activity may be explained by models of retinal and extra-retinal interaction in target selection and predictive control and thus aid understanding of underlying

  12. Cognitive processes involved in smooth pursuit eye movements: behavioral evidence, neural substrate and clinical correlation

    Science.gov (United States)

    Fukushima, Kikuro; Fukushima, Junko; Warabi, Tateo; Barnes, Graham R.

    2013-01-01

    Smooth-pursuit eye movements allow primates to track moving objects. Efficient pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Prediction depends on expectation of future object motion, storage of motion information and use of extra-retinal mechanisms in addition to visual feedback. We present behavioral evidence of how cognitive processes are involved in predictive pursuit in normal humans and then describe neuronal responses in monkeys and behavioral responses in patients using a new technique to test these cognitive controls. The new technique examines the neural substrate of working memory and movement preparation for predictive pursuit by using a memory-based task in macaque monkeys trained to pursue (go) or not pursue (no-go) according to a go/no-go cue, in a direction based on memory of a previously presented visual motion display. Single-unit task-related neuronal activity was examined in medial superior temporal cortex (MST), supplementary eye fields (SEF), caudal frontal eye fields (FEF), cerebellar dorsal vermis lobules VI–VII, caudal fastigial nuclei (cFN), and floccular region. Neuronal activity reflecting working memory of visual motion direction and go/no-go selection was found predominantly in SEF, cerebellar dorsal vermis and cFN, whereas movement preparation related signals were found predominantly in caudal FEF and the same cerebellar areas. Chemical inactivation produced effects consistent with differences in signals represented in each area. When applied to patients with Parkinson's disease (PD), the task revealed deficits in movement preparation but not working memory. In contrast, patients with frontal cortical or cerebellar dysfunction had high error rates, suggesting impaired working memory. We show how neuronal activity may be explained by models of retinal and extra-retinal interaction in target selection and predictive control and thus aid understanding of underlying

  13. Robust Langmuir probe circuitry for fusion research

    Science.gov (United States)

    Boedo, J.; Gunner, G.; Gray, D.; Conn, R.

    2001-02-01

    Langmuir probes attached to the plasma facing components of fusion experiments are biased with constant or swept voltages to obtain measurements of plasma parameters such as electron temperature and density. The circuitry used must be rugged and protect the power supplies and electronics against generally harsh conditions and sudden discharge terminations, or disruptions. Modularity, ease of repair and expandability are important because short-lived radiation from neutron activation is often present after the discharges, preventing access to the circuitry. We report the implementation of modular probe circuitry featuring robust protection, remote testing and reset and easy maintenance and expandability, achieved by using DIN-rail modules.

  14. Involvement of Neptune in induction of the hatching gland and neural crest in the Xenopus embryo.

    Science.gov (United States)

    Kurauchi, Takayuki; Izutsu, Yumi; Maéno, Mitsugu

    2010-01-01

    Neptune, a Krüppel-like transcription factor, is expressed in various regions of the developing Xenopus embryo and it has multiple functions in the process of development in various organs. In situ hybridization analysis showed that Neptune is expressed in the boundary region between neural and non-neural tissues at the neurula stage, but little is known about the function of Neptune in this region. Here, we examined the expression and function of Neptune in the neural plate border (NPB) in the Xenopus embryo. Depletion of Neptune protein in developing embryos by using antisense MO caused loss of the hatching gland and otic vesicle as well as malformation of neural crest-derived cranial cartilages and melanocytes. Neptune MO also suppressed the expression of hatching gland and neural crest markers such as he, snail2, sox9 and msx1 at the neurula stage. Subsequent experiments showed that Neptune is necessary and sufficient for the differentiation of hatching gland cells and that it is located downstream of pax3 in the signal regulating the differentiation of these cells. Thus, Neptune is a new member of hatching gland specifier and plays a physiological role in determination and specification of multiple lineages derived from the NPB region.

  15. Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments

    Directory of Open Access Journals (Sweden)

    Meng-Qi Zhang

    2017-01-01

    Full Text Available Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient’s quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sleep, therapeutic sleep deprivation, and depression. This correlation might help us to understand better the mechanism underlying development of depression and the role of sleep. In this review, we first introduce the structure of sleep and the facilitated neural plasticity caused by physiological sleep. Then, we introduce sleep disturbances and changes in plasticity in patients with depression. Finally, the effects and mechanisms of antidepressants and therapeutic sleep deprivation on neural plasticity are discussed.

  16. Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments.

    Science.gov (United States)

    Zhang, Meng-Qi; Li, Rui; Wang, Yi-Qun; Huang, Zhi-Li

    2017-01-01

    Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient's quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sleep, therapeutic sleep deprivation, and depression. This correlation might help us to understand better the mechanism underlying development of depression and the role of sleep. In this review, we first introduce the structure of sleep and the facilitated neural plasticity caused by physiological sleep. Then, we introduce sleep disturbances and changes in plasticity in patients with depression. Finally, the effects and mechanisms of antidepressants and therapeutic sleep deprivation on neural plasticity are discussed.

  17. Involvement of crosstalk between Oct4 and Meis1a in neural cell fate decision.

    Directory of Open Access Journals (Sweden)

    Takeyuki Yamada

    Full Text Available Oct4 plays a critical role both in maintaining pluripotency and the cell fate decision of embryonic stem (ES cells. Nonetheless, in the determination of the neuroectoderm (NE from ES cells, the detailed regulation mechanism of the Oct4 gene expression is poorly understood. Here, we report that crosstalk between Oct4 and Meis1a, a Pbx-related homeobox protein, is required for neural differentiation of mouse P19 embryonic carcinoma (EC cells induced by retinoic acid (RA. During neural differentiation, Oct4 expression was transiently enhanced during 6-12 h of RA addition and subsequently disappeared within 48 h. Coinciding with up-regulation of Oct4 expression, the induction of Meis1a expression was initiated and reached a plateau at 48 h, suggesting that transiently induced Oct4 activates Meis1a expression and the up-regulated Meis1a then suppresses Oct4 expression. Chromatin immunoprecipitation (ChIP and luciferase reporter analysis showed that Oct4 enhanced Meis1a expression via direct binding to the Meis1 promoter accompanying histone H3 acetylation and appearance of 5-hydoxymethylcytosine (5hmC, while Meis1a suppressed Oct4 expression via direct association with the Oct4 promoter together with histone deacetylase 1 (HDAC1. Furthermore, ectopic Meis1a expression promoted neural differentiation via formation of large neurospheres that expressed Nestin, GLAST, BLBP and Sox1 as neural stem cell (NSC/neural progenitor markers, whereas its down-regulation generated small neurospheres and repressed neural differentiation. Thus, these results imply that crosstalk between Oct4 and Meis1a on mutual gene expressions is essential for the determination of NE from EC cells.

  18. Differences in brain circuitry for appetitive and reactive aggression as revealed by realistic auditory scripts

    Directory of Open Access Journals (Sweden)

    James Kenneth Moran

    2014-12-01

    Full Text Available Aggressive behavior is thought to divide into two motivational elements: The first being a self-defensively motivated aggression against threat and a second, hedonically motivated ‘appetitive’ aggression. Appetitive aggression is the less understood of the two, often only researched within abnormal psychology. Our approach is to understand it as a universal and adaptive response, and examine the functional neural activity of ordinary men (N=50 presented with an imaginative listening task involving a murderer describing a kill. We manipulated motivational context in a between-subjects design to evoke appetitive or reactive aggression, against a neutral control, measuring activity with Magnetoencephalography (MEG. Results show differences in left frontal regions in delta (2-5 Hz and alpha band (8-12 Hz for aggressive conditions and right parietal delta activity differentiating appetitive and reactive aggression. These results validate the distinction of reward-driven appetitive aggression from reactive aggression in ordinary populations at the level of functional neural brain circuitry.

  19. Brain imaging reveals neuronal circuitry underlying the crow’s perception of human faces

    Science.gov (United States)

    Marzluff, John M.; Miyaoka, Robert; Minoshima, Satoshi; Cross, Donna J.

    2012-01-01

    Crows pay close attention to people and can remember specific faces for several years after a single encounter. In mammals, including humans, faces are evaluated by an integrated neural system involving the sensory cortex, limbic system, and striatum. Here we test the hypothesis that birds use a similar system by providing an imaging analysis of an awake, wild animal’s brain as it performs an adaptive, complex cognitive task. We show that in vivo imaging of crow brain activity during exposure to familiar human faces previously associated with either capture (threatening) or caretaking (caring) activated several brain regions that allow birds to discriminate, associate, and remember visual stimuli, including the rostral hyperpallium, nidopallium, mesopallium, and lateral striatum. Perception of threatening faces activated circuitry including amygdalar, thalamic, and brainstem regions, known in humans and other vertebrates to be related to emotion, motivation, and conditioned fear learning. In contrast, perception of caring faces activated motivation and striatal regions. In our experiments and in nature, when perceiving a threatening face, crows froze and fixed their gaze (decreased blink rate), which was associated with activation of brain regions known in birds to regulate perception, attention, fear, and escape behavior. These findings indicate that, similar to humans, crows use sophisticated visual sensory systems to recognize faces and modulate behavioral responses by integrating visual information with expectation and emotion. Our approach has wide applicability and potential to improve our understanding of the neural basis for animal behavior. PMID:22984177

  20. STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats.

    Science.gov (United States)

    Tang, Qing-Ping; Shen, Qin; Wu, Li-Xiang; Feng, Xiang-Ling; Liu, Hui; Wu, Bei; Huang, Xiao-Song; Wang, Gai-Qing; Li, Zhong-Hao; Liu, Zun-Jing

    2016-07-01

    Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes.

  1. Social discounting involves modulation of neural value signals by temporoparietal junction

    Science.gov (United States)

    Strombach, Tina; Weber, Bernd; Hangebrauk, Zsofia; Kenning, Peter; Karipidis, Iliana I.; Tobler, Philippe N.; Kalenscher, Tobias

    2015-01-01

    Most people are generous, but not toward everyone alike: generosity usually declines with social distance between individuals, a phenomenon called social discounting. Despite the pervasiveness of social discounting, social distance between actors has been surprisingly neglected in economic theory and neuroscientific research. We used functional magnetic resonance imaging (fMRI) to study the neural basis of this process to understand the neural underpinnings of social decision making. Participants chose between selfish and generous alternatives, yielding either a large reward for the participant alone, or smaller rewards for the participant and another individual at a particular social distance. We found that generous choices engaged the temporoparietal junction (TPJ). In particular, the TPJ activity was scaled to the social-distance–dependent conflict between selfish and generous motives during prosocial choice, consistent with ideas that the TPJ promotes generosity by facilitating overcoming egoism bias. Based on functional coupling data, we propose and provide evidence for a biologically plausible neural model according to which the TPJ supports social discounting by modulating basic neural value signals in the ventromedial prefrontal cortex to incorporate social-distance–dependent other-regarding preferences into an otherwise exclusively own-reward value representation. PMID:25605887

  2. Differentiation of Neural Stem Cells into Oligodendrocytes : Involvement of the Polycomb Group Protein Ezh2

    NARCIS (Netherlands)

    Sher, Falak; Rossler, Reinhard; Brouwer, Nieske; Balasubramaniyan, Veerakumar; Boddeke, Erik; Copray, Sjef

    2008-01-01

    The mechanisms underlying the regulation of neural stem cell (NSC) renewal and maintenance of their multipotency are still not completely understood. Self-renewal of stem cells in general implies repression of genes that encode for cell lineage differentiation. Enhancer of zeste homolog 2 (Ezh2) is

  3. Jarid1b targets genes regulating development and is involved in neural differentiation

    DEFF Research Database (Denmark)

    Schmitz, Sandra U; Albert, Mareike; Malatesta, Martina

    2011-01-01

    -renewal and differentiation is just starting to emerge. Here, we show that the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for ESC self-renewal, but essential for ESC differentiation along the neural lineage. By genome-wide location analysis, we demonstrate that Jarid1b localizes predominantly...

  4. Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments

    OpenAIRE

    Meng-Qi Zhang; Rui Li; Yi-Qun Wang; Zhi-Li Huang

    2017-01-01

    Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient’s quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sl...

  5. Interdisciplinary approaches of transcranial magnetic stimulation applied to a respiratory neuronal circuitry model.

    Directory of Open Access Journals (Sweden)

    Stéphane Vinit

    Full Text Available Respiratory related diseases associated with the neuronal control of breathing represent life-threatening issues and to date, no effective therapeutics are available to enhance the impaired function. The aim of this study was to determine whether a preclinical respiratory model could be used for further studies to develop a non-invasive therapeutic tool applied to rat diaphragmatic neuronal circuitry. Transcranial magnetic stimulation (TMS was performed on adult male Sprague-Dawley rats using a human figure-of-eight coil. The largest diaphragmatic motor evoked potentials (MEPdia were recorded when the center of the coil was positioned 6 mm caudal from Bregma, involving a stimulation of respiratory supraspinal pathways. Magnetic shielding of the coil with mu metal reduced magnetic field intensities and improved focality with increased motor threshold and lower amplitude recruitment curve. Moreover, transynaptic neuroanatomical tracing with pseudorabies virus (applied to the diaphragm suggest that connections exist between the motor cortex, the periaqueductal grey cell regions, several brainstem neurons and spinal phrenic motoneurons (distributed in the C3-4 spinal cord. These results reveal the anatomical substrate through which supraspinal stimulation can convey descending action potential volleys to the spinal motoneurons (directly or indirectly. We conclude that MEPdia following a single pulse of TMS can be successfully recorded in the rat and may be used in the assessment of respiratory supraspinal plasticity. Supraspinal non-invasive stimulations aimed to neuromodulate respiratory circuitry will enable new avenues of research into neuroplasticity and the development of therapies for respiratory dysfunction associated with neural injury and disease (e.g. spinal cord injury, amyotrophic lateral sclerosis.

  6. Neuroanatomical circuitry associated with exploratory eye movement in schizophrenia: a voxel-based morphometric study.

    Directory of Open Access Journals (Sweden)

    Linlin Qiu

    Full Text Available Schizophrenic patients present abnormalities in a variety of eye movement tasks. Exploratory eye movement (EEM dysfunction appears to be particularly specific to schizophrenia. However, the underlying mechanisms of EEM dysfunction in schizophrenia are not clearly understood. To assess the potential neuroanatomical substrates of EEM, we recorded EEM performance and conducted a voxel-based morphometric analysis of gray matter in 33 schizophrenic patients and 29 well matched healthy controls. In schizophrenic patients, decreased responsive search score (RSS and widespread gray matter density (GMD reductions were observed. Moreover, the RSS was positively correlated with GMD in distributed brain regions in schizophrenic patients. Furthermore, in schizophrenic patients, some brain regions with neuroanatomical deficits overlapped with some ones associated with RSS. These brain regions constituted an occipito-tempro-frontal circuitry involved in visual information processing and eye movement control, including the left calcarine cortex [Brodmann area (BA 17], the left cuneus (BA 18, the left superior occipital cortex (BA 18/19, the left superior frontal gyrus (BA 6, the left cerebellum, the right lingual cortex (BA 17/18, the right middle occipital cortex (BA19, the right inferior temporal cortex (BA 37, the right dorsolateral prefrontal cortex (BA 46 and bilateral precentral gyri (BA 6 extending to the frontal eye fields (FEF, BA 8. To our knowledge, we firstly reported empirical evidence that gray matter loss in the occipito-tempro-frontal neuroanatomical circuitry of visual processing system was associated with EEM performance in schizophrenia, which may be helpful for the future effort to reveal the underlying neural mechanisms for EEM disturbances in schizophrenia.

  7. Neural fuzzy digital filtering: multivariate identifier filters involving multiple inputs and multiple outputs (MIMO

    Directory of Open Access Journals (Sweden)

    Juan Carlos García Infante

    2011-01-01

    Full Text Available  Multivariate identifier filters (multiple inputs and multiple outputs - MIMO are adaptive digital systems having a loop in accordance with an objective function to adjust matrix parameter convergence to observable reference system dynamics. One way of complying with this condition is to use fuzzy logic inference mechanisms which interpret and select the best matrix parameter from a knowledge base. Such selection mechanisms with neural networks can provide a response from the best operational level for each change in state (Shannon, 1948. This paper considers the MIMO digital filter model using neuro fuzzy digital filtering to find an adaptive  parameter matrix which is integrated into the Kalman filter by the transition matrix. The filter uses the neural network as back-propagation into the fuzzy mechanism to do this, interpreting its variables and its respective levels and selecting the best values for automatically adjusting transition matrix values. The Matlab simulation describes the neural fuzzy digital filter giving an approximation of exponential convergence seen in functional error. 

  8. Signal conditioning circuitry design for instrumentation systems.

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Cory A.

    2012-01-01

    This report details the current progress in the design, implementation, and validation of the signal conditioning circuitry used in a measurement instrumentation system. The purpose of this text is to document the current progress of a particular design in signal conditioning circuitry in an instrumentation system. The input of the signal conditioning circuitry comes from a piezoresistive transducer and the output will be fed to a 250 ksps, 12-bit analog-to-digital converter (ADC) with an input range of 0-5 V. It is assumed that the maximum differential voltage amplitude input from the sensor is 20 mV with an unknown, but presumably high, sensor bandwidth. This text focuses on a specific design; however, the theory is presented in such a way that this text can be used as a basis for future designs.

  9. Physiological evidence of neural pathways involved in reflexogenic penile erection in the rat.

    Science.gov (United States)

    Rampin, O; Giuliano, F; Dompeyre, P; Rousseau, J P

    1994-10-24

    To elucidate neural pathways responsible for the occurrence of reflexogenic erections, the response of the corpus cavernosum to electrical stimulation of the dorsal nerve of the penis (DNP) was measured in anesthetized, acutely spinalized rats. Stimulation elicited a dramatic increase in intracavernous pressure (ICP). ICP response was decreased by 70% after sectioning the pelvic nerve homolaterally to the stimulated DNP and abolished after bilateral section. ICP response was not impaired by curarization, but its latency was lengthened. Thus we physiologically evidenced a reflex loop independent from supraspinal centers between DNP and the pelvic nerve supporting penile reflexogenic erection.

  10. Tricyclic antidepressant amitriptyline indirectly increases the proliferation of adult dentate gyrus-derived neural precursors: an involvement of astrocytes.

    Directory of Open Access Journals (Sweden)

    Shuken Boku

    Full Text Available Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG, which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP, we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI, a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA. These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes.

  11. Construction of functional neuronal circuitry in the olfactory bulb.

    Science.gov (United States)

    Imai, Takeshi

    2014-11-01

    Recent studies using molecular genetics, electrophysiology, in vivo imaging, and behavioral analyses have elucidated detailed connectivity and function of the mammalian olfactory circuits. The olfactory bulb is the first relay station of olfactory perception in the brain, but it is more than a simple relay: olfactory information is dynamically tuned by local olfactory bulb circuits and converted to spatiotemporal neural code for higher-order information processing. Because the olfactory bulb processes ∼1000 discrete input channels from different odorant receptors, it serves as a good model to study neuronal wiring specificity, from both functional and developmental aspects. This review summarizes our current understanding of the olfactory bulb circuitry from functional standpoint and discusses important future studies with particular focus on its development and plasticity. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems.

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    Jarred Younger

    2010-10-01

    Full Text Available The early stages of a new romantic relationship are characterized by intense feelings of euphoria, well-being, and preoccupation with the romantic partner. Neuroimaging research has linked those feelings to activation of reward systems in the human brain. The results of those studies may be relevant to pain management in humans, as basic animal research has shown that pharmacologic activation of reward systems can substantially reduce pain. Indeed, viewing pictures of a romantic partner was recently demonstrated to reduce experimental thermal pain. We hypothesized that pain relief evoked by viewing pictures of a romantic partner would be associated with neural activations in reward-processing centers. In this functional magnetic resonance imaging (fMRI study, we examined fifteen individuals in the first nine months of a new, romantic relationship. Participants completed three tasks under periods of moderate and high thermal pain: 1 viewing pictures of their romantic partner, 2 viewing pictures of an equally attractive and familiar acquaintance, and 3 a word-association distraction task previously demonstrated to reduce pain. The partner and distraction tasks both significantly reduced self-reported pain, although only the partner task was associated with activation of reward systems. Greater analgesia while viewing pictures of a romantic partner was associated with increased activity in several reward-processing regions, including the caudate head, nucleus accumbens, lateral orbitofrontal cortex, amygdala, and dorsolateral prefrontal cortex--regions not associated with distraction-induced analgesia. The results suggest that the activation of neural reward systems via non-pharmacologic means can reduce the experience of pain.

  13. Feedback circuitry via let-7c between lncRNA CCAT1 and c-Myc is involved in cigarette smoke extract-induced malignant transformation of HBE cells.

    Science.gov (United States)

    Lu, Lu; Qi, Hong; Luo, Fei; Xu, Hui; Ling, Min; Qin, Yu; Yang, Ping; Liu, Xinlu; Yang, Qianlei; Xue, Junchao; Chen, Chao; Lu, Jiachun; Xiang, Quanyong; Liu, Qizhan; Bian, Qian

    2017-03-21

    Cigarette smoking is a primary risk factor for the development of lung cancer, which is regarded as the leading cause of cancer-related deaths. The process of malignant transformation of cells, however, is complex and elusive. The present study investigated the roles of an lncRNA, CCAT1, and a transcriptional factor, c-Myc, in human bronchial epithelial (HBE) cell transformation induced by cigarette smoke extract. With acute and chronic treatment of HBE cells, cigarette smoke extract induced increases of CCAT1 and c-Myc levels and decreases of levels of let-7c, a microRNA. Down-regulation of c-Myc reduced the degree of malignancy and the invasion/migration capacity of HBE cells transformed by cigarette smoke extract. ChIP assays established that c-Myc, increased by cigarette smoke extract, binds to the promoter of CCAT1, activating its transcription. Further, let-7c suppressed the expression of c-Myc through binding to its 3'-UTR. In turn, CCAT1 promoted the accumulation of c-Myc through binding to let-7c and decreasing free let-7c, which influenced the neoplastic capacity of HBE cells transformed by cigarette smoke extract. These results indicate that a positive feedback loop ensures expression of cigarette smoke extract-induced CCAT1 and c-Myc via let-7c, which is involved in cigarette smoke extract-induced malignant transformation of HBE cells. Thus, the present research establishes a new mechanism for the reciprocal regulation between CCAT1 and c-Myc and provides an understanding of cigarette smoke extract-induced lung carcinogenesis.

  14. The influence of group membership on the neural correlates involved in empathy

    National Research Council Canada - National Science Library

    Eres, Robert; Molenberghs, Pascal

    2013-01-01

    Empathy involves affective, cognitive, and emotion regulative components. The affective component relies on the sharing of emotional states with others and is discussed here in relation to the human Mirror System...

  15. Neural mechanisms underlying stop-and-restart difficulties: involvement of the motor and perceptual systems.

    Directory of Open Access Journals (Sweden)

    Kentaro Yamanaka

    Full Text Available The ability to suddenly stop a planned movement or a movement being performed and restart it after a short interval is an important mechanism that allows appropriate behavior in response to contextual or environmental changes. However, performing such stop-and-restart movements smoothly is difficult at times. We investigated performance (response time of stop-and-restart movements using a go/stop/re-go task and found consistent stop-and-restart difficulties after short (~100 ms stop-to-restart intervals (SRSI, and an increased probability of difficulties after longer (>200 ms SRSIs, suggesting that two different mechanisms underlie stop-and-restart difficulties. Next, we investigated motor evoked potentials (MEPs in a moving muscle induced by transcranial magnetic stimulation during a go/stop/re-go task. In re-go trials with a short SRSI (100 ms, the MEP amplitude continued to decrease after the re-go-signal onset, indicating that stop-and-restart difficulties with short SRSIs might be associated with a neural mechanism in the human motor system, namely, stop-related suppression of corticomotor (CM excitability. Finally, we recorded electroencephalogram (EEG activity during a go/stop/re-go task and performed a single-trial-based EEG power and phase time-frequency analysis. Alpha-band EEG phase locking to re-go-signal, which was only observed in re-go trials with long SRSI (250 ms, weakened in the delayed re-go response trials. These EEG phase dynamics indicate an association between stop-and-restart difficulties with long SRSIs and a neural mechanism in the human perception system, namely, decreased probability of EEG phase locking to visual stimuli. In contrast, smooth stop-and-restart human movement can be achieved in re-go trials with sufficient SRSI (150-200 ms, because release of stop-related suppression and simultaneous counter-activation of CM excitability may occur as a single task without second re-go-signal perception. These results

  16. Neural mechanisms underlying stop-and-restart difficulties: involvement of the motor and perceptual systems.

    Science.gov (United States)

    Yamanaka, Kentaro; Nozaki, Daichi

    2013-01-01

    The ability to suddenly stop a planned movement or a movement being performed and restart it after a short interval is an important mechanism that allows appropriate behavior in response to contextual or environmental changes. However, performing such stop-and-restart movements smoothly is difficult at times. We investigated performance (response time) of stop-and-restart movements using a go/stop/re-go task and found consistent stop-and-restart difficulties after short (~100 ms) stop-to-restart intervals (SRSI), and an increased probability of difficulties after longer (>200 ms) SRSIs, suggesting that two different mechanisms underlie stop-and-restart difficulties. Next, we investigated motor evoked potentials (MEPs) in a moving muscle induced by transcranial magnetic stimulation during a go/stop/re-go task. In re-go trials with a short SRSI (100 ms), the MEP amplitude continued to decrease after the re-go-signal onset, indicating that stop-and-restart difficulties with short SRSIs might be associated with a neural mechanism in the human motor system, namely, stop-related suppression of corticomotor (CM) excitability. Finally, we recorded electroencephalogram (EEG) activity during a go/stop/re-go task and performed a single-trial-based EEG power and phase time-frequency analysis. Alpha-band EEG phase locking to re-go-signal, which was only observed in re-go trials with long SRSI (250 ms), weakened in the delayed re-go response trials. These EEG phase dynamics indicate an association between stop-and-restart difficulties with long SRSIs and a neural mechanism in the human perception system, namely, decreased probability of EEG phase locking to visual stimuli. In contrast, smooth stop-and-restart human movement can be achieved in re-go trials with sufficient SRSI (150-200 ms), because release of stop-related suppression and simultaneous counter-activation of CM excitability may occur as a single task without second re-go-signal perception. These results suggest that

  17. A longitudinal analysis of neural regions involved in reading the mind in the eyes.

    Science.gov (United States)

    Overgaauw, Sandy; van Duijvenvoorde, Anna C K; Gunther Moor, Bregtje; Crone, Eveline A

    2015-05-01

    The ability to perceive social intentions from people's eyes is present from an early age, yet little is known about whether this skill is fully developed in childhood or that subtle changes may still occur across adolescence. This fMRI study investigated the ability to read mental states by using an adapted version of the Reading the Mind in the Eyes task within adolescents (aged 12-19 years) over a 2-year test-retest interval. This longitudinal setup provides the opportunity to study both stability over time as well as age-related changes. The behavioral results showed that participants who performed well in the mental state condition at the first measurement also performed well at the second measurement. fMRI results revealed positive test-retest correlations of neural activity in the right superior temporal sulcus and right inferior frontal gyrus for the contrast mental state > control, suggesting stability within individuals over time. Besides stability of activation, dorsal medial prefrontal cortex showed a dip in mid-adolescence for the mental state > control condition and right inferior frontal gyrus decreased linearly with age for the mental state > control condition. These findings underline changes in the slope of the developmental pattern depending on age, even in the existence of relatively stable activation in the social brain network. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Let7a involves in neural stem cell differentiation relating with TLX level.

    Science.gov (United States)

    Song, Juhyun; Cho, Kyoung Joo; Oh, Yumi; Lee, Jong Eun

    2015-07-10

    Neural stem cells (NSCs) have the potential for differentiation into neurons known as a groundbreaking therapeutic solution for central nervous system (CNS) diseases. To resolve the therapeutic efficiency of NSCs, recent researchers have focused on the study on microRNA's role in CNS. Some micro RNAs have been reported significant functions in NSC self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. MicroRNA-Let7a (Let7a) has known as the regulator of diverse cellular mechanisms including cell differentiation and proliferation. In present study, we investigated whether Let7a regulates NSC differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. We performed the following experiments: western blot analysis, TaqMan assay, RT-PCR, and immunocytochemistry to confirm the alteration of NSCs. Our data showed that let7a play important roles in controlling NSC fate determination. Thus, manipulating Let-7A and TLX could be a novel strategy to enhance the efficiency of NSC's neuronal differentiation for CNS disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors.

    Science.gov (United States)

    Wei, Hongen; Chadman, Kathryn K; McCloskey, Daniel P; Sheikh, Ashfaq M; Malik, Mazhar; Brown, W Ted; Li, Xiaohong

    2012-06-01

    Abnormal immune responses have been reported to be associated with autism. A number of studies showed that cytokines were increased in the blood, brain, and cerebrospinal fluid of autistic subjects. Elevated IL-6 in autistic brain has been a consistent finding. However, the mechanisms by which IL-6 may be involved in the pathogenesis of autism are not well understood. Here we show that mice with elevated IL-6 in the brain display many autistic features, including impaired cognitive abilities, deficits in learning, abnormal anxiety traits and habituations, as well as decreased social interactions. IL-6 elevation caused alterations in excitatory and inhibitory synaptic formations and disrupted the balance of excitatory/inhibitory synaptic transmissions. IL-6 elevation also resulted in an abnormal change in the shape, length and distributing pattern of dendritic spines. These findings suggest that IL-6 elevation in the brain could mediate autistic-like behaviors, possibly through the imbalances of neural circuitry and impairments of synaptic plasticity. Published by Elsevier B.V.

  20. A study on the possible involvement of the PAX3 gene in human neural tube defects

    Energy Technology Data Exchange (ETDEWEB)

    Hol, F.A.; Hamel, B.C.J.; Geurds, M.P.A. [University Hospital Nijmegen (Netherlands)] [and others

    1994-09-01

    Neural tube defects (NTD) are congenital malformations of the central nervous system which are generally attributed to a combination of environmental and genetic factors. Recently, the molecular defect responsible for the phenotype of the Splotch mouse, a monogenic model system for NTD, was determined. A mutation disrupts the homeodomain of the gene for Pax3. In humans, mutations in the cognate gene for PAX3 can cause Waardenburg syndrome (WS), which is associated with NTD. Based on these findings, PAX3 can be regarded as a candidate gene for human NTD. To test this hypothesis we have screened the DNA of 39 familial and 70 sporadic NTD patients for mutations in the coding exons and flanking intron sequences of the PAX3 gene. SSC analysis revealed abnormal bands in exon 2, exon 5, exon 6 and exon 7 in different patients. A missense mutation was identified in exon 6 downstream from the homeodomain in several patients resulting in an amino acid substitution (Thr315Lys) in the protein. However, the same substitution was detected in unaffected controls suggesting no biological significance. Above shifts most likely represent polymorphisms that are irrelevant for NTD. A conspicuous SSC-band shift was observed in exon 5 of one familial patient with spina bifida. Sequencing revealed that the patient was heterozygous for a 5 bp deletion upstream of the homeodomain. The deletion causes a frameshift, which leads to premature termination of translation. Mild characteristics of WS were detected in several members of the family including the index patient. DNA analysis showed co-segregation of the mutation with these symptoms. Although PAX3 mutations can increase the penetrance of NTD in families with WS, our results show that their presence is not sufficient to cause NTD.

  1. Perfusion imaging in Pusher syndrome to investigate the neural substrates involved in controlling upright body position.

    Directory of Open Access Journals (Sweden)

    Luca Francesco Ticini

    Full Text Available Brain damage may induce a dysfunction of upright body position termed "pusher syndrome". Patients with such disorder suffer from an alteration of their sense of body verticality. They experience their body as oriented upright when actually tilted nearly 20 degrees to the ipsilesional side. Pusher syndrome typically is associated with posterior thalamic stroke; less frequently with extra-thalamic lesions. This argued for a fundamental role of these structures in our control of upright body posture. Here we investigated whether such patients may show additional functional or metabolic abnormalities outside the areas of brain lesion. We investigated 19 stroke patients with thalamic or with extra-thalamic lesions showing versus not showing misperception of body orientation. We measured fluid-attenuated inversion-recovery (FLAIR imaging, diffusion-weighted imaging (DWI, and perfusion-weighted imaging (PWI. This allowed us to determine the structural damage as well as to identify the malperfused but structural intact tissue. Pusher patients with thalamic lesions did not show dysfunctional brain areas in addition to the ones found to be structurally damaged. In the pusher patients with extra-thalamic lesions, the thalamus was neither structurally damaged nor malperfused. Rather, these patients showed small regions of abnormal perfusion in the structurally intact inferior frontal gyrus, middle temporal gyrus, inferior parietal lobule, and parietal white matter. The results indicate that these extra-thalamic brain areas contribute to the network controlling upright body posture. The data also suggest that damage of the neural tissue in the posterior thalamus itself rather than additional malperfusion in distant cortical areas is associated with pusher syndrome. Hence, it seems as if the normal functioning of both extra-thalamic as well as posterior thalamic structures is integral to perceiving gravity and controlling upright body orientation in humans.

  2. Neural reuse: a fundamental organizational principle of the brain.

    Science.gov (United States)

    Anderson, Michael L

    2010-08-01

    An emerging class of theories concerning the functional structure of the brain takes the reuse of neural circuitry for various cognitive purposes to be a central organizational principle. According to these theories, it is quite common for neural circuits established for one purpose to be exapted (exploited, recycled, redeployed) during evolution or normal development, and be put to different uses, often without losing their original functions. Neural reuse theories thus differ from the usual understanding of the role of neural plasticity (which is, after all, a kind of reuse) in brain organization along the following lines: According to neural reuse, circuits can continue to acquire new uses after an initial or original function is established; the acquisition of new uses need not involve unusual circumstances such as injury or loss of established function; and the acquisition of a new use need not involve (much) local change to circuit structure (e.g., it might involve only the establishment of functional connections to new neural partners). Thus, neural reuse theories offer a distinct perspective on several topics of general interest, such as: the evolution and development of the brain, including (for instance) the evolutionary-developmental pathway supporting primate tool use and human language; the degree of modularity in brain organization; the degree of localization of cognitive function; and the cortical parcellation problem and the prospects (and proper methods to employ) for function to structure mapping. The idea also has some practical implications in the areas of rehabilitative medicine and machine interface design.

  3. A review of brain circuitries involved in stuttering

    Directory of Open Access Journals (Sweden)

    Anna eCraig-Mcquaide

    2014-11-01

    Full Text Available Stuttering has been the subject of much research, nevertheless its aetiology remains incompletely understood. This article presents a critical review of the literature on stuttering, with particular reference to the role of the basal ganglia. Neuroimaging and lesion studies of developmental and acquired stuttering, as well as pharmacological and genetic studies are discussed. Evidence that stuttering of structural and functional changes in the basal ganglia in those who stutter indicates that this motor speech disorder is due, at least in part, to abnormal basal ganglia cues for the initiation and termination of articulatory movements. Studies discussed provide evidence of a dysfunctional hyperdopaminergic state of the thalamocortical pathways underlying speech motor control in stuttering. Evidence that stuttering can improve, worsen or recur following deep brain stimulation (DBS for other indications is presented in order to emphasise the role of basal ganglia in stuttering. Further research is needed to fully elucidate the pathophysiology of this speech disorder, which is associated with significant social isolation.

  4. A review of brain circuitries involved in stuttering

    Science.gov (United States)

    Craig-McQuaide, Anna; Akram, Harith; Zrinzo, Ludvic; Tripoliti, Elina

    2014-01-01

    Stuttering has been the subject of much research, nevertheless its etiology remains incompletely understood. This article presents a critical review of the literature on stuttering, with particular reference to the role of the basal ganglia (BG). Neuroimaging and lesion studies of developmental and acquired stuttering, as well as pharmacological and genetic studies are discussed. Evidence of structural and functional changes in the BG in those who stutter indicates that this motor speech disorder is due, at least in part, to abnormal BG cues for the initiation and termination of articulatory movements. Studies discussed provide evidence of a dysfunctional hyperdopaminergic state of the thalamocortical pathways underlying speech motor control in stuttering. Evidence that stuttering can improve, worsen or recur following deep brain stimulation for other indications is presented in order to emphasize the role of BG in stuttering. Further research is needed to fully elucidate the pathophysiology of this speech disorder, which is associated with significant social isolation. PMID:25452719

  5. Neural Signatures of the Reading-Writing Connection: Greater Involvement of Writing in Chinese Reading than English Reading.

    Science.gov (United States)

    Cao, Fan; Perfetti, Charles A

    2016-01-01

    Research on cross-linguistic comparisons of the neural correlates of reading has consistently found that the left middle frontal gyrus (MFG) is more involved in Chinese than in English. However, there is a lack of consensus on the interpretation of the language difference. Because this region has been found to be involved in writing, we hypothesize that reading Chinese characters involves this writing region to a greater degree because Chinese speakers learn to read by repeatedly writing the characters. To test this hypothesis, we recruited English L1 learners of Chinese, who performed a reading task and a writing task in each language. The English L1 sample had learned some Chinese characters through character-writing and others through phonological learning, allowing a test of writing-on-reading effect. We found that the left MFG was more activated in Chinese than English regardless of task, and more activated in writing than in reading regardless of language. Furthermore, we found that this region was more activated for reading Chinese characters learned by character-writing than those learned by phonological learning. A major conclusion is that writing regions are also activated in reading, and that this reading-writing connection is modulated by the learning experience. We replicated the main findings in a group of native Chinese speakers, which excluded the possibility that the language differences observed in the English L1 participants were due to different language proficiency level.

  6. Neural Signatures of the Reading-Writing Connection: Greater Involvement of Writing in Chinese Reading than English Reading.

    Directory of Open Access Journals (Sweden)

    Fan Cao

    Full Text Available Research on cross-linguistic comparisons of the neural correlates of reading has consistently found that the left middle frontal gyrus (MFG is more involved in Chinese than in English. However, there is a lack of consensus on the interpretation of the language difference. Because this region has been found to be involved in writing, we hypothesize that reading Chinese characters involves this writing region to a greater degree because Chinese speakers learn to read by repeatedly writing the characters. To test this hypothesis, we recruited English L1 learners of Chinese, who performed a reading task and a writing task in each language. The English L1 sample had learned some Chinese characters through character-writing and others through phonological learning, allowing a test of writing-on-reading effect. We found that the left MFG was more activated in Chinese than English regardless of task, and more activated in writing than in reading regardless of language. Furthermore, we found that this region was more activated for reading Chinese characters learned by character-writing than those learned by phonological learning. A major conclusion is that writing regions are also activated in reading, and that this reading-writing connection is modulated by the learning experience. We replicated the main findings in a group of native Chinese speakers, which excluded the possibility that the language differences observed in the English L1 participants were due to different language proficiency level.

  7. The influence of group membership on the neural correlates involved in empathy.

    Directory of Open Access Journals (Sweden)

    Robert eEres

    2013-05-01

    Full Text Available Empathy involves affective, cognitive and emotion regulative components. The affective component relies on the sharing of emotional states with others and is discussed here in relation to the human Mirror System. On the other hand, the cognitive component is related to understanding the mental states of others and draws upon literature surrounding Theory of Mind. The final component, emotion regulation depends on executive function and is responsible for managing the degree to which explicit empathic responses are made. This mini-review provides information on how each of the three components is individually affected by group membership and how this leads to in-group bias.

  8. The influence of group membership on the neural correlates involved in empathy.

    Science.gov (United States)

    Eres, Robert; Molenberghs, Pascal

    2013-01-01

    Empathy involves affective, cognitive, and emotion regulative components. The affective component relies on the sharing of emotional states with others and is discussed here in relation to the human Mirror System. On the other hand, the cognitive component is related to understanding the mental states of others and draws upon literature surrounding Theory of Mind (ToM). The final component, emotion regulation, depends on executive function and is responsible for managing the degree to which explicit empathic responses are made. This mini-review provides information on how each of the three components is individually affected by group membership and how this leads to in-group bias.

  9. Lithium promotes neural precursor cell proliferation: evidence for the involvement of the non-canonical GSK-3β-NF-AT signaling

    Directory of Open Access Journals (Sweden)

    Qu Zhaoxia

    2011-05-01

    Full Text Available Abstract Lithium, a drug that has long been used to treat bipolar disorder and some other human pathogenesis, has recently been shown to stimulate neural precursor growth. However, the involved mechanism is not clear. Here, we show that lithium induces proliferation but not survival of neural precursor cells. Mechanistic studies suggest that the effect of lithium mainly involved activation of the transcription factor NF-AT and specific induction of a subset of proliferation-related genes. While NF-AT inactivation by specific inhibition of its upstream activator calcineurin antagonized the effect of lithium on the proliferation of neural precursor cells, specific inhibition of the NF-AT inhibitor GSK-3β, similar to lithium treatment, promoted neural precursor cell proliferation. One important function of lithium appeared to increase inhibitory phosphorylation of GSK-3β, leading to GSK-3β suppression and subsequent NF-AT activation. Moreover, lithium-induced proliferation of neural precursor cells was independent of its role in inositol depletion. These findings not only provide mechanistic insights into the clinical effects of lithium, but also suggest an alternative therapeutic strategy for bipolar disorder and other neural diseases by targeting the non-canonical GSK-3β-NF-AT signaling.

  10. The development of micromachined gyroscope structure and circuitry technology.

    Science.gov (United States)

    Xia, Dunzhu; Yu, Cheng; Kong, Lun

    2014-01-14

    This review surveys micromachined gyroscope structure and circuitry technology. The principle of micromachined gyroscopes is first introduced. Then, different kinds of MEMS gyroscope structures, materials and fabrication technologies are illustrated. Micromachined gyroscopes are mainly categorized into micromachined vibrating gyroscopes (MVGs), piezoelectric vibrating gyroscopes (PVGs), surface acoustic wave (SAW) gyroscopes, bulk acoustic wave (BAW) gyroscopes, micromachined electrostatically suspended gyroscopes (MESGs), magnetically suspended gyroscopes (MSGs), micro fiber optic gyroscopes (MFOGs), micro fluid gyroscopes (MFGs), micro atom gyroscopes (MAGs), and special micromachined gyroscopes. Next, the control electronics of micromachined gyroscopes are analyzed. The control circuits are categorized into typical circuitry and special circuitry technologies. The typical circuitry technologies include typical analog circuitry and digital circuitry, while the special circuitry consists of sigma delta, mode matching, temperature/quadrature compensation and novel special technologies. Finally, the characteristics of various typical gyroscopes and their development tendency are discussed and investigated in detail.

  11. The Development of Micromachined Gyroscope Structure and Circuitry Technology

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    Dunzhu Xia

    2014-01-01

    Full Text Available This review surveys micromachined gyroscope structure and circuitry technology. The principle of micromachined gyroscopes is first introduced. Then, different kinds of MEMS gyroscope structures, materials and fabrication technologies are illustrated. Micromachined gyroscopes are mainly categorized into micromachined vibrating gyroscopes (MVGs, piezoelectric vibrating gyroscopes (PVGs, surface acoustic wave (SAW gyroscopes, bulk acoustic wave (BAW gyroscopes, micromachined electrostatically suspended gyroscopes (MESGs, magnetically suspended gyroscopes (MSGs, micro fiber optic gyroscopes (MFOGs, micro fluid gyroscopes (MFGs, micro atom gyroscopes (MAGs, and special micromachined gyroscopes. Next, the control electronics of micromachined gyroscopes are analyzed. The control circuits are categorized into typical circuitry and special circuitry technologies. The typical circuitry technologies include typical analog circuitry and digital circuitry, while the special circuitry consists of sigma delta, mode matching, temperature/quadrature compensation and novel special technologies. Finally, the characteristics of various typical gyroscopes and their development tendency are discussed and investigated in detail.

  12. Reading acceleration training changes brain circuitry in children with reading difficulties

    Science.gov (United States)

    Horowitz-Kraus, Tzipi; Vannest, Jennifer J; Kadis, Darren; Cicchino, Nicole; Wang, Yingying Y; Holland, Scott K

    2014-01-01

    Introduction Dyslexia is characterized by slow, inaccurate reading. Previous studies have shown that the Reading Acceleration Program (RAP) improves reading speed and accuracy in children and adults with dyslexia and in typical readers across different orthographies. However, the effect of the RAP on the neural circuitry of reading has not been established. In the current study, we examined the effect of the RAP training on regions of interest in the neural circuitry for reading using a lexical decision task during fMRI in children with reading difficulties and typical readers. Methods Children (8–12 years old) with reading difficulties and typical readers were studied before and after 4 weeks of training with the RAP in both groups. Results In addition to improvements in oral and silent contextual reading speed, training-related gains were associated with increased activation of the left hemisphere in both children with reading difficulties and typical readers. However, only children with reading difficulties showed improvements in reading comprehension, which were associated with significant increases in right frontal lobe activation. Conclusions Our results demonstrate differential effects of the RAP on neural circuits supporting reading in both children with reading difficulties and typical readers and suggest that the intervention may stimulate use of typical neural circuits for reading and engage compensatory pathways to support reading in the developing brain of children with reading difficulties. PMID:25365797

  13. Reading acceleration training changes brain circuitry in children with reading difficulties.

    Science.gov (United States)

    Horowitz-Kraus, Tzipi; Vannest, Jennifer J; Kadis, Darren; Cicchino, Nicole; Wang, Yingying Y; Holland, Scott K

    2014-01-01

    Dyslexia is characterized by slow, inaccurate reading. Previous studies have shown that the Reading Acceleration Program (RAP) improves reading speed and accuracy in children and adults with dyslexia and in typical readers across different orthographies. However, the effect of the RAP on the neural circuitry of reading has not been established. In the current study, we examined the effect of the RAP training on regions of interest in the neural circuitry for reading using a lexical decision task during fMRI in children with reading difficulties and typical readers. Children (8-12 years old) with reading difficulties and typical readers were studied before and after 4 weeks of training with the RAP in both groups. In addition to improvements in oral and silent contextual reading speed, training-related gains were associated with increased activation of the left hemisphere in both children with reading difficulties and typical readers. However, only children with reading difficulties showed improvements in reading comprehension, which were associated with significant increases in right frontal lobe activation. Our results demonstrate differential effects of the RAP on neural circuits supporting reading in both children with reading difficulties and typical readers and suggest that the intervention may stimulate use of typical neural circuits for reading and engage compensatory pathways to support reading in the developing brain of children with reading difficulties.

  14. Neural overlap in processing music and speech

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    Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L.

    2015-01-01

    Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. PMID:25646513

  15. Dopamine elevates and lowers astroglial Ca2+ through distinct pathways depending on local synaptic circuitry.

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    Jennings, Alistair; Tyurikova, Olga; Bard, Lucie; Zheng, Kaiyu; Semyanov, Alexey; Henneberger, Christian; Rusakov, Dmitri A

    2017-03-01

    Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca2+ rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca2+ in cells connected via gap junctions to astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca2+ ] measurements, we also employed life-time imaging of the Ca2+ indicator Oregon Green BAPTA-1. We found that dopamine triggered a dose-dependent, bidirectional Ca2+ response in stratum radiatum astroglia, a jagged elevation accompanied and followed by below-baseline decreases. The elevation depended on D1/D2 receptors and engaged intracellular Ca2+ storage and removal whereas the dopamine-induced [Ca2+ ] decrease involved D2 receptors only and was sensitive to Ca2+ channel blockade. In contrast, the stratum lacunosum moleculare astroglia generated higher-threshold dopamine-induced Ca2+ responses which did not depend on dopamine receptors and were uncoupled from the prominent inhibitory action of dopamine on local perforant path synapses. Our findings thus suggest that a single neurotransmitter-dopamine-could either elevate or decrease astrocyte [Ca2+ ] depending on the receptors involved, that such actions are specific to the regional neural circuitry and that they may be causally uncoupled from dopamine actions on local synapses. The results also indicate that [Ca2+ ] elevations commonly detected in astroglia can represent the variety of distinct mechanisms acting on the microscopic scale. GLIA 2017;65:447-459. © 2016 The Authors Glia Published by Wiley Periodicals, Inc.

  16. Functional maps of neocortical local circuitry

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    Alex M Thomson

    2007-10-01

    Full Text Available This review aims to summarize data obtained with different techniques to provide a functional map of the local circuit connections made by neocortical neurones, a reference for those interested in cortical circuitry and the numerical information required by those wishing to model the circuit. A brief description of the main techniques used to study circuitry is followed by outline descriptions of the major classes of neocortical excitatory and inhibitory neurones and the connections that each layer makes with other cortical and subcortical regions. Maps summarizing the projection patterns of each class of neurone within the local circuit and tables of the properties of these local circuit connections are provided.This review relies primarily on anatomical studies that have identified the classes of neurones and their local and long distance connections and on paired intracellular and whole-cell recordings which have documented the properties of the connections between them. A large number of different types of synaptic connections have been described, but for some there are only a few published examples and for others the details that can only be obtained with paired recordings and dye-filling are lacking. A further complication is provided by the range of species, technical approaches and age groups used in these studies. Wherever possible the range of available data are summarised and compared. To fill some of the more obvious gaps for the less well-documented cases, data obtained with other methods are also summarized.

  17. Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry.

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    Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo

    2017-01-01

    Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2(fl)°(x) conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

  18. Immediate Neural Plasticity Involving Reaction Time in a Saccadic Eye Movement Task is Intact in Children With Fetal Alcohol Spectrum Disorder.

    Science.gov (United States)

    Paolozza, Angelina; Munoz, Douglas P; Brien, Donald; Reynolds, James N

    2016-11-01

    Saccades are rapid eye movements that bring an image of interest onto the retina. Previous research has found that in healthy individuals performing eye movement tasks, the location of a previous visual target can influence performance of the saccade on the next trial. This rapid behavioral adaptation represents a form of immediate neural plasticity within the saccadic circuitry. Our studies have shown that children with fetal alcohol spectrum disorder (FASD) are impaired on multiple saccade measures. We therefore investigated these previous trial effects in typically developing children and children with FASD to measure sensory neural plasticity and how these effects vary with age and pathology. Both typically developing control children (n = 102; mean age = 10.54 ± 3.25; 48 males) and children with FASD (n = 66; mean age = 11.85 ± 3.42; 35 males) were recruited from 5 sites across Canada. Each child performed a visually guided saccade task. Reaction time and saccade amplitude were analyzed and then assessed based on the previous trial. There was a robust previous trial effect for both reaction time and amplitude, with both the control and FASD groups displaying faster reaction times and smaller saccades during alternation trials (visual target presented on the opposite side to the previous trial). Children with FASD exhibited smaller overall mean amplitude and smaller amplitude selectively on alternation trials compared with controls. The effect of the previous trial on reaction time and amplitude did not differ across childhood and adolescent development. Children with FASD did not display any significant reaction time differences, despite exhibiting numerous deficits in motor and higher level cognitive control over saccades in other studies. These results suggest that this form of immediate neural plasticity in response to sensory information before saccade initiation remains intact in children with FASD. In contrast, the previous trial effect on

  19. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    Science.gov (United States)

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  20. Functional Circuitry Effect of Ventral Tegmental Area Deep Brain Stimulation: Imaging and Neurochemical Evidence of Mesocortical and Mesolimbic Pathway Modulation.

    Science.gov (United States)

    Settell, Megan L; Testini, Paola; Cho, Shinho; Lee, Jannifer H; Blaha, Charles D; Jo, Hang J; Lee, Kendall H; Min, Hoon-Ki

    2017-01-01

    Background: The ventral tegmental area (VTA), containing mesolimbic and mesocortical dopaminergic neurons, is implicated in processes involving reward, addiction, reinforcement, and learning, which are associated with a variety of neuropsychiatric disorders. Electrical stimulation of the VTA or the medial forebrain bundle and its projection target the nucleus accumbens (NAc) is reported to improve depressive symptoms in patients affected by severe, treatment-resistant major depressive disorder (MDD) and depressive-like symptoms in animal models of depression. Here we sought to determine the neuromodulatory effects of VTA deep brain stimulation (DBS) in a normal large animal model (swine) by combining neurochemical measurements with functional magnetic resonance imaging (fMRI). Methods: Animals (n = 8 swine) were implanted with a unilateral DBS electrode targeting the VTA. During stimulation (130 Hz frequency, 0.25 ms pulse width, and 3 V amplitude), fMRI was performed. Following fMRI, fast-scan cyclic voltammetry in combination with carbon fiber microelectrodes was performed to quantify VTA-DBS-evoked dopamine release in the ipsilateral NAc. In a subset of swine, the blood oxygen level-dependent (BOLD) percent change evoked by stimulation was performed at increasing voltages (1, 2, and 3 V). Results: A significant increase in VTA-DBS-evoked BOLD signal was found in the following regions: the ipsilateral dorsolateral prefrontal cortex, anterior and posterior cingulate, insula, premotor cortex, primary somatosensory cortex, and striatum. A decrease in the BOLD signal was also observed in the contralateral parahippocampal cortex, dorsolateral and anterior prefrontal cortex, insula, inferior temporal gyrus, and primary somatosensory cortex (Bonferroni-corrected modulation of the neural circuitry associated with VTA-DBS was characterized in a large animal. Our findings suggest that VTA-DBS could affect the activity of neural systems and brain regions implicated in

  1. Neural systems and hormones mediating attraction to infant and child faces

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    Lizhu eLuo

    2015-07-01

    Full Text Available We find infant faces highly attractive as a result of specific features which Konrad Lorenz termed Kindchenschema or baby schema, and this is considered to be an important adaptive trait for promoting protective and caregiving behaviors in adults, thereby increasing the chances of infant survival. This review first examines the behavioral support for this effect and physical and behavioral factors which can influence it. It next reviews the increasing number of neuroimaging and electrophysiological studies investigating the neural circuitry underlying this baby schema effect in both parents and non-parents of both sexes. Next it considers potential hormonal contributions to the baby schema effect in both sexes and then neural effects associated with reduced responses to infant cues in post-partum depression, anxiety and drug taking. Overall the findings reviewed reveal a very extensive neural circuitry involved in our perception of cutenessin infant faces with enhanced activation compared to adult faces being found in brain regions involved in face perception, attention, emotion, empathy, memory, reward and attachment, theory of mind and also control of motor responses.Both mothers and fathers also show evidence for enhanced responses in these same neural systems when viewing their own as opposed to another child. Furthermore, responses to infant cues in many of these neural systems are reduced in mothers with post-partum depression or anxiety or have taken addictive drugs throughout pregnancy. In general reproductively active women tend to rate infant faces as cuter than men, which may reflect both heightened attention to relevant cues and a stronger activation in their brain reward circuitry. Perception of infant cuteness may also be influenced by reproductive hormones with the hypothalamic neuropeptide oxytocin being most strongly associated to date with increased attention andattractionto infant cues in both sexes.

  2. Neural Differentiation of Human Adipose Tissue-Derived Stem Cells Involves Activation of the Wnt5a/JNK Signalling

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    Sujeong Jang

    2015-01-01

    Full Text Available Stem cells are a powerful resource for cell-based transplantation therapies, but understanding of stem cell differentiation at the molecular level is not clear yet. We hypothesized that the Wnt pathway controls stem cell maintenance and neural differentiation. We have characterized the transcriptional expression of Wnt during the neural differentiation of hADSCs. After neural induction, the expressions of Wnt2, Wnt4, and Wnt11 were decreased, but the expression of Wnt5a was increased compared with primary hADSCs in RT-PCR analysis. In addition, the expression levels of most Fzds and LRP5/6 ligand were decreased, but not Fzd3 and Fzd5. Furthermore, Dvl1 and RYK expression levels were downregulated in NI-hADSCs. There were no changes in the expression of ß-catenin and GSK3ß. Interestingly, Wnt5a expression was highly increased in NI-hADSCs by real time RT-PCR analysis and western blot. Wnt5a level was upregulated after neural differentiation and Wnt3, Dvl2, and Naked1 levels were downregulated. Finally, we found that the JNK expression was increased after neural induction and ERK level was decreased. Thus, this study shows for the first time how a single Wnt5a ligand can activate the neural differentiation pathway through the activation of Wnt5a/JNK pathway by binding Fzd3 and Fzd5 and directing Axin/GSK-3ß in hADSCs.

  3. Précis of Neural organization: structure, function, and dynamics.

    Science.gov (United States)

    Arbib, M A; Erdi, P

    2000-08-01

    NEURAL ORGANIZATION: Structure, function, and dynamics shows how theory and experiment can supplement each other in an integrated, evolving account of the brain's structure, function, and dynamics. (1) STRUCTURE: Studies of brain function and dynamics build on and contribute to an understanding of many brain regions, the neural circuits that constitute them, and their spatial relations. We emphasize Szentágothai's modular architectonics principle, but also stress the importance of the microcomplexes of cerebellar circuitry and the lamellae of hippocampus. (2) FUNCTION: Control of eye movements, reaching and grasping, cognitive maps, and the roles of vision receive a functional decomposition in terms of schemas. Hypotheses as to how each schema is implemented through the interaction of specific brain regions provide the basis for modeling the overall function by neural networks constrained by neural data. Synthetic PET integrates modeling of primate circuitry with data from human brain imaging. (3) DYNAMICS: Dynamic system theory analyzes spatiotemporal neural phenomena, such as oscillatory and chaotic activity in both single neurons and (often synchronized) neural networks, the self-organizing development and plasticity of ordered neural structures, and learning and memory phenomena associated with synaptic modification. Rhythm generation involves multiple levels of analysis, from intrinsic cellular processes to loops involving multiple brain regions. A variety of rhythms are related to memory functions. The Précis presents a multifaceted case study of the hippocampus. We conclude with the claim that language and other cognitive processes can be fruitfully studied within the framework of neural organization that the authors have charted with John Szentágothai.

  4. [Glutamate signaling and neural plasticity].

    Science.gov (United States)

    Watanabe, Masahiko

    2013-07-01

    Proper functioning of the nervous system relies on the precise formation of neural circuits during development. At birth, neurons have redundant synaptic connections not only to their proper targets but also to other neighboring cells. Then, functional neural circuits are formed during early postnatal development by the selective strengthening of necessary synapses and weakening of surplus connections. Synaptic connections are also modified so that projection fields of active afferents expand at the expense of lesser ones. We have studied the molecular mechanisms underlying these activity-dependent prunings and the plasticity of synaptic circuitry using gene-engineered mice defective in the glutamatergic signaling system. NMDA-type glutamate receptors are critically involved in the establishment of the somatosensory pathway ascending from the brainstem trigeminal nucleus to the somatosensory cortex. Without NMDA receptors, whisker-related patterning fails to develop, whereas lesion-induced plasticity occurs normally during the critical period. In contrast, mice lacking the glutamate transporters GLAST or GLT1 are selectively impaired in the lesion-induced critical plasticity of cortical barrels, although whisker-related patterning itself develops normally. In the developing cerebellum, multiple climbing fibers initially innervating given Purkinje cells are eliminated one by one until mono-innervation is achieved. In this pruning process, P/Q-type Ca2+ channels expressed on Purkinje cells are critically involved by the selective strengthening of single main climbing fibers against other lesser afferents. Therefore, the activation of glutamate receptors that leads to an activity-dependent increase in the intracellular Ca2+ concentration plays a key role in the pruning of immature synaptic circuits into functional circuits. On the other hand, glutamate transporters appear to control activity-dependent plasticity among afferent fields, presumably through adjusting

  5. Lessons from sleeping flies: insights from Drosophila melanogaster on the neuronal circuitry and importance of sleep.

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    Potdar, Sheetal; Sheeba, Vasu

    2013-06-01

    Sleep is a highly conserved behavior whose role is as yet unknown, although it is widely acknowledged as being important. Here we provide an overview of many vital questions regarding this behavior, that have been addressed in recent years using the genetically tractable model organism Drosophila melanogaster in several laboratories around the world. Rest in D. melanogaster has been compared to mammalian sleep and its homeostatic and circadian regulation have been shown to be controlled by intricate neuronal circuitry involving circadian clock neurons, mushroom bodies, and pars intercerebralis, although their exact roles are not entirely clear. We draw attention to the yet unanswered questions and contradictions regarding the nature of the interactions between the brain regions implicated in the control of sleep. Dopamine, octopamine, γ-aminobutyric acid (GABA), and serotonin are the chief neurotransmitters identified as functioning in different limbs of this circuit, either promoting arousal or sleep by modulating membrane excitability of underlying neurons. Some studies have suggested that certain brain areas may contribute towards both sleep and arousal depending on activation of specific subsets of neurons. Signaling pathways implicated in the sleep circuit include cyclic adenosine monophosphate (cAMP) and epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) signaling pathways that operate on different neural substrates. Thus, this field of research appears to be on the cusp of many new and exciting findings that may eventually help in understanding how this complex physiological phenomenon is modulated by various neuronal circuits in the brain. Finally, some efforts to approach the "Holy Grail" of why we sleep have been summarized.

  6. Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia.

    Science.gov (United States)

    Loggia, Marco L; Berna, Chantal; Kim, Jieun; Cahalan, Christine M; Gollub, Randy L; Wasan, Ajay D; Harris, Richard E; Edwards, Robert R; Napadow, Vitaly

    2014-01-01

    While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief. Thirty-one FM patients and 14 controls underwent functional magnetic resonance imaging, while receiving cuff pressure pain stimuli on the leg calibrated to elicit a pain rating of ~50 on a 100-point scale. During the scan, subjects also received visual cues informing them of the impending onset of pain (pain anticipation) and the impending offset of pain (relief anticipation). Patients exhibited less robust activation during both anticipation of pain and anticipation of relief within regions of the brain commonly thought to be involved in sensory, affective, cognitive, and pain-modulatory processes. In healthy controls, direct searches and region-of-interest analyses of the ventral tegmental area revealed a pattern of activity compatible with the encoding of punishment signals: activation during anticipation of pain and pain stimulation, but deactivation during anticipation of pain relief. In FM patients, however, activity in the ventral tegmental area during periods of pain and periods of anticipation (of both pain and relief) was dramatically reduced or abolished. FM patients exhibit disrupted brain responses to reward/punishment. The ventral tegmental area is a source of reward-linked dopaminergic/γ-aminobutyric acid-releasing (GABAergic) neurotransmission in the brain, and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may be related to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients. Copyright © 2014 by the American

  7. Mapping the brain's metaphor circuitry: metaphorical thought in everyday reason

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    Lakoff, George

    2014-01-01

    An overview of the basics of metaphorical thought and language from the perspective of Neurocognition, the integrated interdisciplinary study of how conceptual thought and language work in the brain. The paper outlines a theory of metaphor circuitry and discusses how everyday reason makes use of embodied metaphor circuitry. PMID:25566012

  8. Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

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    Elisa M. Nabel

    2013-11-01

    Full Text Available Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development –the preeminent model of experience-dependent critical period plasticity- actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins– endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

  9. Poor ability to resist tempting calorie rich food is linked to altered balance between neural systems involved in urge and self-control

    OpenAIRE

    He, Qinghua; Xiao, Lin; Xue, Gui; Wong, Savio; Ames, Susan L.; Schembre, Susan M.; Bechara, Antoine

    2014-01-01

    Background The loss of self-control or inability to resist tempting/rewarding foods, and the development of less healthful eating habits may be explained by three key neural systems: (1) a hyper-functioning striatum system driven by external rewarding cues; (2) a hypo-functioning decision-making and impulse control system; and (3) an altered insula system involved in the translation of homeostatic and interoceptive signals into self-awareness and what may be subjectively experienced as a feel...

  10. Efficient genome editing of genes involved in neural crest development using the CRISPR/Cas9 system in Xenopus embryos.

    Science.gov (United States)

    Liu, Zhongzhen; Cheng, Tina Tsz Kwan; Shi, Zhaoying; Liu, Ziran; Lei, Yong; Wang, Chengdong; Shi, Weili; Chen, Xiongfeng; Qi, Xufeng; Cai, Dongqing; Feng, Bo; Deng, Yi; Chen, Yonglong; Zhao, Hui

    2016-01-01

    The RNA guided CRISPR/Cas9 nucleases have been proven to be effective for gene disruption in various animal models including Xenopus tropicalis. The neural crest (NC) is a transient cell population during embryonic development and contributes to a large variety of tissues. Currently, loss-of-function studies on NC development in X. tropicalis are largely based on morpholino antisense oligonucleotide. It is worthwhile establishing targeted gene knockout X. tropicails line using CRISPR/Cas9 system to study NC development. We utilized CRISPR/Cas9 to disrupt genes that are involved in NC formation in X. tropicalis embryos. A single sgRNA and Cas9 mRNA synthesized in vitro, were co-injected into X. tropicalis embryos at one-cell stage to induce single gene disruption. We also induced duplex mutations, large segmental deletions and inversions in X. tropicalis by injecting Cas9 and a pair of sgRNAs. The specificity of CRISPR/Cas9 was assessed in X. tropicalis embryos and the Cas9 nickase was used to reduce the off-target cleavages. Finally, we crossed the G0 mosaic frogs with targeted mutations to wild type frogs and obtained the germline transmission. Total 16 target sites in 15 genes were targeted by CRISPR/Cas9 and resulted in successful indel mutations at 14 loci with disruption efficiencies in a range from 9.3 to 57.8 %. Furthermore, we demonstrated the feasibility of generation of duplex mutations, large segmental deletions and inversions by using Cas9 and a pair of sgRNAs. We observed that CRISPR/Cas9 displays obvious off-target effects at some loci in X. tropicalis embryos. Such off-target cleavages was reduced by using the D10A Cas9 nickase. Finally, the Cas9 induced indel mutations were efficiently passed to G1 offspring. Our study proved that CRISPR/Cas9 could mediate targeted gene mutation in X. tropicalis with high efficiency. This study expands the application of CRISPR/Cas9 platform in X. tropicalis and set a basis for studying NC development using genetic

  11. Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa.

    Science.gov (United States)

    Holsen, Laura M; Lawson, Elizabeth A; Blum, Justine; Ko, Eunice; Makris, Nikos; Fazeli, Pouneh K; Klibanski, Anne; Goldstein, Jill M

    2012-09-01

    Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food's reward value and integration of these with

  12. Superconducting circuitry for quantum electromechanical systems

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    LaHaye, Matthew D.; Rouxinol, Francisco; Hao, Yu; Shim, Seung-Bo; Irish, Elinor K.

    2015-05-01

    Superconducting systems have a long history of use in experiments that push the frontiers of mechanical sensing. This includes both applied and fundamental research, which at present day ranges from quantum computing research and e orts to explore Planck-scale physics to fundamental studies on the nature of motion and the quantum limits on our ability to measure it. In this paper, we first provide a short history of the role of superconducting circuitry and devices in mechanical sensing, focusing primarily on efforts in the last decade to push the study of quantum mechanics to include motion on the scale of human-made structures. This background sets the stage for the remainder of the paper, which focuses on the development of quantum electromechanical systems (QEMS) that incorporate superconducting quantum bits (qubits), superconducting transmission line resonators and flexural nanomechanical elements. In addition to providing the motivation and relevant background on the physical behavior of these systems, we discuss our recent efforts to develop a particular type of QEMS that is based upon the Cooper-pair box (CPB) and superconducting coplanar waveguide (CPW) cavities, a system which has the potential to serve as a testbed for studying the quantum properties of motion in engineered systems.

  13. 40LoVe and Samba are involved in Xenopus neural development and functionally distinct from hnRNP AB.

    Directory of Open Access Journals (Sweden)

    Maria Andreou

    Full Text Available Heterogeneous nuclear ribonucleoproteins (hnRNPs comprise a large group of modular RNA-binding proteins classified according to their conserved domains. This modular nature, coupled with a large choice of alternative splice variants generates functional diversity. Here, we investigate the biological differences between 40LoVe, its splice variant Samba and its pseudoallele hnRNP AB in neural development. Loss of function experiments lead to defects in neural development with reduction of eye size, which stem primarily from increased apoptosis and reduced proliferation in neural tissues. Despite very high homology between 40LoVe/Samba and hnRNP AB, these proteins display major differences in localization, which appear to be in part responsible for functional differences. Specifically, we show that the 40Love/Samba carboxy-terminal domain (GRD enables nucleocytoplasmic shuttling behavior. This domain is slightly different in hnRNP AB, leading to nuclear-restricted localization. Finally, we show that shuttling is required for 40LoVe/Samba function in neural development.

  14. Prion replication occurs in endogenous adult neural stem cells and alters their neuronal fate: involvement of endogenous neural stem cells in prion diseases.

    Directory of Open Access Journals (Sweden)

    Aroa Relaño-Ginès

    Full Text Available Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease.

  15. Adolescent girls' neural response to reward mediates the relation between childhood financial disadvantage and depression.

    Science.gov (United States)

    Romens, Sarah E; Casement, Melynda D; McAloon, Rose; Keenan, Kate; Hipwell, Alison E; Guyer, Amanda E; Forbes, Erika E

    2015-11-01

    Children who experience socioeconomic disadvantage are at heightened risk for developing depression; however, little is known about neurobiological mechanisms underlying this association. Low socioeconomic status (SES) during childhood may confer risk for depression through its stress-related effects on the neural circuitry associated with processing monetary rewards. In a prospective study, we examined the relationships among the number of years of household receipt of public assistance from age 5-16 years, neural activation during monetary reward anticipation and receipt at age 16, and depression symptoms at age 16 in 123 girls. Number of years of household receipt of public assistance was positively associated with heightened response in the medial prefrontal cortex during reward anticipation, and this heightened neural response mediated the relationship between socioeconomic disadvantage and current depression symptoms, controlling for past depression. Chronic exposure to socioeconomic disadvantage in childhood may alter neural circuitry involved in reward anticipation in adolescence, which in turn may confer risk for depression. © 2015 Association for Child and Adolescent Mental Health.

  16. Adolescent girls’ neural response to reward mediates the relation between childhood financial disadvantage and depression

    Science.gov (United States)

    Romens, Sarah E.; Casement, Melynda D.; McAloon, Rose; Keenan, Kate; Hipwell, Alison E.; Guyer, Amanda E.; Forbes, Erika E.

    2015-01-01

    Background Children who experience socioeconomic disadvantage are at heightened risk for developing depression; however, little is known about neurobiological mechanisms underlying this association. Low socioeconomic status (SES) during childhood may confer risk for depression through its stress-related effects on the neural circuitry associated with processing monetary rewards. Methods In a prospective study, we examined the relationships among the number of years of household receipt of public assistance from age 5–16 years, neural activation during monetary reward anticipation and receipt at age 16, and depression symptoms at age 16 in 123 girls. Results Number of years of household receipt of public assistance was positively associated with heightened response in the medial prefrontal cortex during reward anticipation, and this heightened neural response mediated the relationship between socioeconomic disadvantage and current depression symptoms, controlling for past depression. Conclusions Chronic exposure to socioeconomic disadvantage in childhood may alter neural circuitry involved in reward anticipation in adolescence, which in turn may confer risk for depression. PMID:25846746

  17. Circuitry, systems and methods for detecting magnetic fields

    Science.gov (United States)

    Kotter, Dale K [Shelley, ID; Spencer, David F [Idaho Falls, ID; Roybal, Lyle G [Idaho Falls, ID; Rohrbaugh, David T [Idaho Falls, ID

    2010-09-14

    Circuitry for detecting magnetic fields includes a first magnetoresistive sensor and a second magnetoresistive sensor configured to form a gradiometer. The circuitry includes a digital signal processor and a first feedback loop coupled between the first magnetoresistive sensor and the digital signal processor. A second feedback loop which is discrete from the first feedback loop is coupled between the second magnetoresistive sensor and the digital signal processor.

  18. Micro- and Nanotechnologies for Optical Neural Interfaces

    Science.gov (United States)

    Pisanello, Ferruccio; Sileo, Leonardo; De Vittorio, Massimo

    2016-01-01

    In last decade, the possibility to optically interface with the mammalian brain in vivo has allowed unprecedented investigation of functional connectivity of neural circuitry. Together with new genetic and molecular techniques to optically trigger and monitor neural activity, a new generation of optical neural interfaces is being developed, mainly thanks to the exploitation of both bottom-up and top-down nanofabrication approaches. This review highlights the role of nanotechnologies for optical neural interfaces, with particular emphasis on new devices and methodologies for optogenetic control of neural activity and unconventional methods for detection and triggering of action potentials using optically-active colloidal nanoparticles. PMID:27013939

  19. Neural and sympathetic activity associated with exploration in decision-making: Further evidence for involvement of insula

    Directory of Open Access Journals (Sweden)

    Hideki eOhira

    2014-11-01

    Full Text Available We previously reported that sympathetic activity was associated with exploration in decision-making indexed by entropy, which is a concept in information theory and indexes randomness of choices or the degree of deviation from sticking to recent experiences of gains and losses, and that activation of the anterior insula mediated this association. The current study aims to replicate and to expand these findings in a situation where contingency between options and outcomes is manipulated. Sixteen participants performed a stochastic decision-making task in which we manipulated a condition with low uncertainty of gain/loss (contingent-reward condition and a condition with high uncertainty of gain/loss (random-reward condition. Regional cerebral blood flow was measured by 15O-water positron emission tomography (PET, and cardiovascular parameters and catecholamine in the peripheral blood were measured, during the task. In the contingent-reward condition, norepinephrine as an index of sympathetic activity was positively correlated with entropy indicating exploration in decision-making. Norepinephrine was negatively correlated with neural activity in the right posterior insula, rostral anterior cingulate cortex, and dorsal pons, suggesting neural bases for detecting changes of bodily states. Furthermore, right anterior insular activity was negatively correlated with entropy, suggesting influences on exploration in decision-making. By contrast, in the random-reward condition, entropy correlated with activity in the dorsolateral prefrontal and parietal cortices but not with sympathetic activity. These findings suggest that influences of sympathetic activity on exploration in decision-making and its underlying neural mechanisms might be dependent on the degree of uncertainty of situations.

  20. Effectiveness of a Treatment Involving Soft Tissue Techniques and/or Neural Mobilization Techniques in the Management of Tension-Type Headache: A Randomized Controlled Trial.

    Science.gov (United States)

    Ferragut-Garcías, Alejandro; Plaza-Manzano, Gustavo; Rodríguez-Blanco, Cleofás; Velasco-Roldán, Olga; Pecos-Martín, Daniel; Oliva-Pascual-Vaca, Jesús; Llabrés-Bennasar, Bartomeu; Oliva-Pascual-Vaca, Ángel

    2017-02-01

    To evaluate the effects of a protocol involving soft tissue techniques and/or neural mobilization techniques in the management of patients with frequent episodic tension-type headache (FETTH) and those with chronic tension-type headache (CTTH). Randomized, double-blind, placebo-controlled before and after trial. Rehabilitation area of the local hospital and a private physiotherapy center. Patients (N=97; 78 women, 19 men) diagnosed with FETTH or CTTH were randomly assigned to groups A, B, C, or D. (A) Placebo superficial massage; (B) soft tissue techniques; (C) neural mobilization techniques; (D) a combination of soft tissue and neural mobilization techniques. The pressure pain threshold (PPT) in the temporal muscles (points 1 and 2) and supraorbital region (point 3), the frequency and maximal intensity of pain crisis, and the score in the Headache Impact Test-6 (HIT-6) were evaluated. All variables were assessed before the intervention, at the end of the intervention, and 15 and 30 days after the intervention. Groups B, C, and D had an increase in PPT and a reduction in frequency, maximal intensity, and HIT-6 values in all time points after the intervention as compared with baseline and group A (P<.001 for all cases). Group D had the highest PPT values and the lowest frequency and HIT-6 values after the intervention. The application of soft tissue and neural mobilization techniques to patients with FETTH or CTTH induces significant changes in PPT, the characteristics of pain crisis, and its effect on activities of daily living as compared with the application of these techniques as isolated interventions. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  1. Dynamic changes in Ezh2 gene occupancy underlie its involvement in neural stem cell self-renewal and differentiation towards oligodendrocytes.

    Directory of Open Access Journals (Sweden)

    Falak Sher

    Full Text Available The polycomb group protein Ezh2 is an epigenetic repressor of transcription originally found to prevent untimely differentiation of pluripotent embryonic stem cells. We previously demonstrated that Ezh2 is also expressed in multipotent neural stem cells (NSCs. We showed that Ezh2 expression is downregulated during NSC differentiation into astrocytes or neurons. However, high levels of Ezh2 remained present in differentiating oligodendrocytes until myelinating. This study aimed to elucidate the target genes of Ezh2 in NSCs and in premyelinating oligodendrocytes (pOLs.We performed chromatin immunoprecipitation followed by high-throughput sequencing to detect the target genes of Ezh2 in NSCs and pOLs. We found 1532 target genes of Ezh2 in NSCs. During NSC differentiation, the occupancy of these genes by Ezh2 was alleviated. However, when the NSCs differentiated into oligodendrocytes, 393 of these genes remained targets of Ezh2. Analysis of the target genes indicated that the repressive activity of Ezh2 in NSCs concerns genes involved in stem cell maintenance, in cell cycle control and in preventing neural differentiation. Among the genes in pOLs that were still repressed by Ezh2 were most prominently those associated with neuronal and astrocytic committed cell lineages. Suppression of Ezh2 activity in NSCs caused loss of stem cell characteristics, blocked their proliferation and ultimately induced apoptosis. Suppression of Ezh2 activity in pOLs resulted in derangement of the oligodendrocytic phenotype, due to re-expression of neuronal and astrocytic genes, and ultimately in apoptosis.Our data indicate that the epigenetic repressor Ezh2 in NSCs is crucial for proliferative activity and maintenance of neural stemness. During differentiation towards oligodendrocytes, Ezh2 repression continues particularly to suppress other neural fate choices. Ezh2 is completely downregulated during differentiation towards neurons and astrocytes allowing transcription

  2. The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field

    DEFF Research Database (Denmark)

    Mølsted, Kirsten; Boers, Maria; Kjaer, Inger

    2010-01-01

    was to measure the cranial base angles in individuals with VCFS and, if possible, to discover the developmental field that may be involved in the condition. The study included 33 patients with VCFS from the Copenhagen Cleft Palate Center, Denmark. The genotype was confirmed by fluorescence in situ hybridization......, hypothyroidism, and posterior brain abnormality), suggest involvement of a specific developmental field....

  3. Method for integrating microelectromechanical devices with electronic circuitry

    Science.gov (United States)

    Barron, Carole C.; Fleming, James G.; Montague, Stephen

    1999-01-01

    A method is disclosed for integrating one or more microelectromechanical (MEM) devices with electronic circuitry on a common substrate. The MEM device can be fabricated within a substrate cavity and encapsulated with a sacrificial material. This allows the MEM device to be annealed and the substrate planarized prior to forming electronic circuitry on the substrate using a series of standard processing steps. After fabrication of the electronic circuitry, the electronic circuitry can be protected by a two-ply protection layer of titanium nitride (TiN) and tungsten (W) during an etch release process whereby the MEM device is released for operation by etching away a portion of a sacrificial material (e.g. silicon dioxide or a silicate glass) that encapsulates the MEM device. The etch release process is preferably performed using a mixture of hydrofluoric acid (HF) and hydrochloric acid (HCI) which reduces the time for releasing the MEM device compared to use of a buffered oxide etchant. After release of the MEM device, the TiN:W protection layer can be removed with a peroxide-based etchant without damaging the electronic circuitry.

  4. The music of your emotions: neural substrates involved in detection of emotional correspondence between auditory and visual music actions.

    Directory of Open Access Journals (Sweden)

    Karin Petrini

    Full Text Available In humans, emotions from music serve important communicative roles. Despite a growing interest in the neural basis of music perception, action and emotion, the majority of previous studies in this area have focused on the auditory aspects of music performances. Here we investigate how the brain processes the emotions elicited by audiovisual music performances. We used event-related functional magnetic resonance imaging, and in Experiment 1 we defined the areas responding to audiovisual (musician's movements with music, visual (musician's movements only, and auditory emotional (music only displays. Subsequently a region of interest analysis was performed to examine if any of the areas detected in Experiment 1 showed greater activation for emotionally mismatching performances (combining the musician's movements with mismatching emotional sound than for emotionally matching music performances (combining the musician's movements with matching emotional sound as presented in Experiment 2 to the same participants. The insula and the left thalamus were found to respond consistently to visual, auditory and audiovisual emotional information and to have increased activation for emotionally mismatching displays in comparison with emotionally matching displays. In contrast, the right thalamus was found to respond to audiovisual emotional displays and to have similar activation for emotionally matching and mismatching displays. These results suggest that the insula and left thalamus have an active role in detecting emotional correspondence between auditory and visual information during music performances, whereas the right thalamus has a different role.

  5. Developmental iodine deficiency and hypothyroidism impair neural development in rat hippocampus: involvement of doublecortin and NCAM-180

    Science.gov (United States)

    2010-01-01

    Background Developmental iodine deficiency results in inadequate thyroid hormone (TH), which damages the hippocampus. Here, we explored the roles of hippocampal doublecortin and neural cell adhesion molecule (NCAM)-180 in developmental iodine deficiency and hypothyroidism. Methods Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil (PTU)-adulterated water (5 ppm or 15 ppm) to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day (PN) 28. Silver-stained neurons and protein levels of doublecortin and NCAM-180 in several hippocampal subregions were assessed on PN14, PN21, PN28, and PN42. Results The results show that nerve fibers in iodine-deficient and 15 ppm PTU-treated rats were injured on PN28 and PN42. Downregulation of doublecortin and upregulation of NCAM-180 were observed in iodine-deficient and 15 ppm PTU-treated rats from PN14 on. These alterations were irreversible by the restoration of serum TH concentrations on PN42. Conclusion Developmental iodine deficiency and hypothyroidism impair the expression of doublecortin and NCAM-180, leading to nerve fiber malfunction and thus impairments in hippocampal development. PMID:20412599

  6. Developmental iodine deficiency and hypothyroidism impair neural development in rat hippocampus: involvement of doublecortin and NCAM-180

    Directory of Open Access Journals (Sweden)

    Zhong Jiapeng

    2010-04-01

    Full Text Available Abstract Background Developmental iodine deficiency results in inadequate thyroid hormone (TH, which damages the hippocampus. Here, we explored the roles of hippocampal doublecortin and neural cell adhesion molecule (NCAM-180 in developmental iodine deficiency and hypothyroidism. Methods Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil (PTU-adulterated water (5 ppm or 15 ppm to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day (PN 28. Silver-stained neurons and protein levels of doublecortin and NCAM-180 in several hippocampal subregions were assessed on PN14, PN21, PN28, and PN42. Results The results show that nerve fibers in iodine-deficient and 15 ppm PTU-treated rats were injured on PN28 and PN42. Downregulation of doublecortin and upregulation of NCAM-180 were observed in iodine-deficient and 15 ppm PTU-treated rats from PN14 on. These alterations were irreversible by the restoration of serum TH concentrations on PN42. Conclusion Developmental iodine deficiency and hypothyroidism impair the expression of doublecortin and NCAM-180, leading to nerve fiber malfunction and thus impairments in hippocampal development.

  7. The music of your emotions: neural substrates involved in detection of emotional correspondence between auditory and visual music actions.

    Science.gov (United States)

    Petrini, Karin; Crabbe, Frances; Sheridan, Carol; Pollick, Frank E

    2011-04-29

    In humans, emotions from music serve important communicative roles. Despite a growing interest in the neural basis of music perception, action and emotion, the majority of previous studies in this area have focused on the auditory aspects of music performances. Here we investigate how the brain processes the emotions elicited by audiovisual music performances. We used event-related functional magnetic resonance imaging, and in Experiment 1 we defined the areas responding to audiovisual (musician's movements with music), visual (musician's movements only), and auditory emotional (music only) displays. Subsequently a region of interest analysis was performed to examine if any of the areas detected in Experiment 1 showed greater activation for emotionally mismatching performances (combining the musician's movements with mismatching emotional sound) than for emotionally matching music performances (combining the musician's movements with matching emotional sound) as presented in Experiment 2 to the same participants. The insula and the left thalamus were found to respond consistently to visual, auditory and audiovisual emotional information and to have increased activation for emotionally mismatching displays in comparison with emotionally matching displays. In contrast, the right thalamus was found to respond to audiovisual emotional displays and to have similar activation for emotionally matching and mismatching displays. These results suggest that the insula and left thalamus have an active role in detecting emotional correspondence between auditory and visual information during music performances, whereas the right thalamus has a different role.

  8. A Physics-driven Neural Networks-based Simulation System (PhyNNeSS) for multimodal interactive virtual environments involving nonlinear deformable objects.

    Science.gov (United States)

    De, Suvranu; Deo, Dhannanjay; Sankaranarayanan, Ganesh; Arikatla, Venkata S

    2011-08-01

    BACKGROUND: While an update rate of 30 Hz is considered adequate for real time graphics, a much higher update rate of about 1 kHz is necessary for haptics. Physics-based modeling of deformable objects, especially when large nonlinear deformations and complex nonlinear material properties are involved, at these very high rates is one of the most challenging tasks in the development of real time simulation systems. While some specialized solutions exist, there is no general solution for arbitrary nonlinearities. METHODS: In this work we present PhyNNeSS - a Physics-driven Neural Networks-based Simulation System - to address this long-standing technical challenge. The first step is an off-line pre-computation step in which a database is generated by applying carefully prescribed displacements to each node of the finite element models of the deformable objects. In the next step, the data is condensed into a set of coefficients describing neurons of a Radial Basis Function network (RBFN). During real-time computation, these neural networks are used to reconstruct the deformation fields as well as the interaction forces. RESULTS: We present realistic simulation examples from interactive surgical simulation with real time force feedback. As an example, we have developed a deformable human stomach model and a Penrose-drain model used in the Fundamentals of Laparoscopic Surgery (FLS) training tool box. CONCLUSIONS: A unique computational modeling system has been developed that is capable of simulating the response of nonlinear deformable objects in real time. The method distinguishes itself from previous efforts in that a systematic physics-based pre-computational step allows training of neural networks which may be used in real time simulations. We show, through careful error analysis, that the scheme is scalable, with the accuracy being controlled by the number of neurons used in the simulation. PhyNNeSS has been integrated into SoFMIS (Software Framework for Multimodal

  9. Nanocantilever based mass sensor integrated with cmos circuitry

    DEFF Research Database (Denmark)

    Davis, Zachary James; Abadal, G.; Campabadal, F.

    2003-01-01

    We have demonstrated the successful integration of a cantilever based mass detector with standard CMOS circuitry. The purpose of the circuitry is to facilitate the readout of the cantilever's deflection in order to measure resonant frequency shifts of the cantilever. The principle and design...... to solve the problem, namely freeze-drying and resist-assisted release. The fabrication results of cantilevers defined by laser and E-beam lithography are shown. Finally, an AFM based characterization setup is presented and the electrical characterization of a laser-defined cantilever fully integrated...

  10. Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5

    Directory of Open Access Journals (Sweden)

    You Ning

    2015-01-01

    Full Text Available Neural stem cells (NSCs harbor the potential to differentiate into neurons, astrocytes, and oligodendrocytes under normal conditions and/or in response to tissue damage. NSCs open a new way of treatment of the injured central nervous system and neurodegenerative disorders. Thus far, few drugs have been developed for controlling NSC functions. Here, the effect as well as mechanism of oleanolic acid (OA, a pentacyclic triterpenoid, on NSC function was investigated. We found OA significantly inhibited neurosphere formation in a dose-dependent manner and achieved a maximum effect at 10 nM. OA also reduced 5-ethynyl-2′-deoxyuridine (EdU incorporation into NSCs, which was indicative of inhibited NSC proliferation. Western blotting analysis revealed the protein levels of neuron-specific marker tubulin-βIII (TuJ1 and Mash1 were increased whilst the astrocyte-specific marker glial fibrillary acidic protein (GFAP decreased. Immunofluorescence analysis showed OA significantly elevated the percentage of TuJ1-positive cells and reduced GFAP-positive cells. Using DNA microarray analysis, 183 genes were differentially regulated by OA. Through transcription factor binding site analyses of the upstream regulatory sequences of these genes, 87 genes were predicted to share a common motif for Nkx-2.5 binding. Finally, small interfering RNA (siRNA methodology was used to silence Nkx-2.5 expression and found silence of Nkx-2.5 alone did not change the expression of TuJ-1 and the percentage of TuJ-1-positive cells. But in combination of OA treatment and silence of Nkx-2.5, most effects of OA on NSCs were abolished. These results indicated that OA is an effective inducer for NSCs differentiation into neurons at least partially by Nkx-2.5-dependent mechanism.

  11. Filtrado digital neuronal difuso: caso MIMO Neural fuzzy digital filtering: multivariate identifier filters involving multiple inputs and multiple outputs (MIMO

    Directory of Open Access Journals (Sweden)

    Medel Juárez José de J.

    2011-05-01

    convergence to observable reference system dynamics. One way of complying with this condition is to use fuzzy logic inference mechanisms which interpret and select the best matrix parameter from a knowledge base. Such selection mechanisms with neural networks can provide a response from the best operational level for each change in state (Shannon, 1948. This paper considers the MIMO digital filter model using neuro fuzzy digital filtering to find an adaptive  parameter matrix which is integrated into the Kalman filter by the transition matrix. The filter uses the neural network as back-propagation into the fuzzy mechanism to do this, interpreting its variables and its respective levels and selecting the best values for automatically adjusting transition matrix values. The Matlab simulation describes the neural fuzzy digital filter giving an approximation of exponential convergence seen in functional error.

     

  12. Dynamic Changes in Ezh2 Gene Occupancy Underlie Its Involvement in Neural Stem Cell Self-Renewal and Differentiation towards Oligodendrocytes

    Science.gov (United States)

    Sher, Falak; Boddeke, Erik; Olah, Marta; Copray, Sjef

    2012-01-01

    Background The polycomb group protein Ezh2 is an epigenetic repressor of transcription originally found to prevent untimely differentiation of pluripotent embryonic stem cells. We previously demonstrated that Ezh2 is also expressed in multipotent neural stem cells (NSCs). We showed that Ezh2 expression is downregulated during NSC differentiation into astrocytes or neurons. However, high levels of Ezh2 remained present in differentiating oligodendrocytes until myelinating. This study aimed to elucidate the target genes of Ezh2 in NSCs and in premyelinating oligodendrocytes (pOLs). Methodology/Principal Findings We performed chromatin immunoprecipitation followed by high-throughput sequencing to detect the target genes of Ezh2 in NSCs and pOLs. We found 1532 target genes of Ezh2 in NSCs. During NSC differentiation, the occupancy of these genes by Ezh2 was alleviated. However, when the NSCs differentiated into oligodendrocytes, 393 of these genes remained targets of Ezh2. Analysis of the target genes indicated that the repressive activity of Ezh2 in NSCs concerns genes involved in stem cell maintenance, in cell cycle control and in preventing neural differentiation. Among the genes in pOLs that were still repressed by Ezh2 were most prominently those associated with neuronal and astrocytic committed cell lineages. Suppression of Ezh2 activity in NSCs caused loss of stem cell characteristics, blocked their proliferation and ultimately induced apoptosis. Suppression of Ezh2 activity in pOLs resulted in derangement of the oligodendrocytic phenotype, due to re-expression of neuronal and astrocytic genes, and ultimately in apoptosis. Conclusions/Significance Our data indicate that the epigenetic repressor Ezh2 in NSCs is crucial for proliferative activity and maintenance of neural stemness. During differentiation towards oligodendrocytes, Ezh2 repression continues particularly to suppress other neural fate choices. Ezh2 is completely downregulated during differentiation

  13. The origin of behavioral bursts in decision-making circuitry.

    Directory of Open Access Journals (Sweden)

    Amanda Sorribes

    2011-06-01

    Full Text Available From ants to humans, the timing of many animal behaviors comes in bursts of activity separated by long periods of inactivity. Recently, mathematical modeling has shown that simple algorithms of priority-driven behavioral choice can result in bursty behavior. To experimentally test this link between decision-making circuitry and bursty dynamics, we have turned to Drosophila melanogaster. We have found that the statistics of intervals between activity periods in endogenous activity-rest switches of wild-type Drosophila are very well described by the Weibull distribution, a common distribution of bursty dynamics in complex systems. The bursty dynamics of wild-type Drosophila walking activity are shown to be determined by this inter-event distribution alone and not by memory effects, thus resembling human dynamics. Further, using mutant flies that disrupt dopaminergic signaling or the mushroom body, circuitry implicated in decision-making, we show that the degree of behavioral burstiness can be modified. These results are thus consistent with the proposed link between decision-making circuitry and bursty dynamics, and highlight the importance of using simple experimental systems to test general theoretical models of behavior. The findings further suggest that analysis of bursts could prove useful for the study and evaluation of decision-making circuitry.

  14. Rugged microelectronic module package supports circuitry on heat sink

    Science.gov (United States)

    Johnson, A. L.

    1966-01-01

    Rugged module package for thin film hybrid microcircuits incorporated a rigid, thermally conductive support structure, which serves as a heat sink, and a lead wire block in which T-shaped electrical connectors are potted. It protects the circuitry from shock and vibration loads, dissipates internal heat, and simplifies electrical connections between adjacent modules.

  15. Reward Circuitry Function in Autism during Face Anticipation and Outcomes

    Science.gov (United States)

    Dichter, Gabriel S.; Richey, J. Anthony; Rittenberg, Alison M.; Sabatino, Antoinette; Bodfish, James W.

    2012-01-01

    The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary…

  16. Development and aging of human spinal cord circuitries

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; Willerslev-Olsen, Maria; Lorentzen, Jakob

    2017-01-01

    development and to what extent they are shaped according to the demands of the body that they control and the environment that the body has to interact with. We also discuss how ageing processes and physiological changes in our body are reflected in adaptations of activity in the spinal cord motor circuitries...

  17. Addiction circuitry in the human brain (*).

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.

    2011-09-27

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.

  18. High throughput analysis reveals dissociable gene expression profiles in two independent neural systems involved in the regulation of social behavior

    Directory of Open Access Journals (Sweden)

    Stevenson Tyler J

    2012-10-01

    Full Text Available Abstract Background Production of contextually appropriate social behaviors involves integrated activity across many brain regions. Many songbird species produce complex vocalizations called ‘songs’ that serve to attract potential mates, defend territories, and/or maintain flock cohesion. There are a series of discrete interconnect brain regions that are essential for the successful production of song. The probability and intensity of singing behavior is influenced by the reproductive state. The objectives of this study were to examine the broad changes in gene expression in brain regions that control song production with a brain region that governs the reproductive state. Results We show using microarray cDNA analysis that two discrete brain systems that are both involved in governing singing behavior show markedly different gene expression profiles. We found that cortical and basal ganglia-like brain regions that control the socio-motor production of song in birds exhibit a categorical switch in gene expression that was dependent on their reproductive state. This pattern is in stark contrast to the pattern of expression observed in a hypothalamic brain region that governs the neuroendocrine control of reproduction. Subsequent gene ontology analysis revealed marked variation in the functional categories of active genes dependent on reproductive state and anatomical localization. HVC, one cortical-like structure, displayed significant gene expression changes associated with microtubule and neurofilament cytoskeleton organization, MAP kinase activity, and steroid hormone receptor complex activity. The transitions observed in the preoptic area, a nucleus that governs the motivation to engage in singing, exhibited variation in functional categories that included thyroid hormone receptor activity, epigenetic and angiogenetic processes. Conclusions These findings highlight the importance of considering the temporal patterns of gene expression

  19. Congenital prosopagnosia: multistage anatomical and functional deficits in face processing circuitry.

    Science.gov (United States)

    Dinkelacker, V; Grüter, M; Klaver, P; Grüter, T; Specht, K; Weis, S; Kennerknecht, I; Elger, C E; Fernandez, G

    2011-05-01

    Face recognition is a primary social skill which depends on a distributed neural network. A pronounced face recognition deficit in the absence of any lesion is seen in congenital prosopagnosia. This study investigating 24 congenital prosopagnosic subjects and 25 control subjects aims at elucidating its neural basis with fMRI and voxel-based morphometry. We found a comprehensive behavioral pattern, an impairment in visual recognition for faces and buildings that spared long-term memory for faces with negative valence. Anatomical analysis revealed diminished gray matter density in the bilateral lingual gyrus, the right middle temporal gyrus, and the dorsolateral prefrontal cortex. In most of these areas, gray matter density correlated with memory success. Decreased functional activation was found in the left fusiform gyrus, a crucial area for face processing, and in the dorsolateral prefrontal cortex, whereas activation of the medial prefrontal cortex was enhanced. Hence, our data lend strength to the hypothesis that congenital prosopagnosia is explained by network dysfunction and suggest that anatomic curtailing of visual processing in the lingual gyrus plays a substantial role. The dysfunctional circuitry further encompasses the fusiform gyrus and the dorsolateral prefrontal cortex, which may contribute to their difficulties in long-term memory for complex visual information. Despite their deficits in face identity recognition, processing of emotion related information is preserved and possibly mediated by the medial prefrontal cortex. Congenital prosopagnosia may, therefore, be a blueprint of differential curtailing in networks of visual cognition.

  20. Imaging conditioned fear circuitry using awake rodent fMRI.

    Directory of Open Access Journals (Sweden)

    Nichola M Brydges

    Full Text Available Functional magnetic resonance imaging (fMRI is a powerful method for exploring emotional and cognitive brain responses in humans. However rodent fMRI has not previously been applied to the analysis of learned behaviour in awake animals, limiting its use as a translational tool. Here we have developed a novel paradigm for studying brain activation in awake rats responding to conditioned stimuli using fMRI. Using this method we show activation of the amygdala and related fear circuitry in response to a fear-conditioned stimulus and demonstrate that the magnitude of fear circuitry activation is increased following early life stress, a rodent model of affective disorders. This technique provides a new translatable method for testing environmental, genetic and pharmacological manipulations on emotional and cognitive processes in awake rodent models.

  1. Using Intrinsic Flavoprotein and NAD(P)H Imaging to Map Functional Circuitry in the Main Olfactory Bulb

    Science.gov (United States)

    Puche, Adam C.; Munger, Steven D.

    2016-01-01

    Neurons exhibit strong coupling of electrochemical and metabolic activity. Increases in intrinsic fluorescence from either oxidized flavoproteins or reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] in the mitochondria have been used as an indicator of neuronal activity for the functional mapping of neural circuits. However, this technique has not been used to investigate the flow of olfactory information within the circuitry of the main olfactory bulb (MOB). We found that intrinsic flavoprotein fluorescence signals induced by electrical stimulation of single glomeruli displayed biphasic responses within both the glomerular (GL) and external plexiform layers (EPL) of the MOB. Pharmacological blockers of mitochondrial activity, voltage-gated Na+ channels, or ionotropic glutamate receptors abolished stimulus-dependent flavoprotein responses. Blockade of GABAA receptors enhanced the amplitude and spatiotemporal spread of the flavoprotein signals, indicating an important role for inhibitory neurotransmission in shaping the spread of neural activity in the MOB. Stimulus-dependent spread of fluorescence across the GL and EPL displayed a spatial distribution consistent with that of individual glomerular microcircuits mapped by neuroanatomic tract tracing. These findings demonstrated the feasibility of intrinsic fluorescence imaging in the olfactory systems and provided a new tool to examine the functional circuitry of the MOB. PMID:27902689

  2. The reciprocal cerebellar circuitry in human hereditary ataxia.

    Science.gov (United States)

    Koeppen, Arnulf H; Ramirez, R Liane; Bjork, Sarah T; Bauer, Peter; Feustel, Paul J

    2013-08-01

    Clinicoanatomic correlation in the spinocerebellar ataxias (SCA) and Friedreich's ataxia (FRDA) is difficult as these diseases differentially affect multiple sites in the central and peripheral nervous systems. A new way to study cerebellar ataxia is the systematic analysis of the "reciprocal cerebellar circuitry" that consists of tightly organized reciprocal connections between Purkinje cells, dentate nuclei (DN), and inferior olivary nuclei (ION). This circuitry is similar to but not identical with the "cerebellar module" in experimental animals. Neurohumoral transmitters operating in the circuitry are both inhibitory (γ-aminobutyric acid in corticonuclear and dentato-olivary fibers) and excitatory (glutamate in olivocerebellar or climbing fibers). Glutamatergic climbing fibers also issue collaterals to the DN. The present study applied five immunohistochemical markers in six types of SCA (1, 2, 3, 6, 7, 17), genetically undefined SCA, FRDA, and FRDA carriers to identify interruptions within the circuitry: calbindin-D28k, neuron-specific enolase, glutamic acid decarboxylase, and vesicular glutamate transporters 1 and 2. Lesions of the cerebellar cortex, DN, and ION were scored according to a guide as 0 (normal), 1 (mild), 2 (moderate), and 3 (severe). Results of each of the five immunohistochemical stains were examined separately for each of the three regions. Combining scores of each anatomical region and each stain yielded a total score as an indicator of pathological severity. Total scores ranged from 16 to 38 in SCA-1 (nine cases); 22 to 39 in SCA-2 (six cases); 9 to 15 in SCA-3 (four cases); and 13 and 25 in SCA-6 (two cases). In single cases of SCA-7 and SCA-17, scores were 16 and 31, respectively. In two genetically undefined SCA, scores were 36 and 37, respectively. In nine cases of FRDA, total scores ranged from 11 to 19. The low scores in SCA-3 and FRDA reflect selective atrophy of the DN. The FRDA carriers did not differ from normal controls. These

  3. dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a non-apoptotic mechanism involving Archipelago and cyclin E.

    Directory of Open Access Journals (Sweden)

    Yingshi Ouyang

    Full Text Available Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53 was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E. Overexpression of Cyc E was able to abrogate dp53's ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago, a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has

  4. Neural correlates of anxiety sensitivity in panic disorder: A functional magnetic resonance imaging study.

    Science.gov (United States)

    Poletti, Sara; Radaelli, Daniele; Cucchi, Michele; Ricci, Liana; Vai, Benedetta; Smeraldi, Enrico; Benedetti, Francesco

    2015-08-30

    Panic disorder has been associated with dysfunctional neuropsychological dimensions, including anxiety sensitivity. Brain-imaging studies of the neural correlates of emotional processing have identified a network of structures that constitute the neural circuitry for emotions. The anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC) and insula, which are part of this network, are also involved in the processing of threat-related stimuli. The aim of the study was to investigate if neural activity in response to emotional stimuli in the cortico-limbic network is associated to anxiety sensitivity in panic disorder. In a sample of 18 outpatients with panic disorder, we studied neural correlates of implicit emotional processing of facial affect expressions with a face-matching paradigm; correlational analyses were performed between brain activations and anxiety sensitivity. The correlational analyses performed showed a positive correlation between anxiety sensitivity and brain activity during emotional processing in regions encompassing the PFC, ACC and insula. Our data seem to confirm that anxiety sensitivity is an important component of panic disorder. Accordingly, the neural underpinnings of anxiety sensitivity could be an interesting focus for treatment and further research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Morphological neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)

    1996-12-31

    The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

  6. Neural correlates of the perception for novel objects.

    Directory of Open Access Journals (Sweden)

    Hao Zhang

    Full Text Available Perception of novel objects is of enormous importance in our lives. People have to perceive or understand novel objects when seeing an original painting, admiring an unconventional construction, and using an inventive device. However, very little is known about neural mechanisms underlying the perception for novel objects. Perception of novel objects relies on the integration of unusual features of novel objects in order to identify what such objects are. In the present study, functional Magnetic Resonance Imaging (MRI was employed to investigate neural correlates of perception of novel objects. The neuroimaging data on participants engaged in novel object viewing versus ordinary object viewing revealed that perception of novel objects involves significant activation in the left precuneus (Brodmann area 7 and the right visual cortex. The results suggest that the left precuneus is associated with the integration of unusual features of novel objects, while the right visual cortex is sensitive to the detection of such features. Our findings highlight the left precuneus as a crucial component of the neural circuitry underlying perception of novel objects.

  7. Testing the connections within face processing circuitry in Capgras delusion with diffusion imaging tractography

    Directory of Open Access Journals (Sweden)

    Maria A. Bobes

    2016-01-01

    Full Text Available Although Capgras delusion (CD patients are capable of recognizing familiar faces, they present a delusional belief that some relatives have been replaced by impostors. CD has been explained as a selective disruption of a pathway processing affective values of familiar faces. To test the integrity of connections within face processing circuitry, diffusion tensor imaging was performed in a CD patient and 10 age-matched controls. Voxel-based morphometry indicated gray matter damage in right frontal areas. Tractography was used to examine two important tracts of the face processing circuitry: the inferior fronto-occipital fasciculus (IFOF and the inferior longitudinal (ILF. The superior longitudinal fasciculus (SLF and commissural tracts were also assessed. CD patient did not differ from controls in the commissural fibers, or the SLF. Right and left ILF, and right IFOF were also equivalent to those of controls. However, the left IFOF was significantly reduced respect to controls, also showing a significant dissociation with the ILF, which represents a selective impairment in the fiber-tract connecting occipital and frontal areas. This suggests a possible involvement of the IFOF in affective processing of faces in typical observers and in covert recognition in some cases with prosopagnosia.

  8. Neural Control of the Lower Urinary Tract

    Science.gov (United States)

    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

  9. Inducing nonlinear dynamic response via piezoelectric circuitry integration

    Science.gov (United States)

    Xu, J.; Tang, J.

    2014-04-01

    Owing to the two-way electro-mechanical coupling characteristics, piezoelectric transducers have been widely used as sensors and actuators in sensing and control applications. In this research, we explore the integration of piezoelectric transducer with the structure, in which the transducer is connected with a Wheatstone bridge based circuitry subjected to chaotic excitation. It is shown that a type of Wheatstone bridge circuit with proper parameters configuration can increase sensitivity in detecting structural anomaly. Such integration has the potential to significantly amplify the response change when the underlying structure is subject to property change. Comprehensive analytical and experimental studies are carried out to demonstrate the concept and validate the performance improvement.

  10. Autonomic neural control of the cardiovascular system in patients with Behçet's disease in the absence of neurological involvement.

    Science.gov (United States)

    Erol, Tansel; Tekin, Abdullah; Tufan, Müge; Altay, Hakan; Tekin, Göknur; Bilgi, Muhammet; Özin, Bülent; Yücel, Eftal; Müderrisoğlu, Haldun

    2012-10-01

    Behçet's disease (BD) is a chronic multi-system disease presenting with recurrent oral and genital ulceration, and relapsing uveitis. Heart rate recovery (HRR) after exercise is a marker of parasympathetic activity. A delayed recovery of systolic blood pressure (SBP) after exercise might reflect sympathetic hyperactivity. The analysis of variations in heart rate has also been used to determine the balance between sympathetic and vagal nerve activities in the heart. Our objective was to determine HRR, the SBP response to exercise and heart rate variability (HRV) in patients with BD in the absence of neurological involvement. The study population consisted of 32 patients with BD and 30 healthy controls who were matched with respect to age, sex, and physical activity. Heart rate recovery was calculated as the difference between heart rate at peak exercise and heart rate at 1, 2, and 3 min of recovery. Blood pressure recovery indexes were determined by dividing the systolic blood pressure at 2 and 3 min in recovery to the systolic blood pressure at peak exercise. In patients with BD, mean HRR at 1 min (HRR1) were not significantly different than that of controls (21 ± 7 vs 20 ± 7 bpm, p = 0.50). Although, resting mean SBP of patients with BD was higher than controls (121 ± 13 vs 115 ± 12 mmHg, p = 0.039), the SBP recovery indices of the patients with BD at 2 and 3 min were similar to those of controls (0.84 ± 0.07 vs 0.84 ± 0.09, p = 0.89 and 0.78 ± 0.09 vs 0.78 ± 0.08, p = 0.93, respectively). Both time domain and frequency domain parameters of patients with BD were similar to that of controls. This study shows that the patients with BD have normal HRR1 and normal SBP response to exercise and normal HRV. These findings might suggest unaltered autonomic neural control of the cardiovascular system in this disorder in the absence of neurological involvement.

  11. Advanced Data Acquisition Systems with Self-Healing Circuitry

    Science.gov (United States)

    Larson, William E.; Ihlefeld, Curtis M.; Medelius, Pedro J.; Delgado, H. (Technical Monitor)

    2001-01-01

    Kennedy Space Center's Spaceport Engineering & Technology Directorate has developed a data acquisition system that will help drive down the cost of ground launch operations. This system automates both the physical measurement set-up function as well as configuration management documentation. The key element of the system is a self-configuring, self-calibrating, signal-conditioning amplifier that automatically adapts to any sensor to which it is connected. This paper will describe the core technology behind this device and the automated data system in which it has been integrated. The paper will also describe the revolutionary enhancements that are planned for this innovative measurement technology. All measurement electronics devices contain circuitry that, if it fails or degrades, requires the unit to be replaced, adding to the cost of operations. Kennedy Space Center is now developing analog circuits that will be able to detect their own failure and dynamically reconfigure their circuitry to restore themselves to normal operation. This technology will have wide ranging application in all electronic devices used in space and ground systems.

  12. Impedance-based damage identification enhancement via tunable piezoelectric circuitry

    Science.gov (United States)

    Kim, Jinki; Wang, K. W.

    2014-03-01

    The piezoelectric impedance-based method for damage detection has been explored extensively for its high sensitivity to small-sized damages with low-cost measurement circuit which enables remote damage monitoring. While the method has good potential, the amount of feasible impedance data is usually much less than the number of required system parameters to accurately identify the damage location/severity via an inverse formulation. This data incompleteness forms a highly underdetermined problem and because of this numerical ill-conditioning, the predicted damage parameters will be significantly influenced by unavoidable measurement noise and the accuracy of the base-line model. In this study, the state of the art of impedance-based damage identification is advanced by incorporating a tunable piezoelectric circuitry with the structure to enrich the impedance measurements. This piezoelectric circuitry introduces additional degrees of freedom to the structure and changes the dynamics of the coupled system. By tuning the inductance value, it is possible to perform various measurements under different system dynamics which reflects the damage effect. Therefore, if performed systematically, notably increased sets of measurement can be obtained, which will improve the inverse problem to be less underdetermined. Clearly, we can expect the accuracy and robustness in damage identification to be significantly enhanced. Numerical case study on localizing damage in a fixed-fixed beam using spectral element method is performed to demonstrate the effectiveness of the new method for structural damage identification.

  13. Phytochemical regulation of Fyn and AMPK signaling circuitry.

    Science.gov (United States)

    Lee, Chan Gyu; Koo, Ja Hyun; Kim, Sang Geon

    2015-12-01

    During the past decades, phytochemical terpenoids, polyphenols, lignans, flavonoids, and alkaloids have been identified as antioxidative and cytoprotective agents. Adenosine monophosphate-activated protein kinase (AMPK) is a kinase that controls redox-state and oxidative stress in the cell, and serves as a key molecule regulating energy metabolism. Many phytochemicals directly or indirectly alter the AMPK pathway in distinct manners, exerting catabolic metabolism. Some of them are considered promising in the treatment of metabolic diseases such as type II diabetes, obesity, and hyperlipidemia. Another important kinase that regulates energy metabolism is Fyn kinase, a member of the Src family kinases that plays a role in various cellular responses such as insulin signaling, cell growth, oxidative stress and apoptosis. Phytochemical inhibition of Fyn leads to AMPK-mediated protection of the cell in association with increased antioxidative capacity and mitochondrial biogenesis. The kinases may work together to form a signaling circuitry for the homeostasis of energy conservation and expenditure, and may serve as targets of phytochemicals. This review is intended as a compilation of recent advancements in the pharmacological research of phytochemicals targeting Fyn and AMPK circuitry, providing information for the prevention and treatment of metabolic diseases and the accompanying tissue injuries.

  14. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Jr., Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bobrek, Miljko [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

    2015-12-01

    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios where human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments due the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is the final report of the activities involving the NEET 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays. We present a detailed functional block diagram of the proposed data acquisition system, the thought process leading to technical decisions, the implemented system, and the tested results from the systems. This system will be capable of monitoring at least three parameters of importance to nuclear reactor monitoring: temperature, radiation level, and pressure.

  15. Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry

    Directory of Open Access Journals (Sweden)

    Daniel Charles Castro

    2015-06-01

    Full Text Available The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc and ventral pallidum (VP, in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact (‘liking’ and motivational incentive salience (‘wanting’ of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating versus intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including ‘liking’ and ‘wanting’ for food rewards.

  16. Category-Specific Neural Oscillations Predict Recall Organization During Memory Search

    Science.gov (United States)

    Morton, Neal W.; Kahana, Michael J.; Rosenberg, Emily A.; Baltuch, Gordon H.; Litt, Brian; Sharan, Ashwini D.; Sperling, Michael R.; Polyn, Sean M.

    2013-01-01

    Retrieved-context models of human memory propose that as material is studied, retrieval cues are constructed that allow one to target particular aspects of past experience. We examined the neural predictions of these models by using electrocorticographic/depth recordings and scalp electroencephalography (EEG) to characterize category-specific oscillatory activity, while participants studied and recalled items from distinct, neurally discriminable categories. During study, these category-specific patterns predict whether a studied item will be recalled. In the scalp EEG experiment, category-specific activity during study also predicts whether a given item will be recalled adjacent to other same-category items, consistent with the proposal that a category-specific retrieval cue is used to guide memory search. Retrieved-context models suggest that integrative neural circuitry is involved in the construction and maintenance of the retrieval cue. Consistent with this hypothesis, we observe category-specific patterns that rise in strength as multiple same-category items are studied sequentially, and find that individual differences in this category-specific neural integration during study predict the degree to which a participant will use category information to organize memory search. Finally, we track the deployment of this retrieval cue during memory search: Category-specific patterns are stronger when participants organize their responses according to the category of the studied material. PMID:22875859

  17. Neural Emotion Regulation Circuitry Underlying Anxiolytic Effects of Perceived Control Over Pain

    OpenAIRE

    Salomons, Tim V.; Nusslock, Robin; Detloff, Allison; Johnstone, Tom; Davidson, Richard J.

    2015-01-01

    Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within subjects-designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neu...

  18. Neural Circuitry that Evokes Escape Behavior upon Activation of Nociceptive Sensory Neurons in Drosophila Larvae.

    Science.gov (United States)

    Yoshino, Jiro; Morikawa, Rei K; Hasegawa, Eri; Emoto, Kazuo

    2017-08-21

    Noxious stimuli trigger a stereotyped escape response in animals. In Drosophila larvae, class IV dendrite arborization (C4 da) sensory neurons in the peripheral nervous system are responsible for perception of multiple nociceptive modalities, including noxious heat and harsh mechanical stimulation, through distinct receptors [1-9]. Silencing or ablation of C4 da neurons largely eliminates larval responses to noxious stimuli [10-12], whereas optogenetic activation of C4 da neurons is sufficient to provoke corkscrew-like rolling behavior similar to what is observed when larvae receive noxious stimuli, such as high temperature or harsh mechanical stimulation [10-12]. The receptors and the regulatory mechanisms for C4 da activation in response to a variety of noxious stimuli have been well studied [13-23], yet how C4 da activation triggers the escape behavior in the circuit level is still incompletely understood. Here we identify segmentally arrayed local interneurons (medial clusters of C4 da second-order interneurons [mCSIs]) in the ventral nerve cord that are necessary and sufficient to trigger rolling behavior. GFP reconstitution across synaptic partners (GRASP) analysis indicates that C4 da axons form synapses with mCSI dendrites. Optogenetic activation of mCSIs induces the rolling behavior, whereas silencing mCSIs reduces the probability of rolling behavior upon C4 da activation. Further anatomical and functional studies suggest that the C4 da-mCSI nociceptive circuit evokes rolling behavior at least in part through segmental nerve a (SNa) motor neurons. Our findings thus uncover a local circuit that promotes escape behavior upon noxious stimuli in Drosophila larvae and provide mechanistic insights into how noxious stimuli are transduced into the stereotyped escape behavior in the circuit level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. TQUID Magnetometer and Artificial Neural Circuitry Based on a Topological Kondo Insulator

    Science.gov (United States)

    2016-05-01

    samples are leached out in sodium hydroxide solution. The surfaces of these crystals were carefully etched using an equal mixture of hydrochloric acid...person or corporation; or convey any rights or permission to manufacture , use, or sell any patented invention that may relate to them. This report is the...detail. Crystals are grown using the aluminum flux method and selected based on size with extra aluminum etched off with hydrochloric acid. Two

  20. Role of Autism Susceptibility Gene, CNTNAP2, in Neural Circuitry for Vocal Communication

    Science.gov (United States)

    2013-10-01

    Iyama- Kurtycz, C. M., Hartley, S. L., . . . Shriberg, L. D. (2012). Phenotype of FOXP2 haploinsufficiency in a mother and son. American Journal of...2006). Speech, prosody, and voice characteristics of a mother and daughter with a 7;13 translocation affecting FOXP2. Journal of Speech...noninnate vocal output. Along the vocal tract, these include the larynx, pharynx, tongue , teeth, and lips, as well as the muscles of respiration

  1. Stretchable biocompatible electronics by embedding electrical circuitry in biocompatible elastomers.

    Science.gov (United States)

    Jahanshahi, Amir; Salvo, Pietro; Vanfleteren, Jan

    2012-01-01

    Stretchable and curvilinear electronics has been used recently for the fabrication of micro systems interacting with the human body. The applications range from different kinds of implantable sensors inside the body to conformable electrodes and artificial skins. One of the key parameters in biocompatible stretchable electronics is the fabrication of reliable electrical interconnects. Although very recent literature has reported on the reliability of stretchable interconnects by cyclic loading, work still needs to be done on the integration of electrical circuitry composed of rigid components and stretchable interconnects in a biological environment. In this work, the feasibility of a developed technology to fabricate simple electrical circuits with meander shaped stretchable interconnects is presented. Stretchable interconnects are 200 nm thin Au layer supported with polyimide (PI). A stretchable array of light emitting diodes (LEDs) is embedded in biocompatible elastomer using this technology platform and it features a 50% total elongation.

  2. Serotonin: a regulator of neuronal morphology and circuitry

    Science.gov (United States)

    Daubert, Elizabeth A.; Condron, Barry G.

    2010-01-01

    Serotonin is an important neuromodulator associated with a wide range of physiological effects in the central nervous system. The exact mechanisms for how serotonin influences brain development are not well understood, although studies in invertebrate and vertebrate model organisms are beginning to unravel a regulatory role for serotonin in neuronal morphology and circuit formation. Recent data suggests a developmental window during which altered serotonin levels permanently impact circuitry, however, the temporal constraints and molecular mechanisms responsible are still under investigation. Growing evidence suggests that alterations in early serotonin signaling contribute to a number of neurodevelopmental and neuropsychiatric disorders. Thus, understanding how altered serotonin signaling affects neuronal morphology and plasticity, and ultimately animal physiology and pathophysiology, will be of great significance. PMID:20561690

  3. Corticostriatal circuitry in regulating diseases characterized by intrusive thinking.

    Science.gov (United States)

    Kalivas, Benjamin C; Kalivas, Peter W

    2016-03-01

    Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.

  4. Focusing on optic tectum circuitry through the lens of genetics

    Directory of Open Access Journals (Sweden)

    Nevin Linda M

    2010-09-01

    Full Text Available Abstract The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.

  5. Integrated circuit electrometer and sweep circuitry for an atmospheric probe

    Science.gov (United States)

    Zimmerman, L. E.

    1971-01-01

    The design of electrometer circuitry using an integrated circuit operational amplifier with a MOSFET input is described. Input protection against static voltages is provided by a dual ultra low leakage diode or a neon lamp. Factors affecting frequency response leakage resistance, and current stability are discussed, and methods are suggested for increasing response speed and for eliminating leakage resistance and current instabilities. Based on the above, two practical circuits, one having a linear response and the other a logarithmic response, were designed and evaluated experimentally. The design of a sweep circuit to implement mobility measurements using atmospheric probes is presented. A triangular voltage waveform is generated and shaped to contain a step in voltage from zero volts in both positive and negative directions.

  6. Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naïve Adolescent Depression.

    Directory of Open Access Journals (Sweden)

    Haiyang Geng

    Full Text Available Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD. This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure.Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC. Fractional anisotropy (FA values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC region showing significant differences between the two groups was identified.Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group.First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

  7. Dynamic Changes in Ezh2 Gene Occupancy Underlie Its Involvement in Neural Stem Cell Self-Renewal and Differentiation towards Oligodendrocytes

    NARCIS (Netherlands)

    Sher, Falak; Boddeke, Erik; Olah, Marta; Copray, Sjef

    2012-01-01

    Background: The polycomb group protein Ezh2 is an epigenetic repressor of transcription originally found to prevent untimely differentiation of pluripotent embryonic stem cells. We previously demonstrated that Ezh2 is also expressed in multipotent neural stem cells (NSCs). We showed that Ezh2

  8. The neural crest and neural crest cells: discovery and significance ...

    Indian Academy of Sciences (India)

    In this paper I provide a brief overview of the major phases of investigation into the neural crest and the major players involved, discuss how the origin of the neural crest relates to the origin of the nervous system in vertebrate embryos, discuss the impact on the germ-layer theory of the discovery of the neural crest and of ...

  9. Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity

    Science.gov (United States)

    Gee, Dylan G.

    2016-01-01

    Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…

  10. 76 FR 79215 - Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same...

    Science.gov (United States)

    2011-12-21

    ... COMMISSION Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same... importation of certain semiconductor chips with DRAM circuitry, and modules and products containing same by... containing same that infringe one or more of claims 1-6, 8-11, and 15- 18 of the `689 patent; claims 1-16 and...

  11. Stitching Codeable Circuits: High School Students' Learning about Circuitry and Coding with Electronic Textiles

    Science.gov (United States)

    Litts, Breanne K.; Kafai, Yasmin B.; Lui, Debora A.; Walker, Justice T.; Widman, Sari A.

    2017-01-01

    Learning about circuitry by connecting a battery, light bulb, and wires is a common activity in many science classrooms. In this paper, we expand students' learning about circuitry with electronic textiles, which use conductive thread instead of wires and sewable LEDs instead of lightbulbs, by integrating programming sensor inputs and light…

  12. Mapping the Brain’s Metaphor Circuitry:Is Abstract Thought Metaphorical Thought?

    Directory of Open Access Journals (Sweden)

    George eLakoff

    2014-12-01

    Full Text Available An overview of the basics of metaphorical thought and language from the perspective of Neurocognition, the integrated interdisciplinary study of how conceptual thought and language work in the brain. The paper outlines a theory of metaphor circuitry and discusses how everyday reason makes use of embodied metaphor circuitry.

  13. Neural bases of congenital amusia in tonal language speakers.

    Science.gov (United States)

    Zhang, Caicai; Peng, Gang; Shao, Jing; Wang, William S-Y

    2017-03-01

    Congenital amusia is a lifelong neurodevelopmental disorder of fine-grained pitch processing. In this fMRI study, we examined the neural bases of congenial amusia in speakers of a tonal language - Cantonese. Previous studies on non-tonal language speakers suggest that the neural deficits of congenital amusia lie in the music-selective neural circuitry in the right inferior frontal gyrus (IFG). However, it is unclear whether this finding can generalize to congenital amusics in tonal languages. Tonal language experience has been reported to shape the neural processing of pitch, which raises the question of how tonal language experience affects the neural bases of congenital amusia. To investigate this question, we examined the neural circuitries sub-serving the processing of relative pitch interval in pitch-matched Cantonese level tone and musical stimuli in 11 Cantonese-speaking amusics and 11 musically intact controls. Cantonese-speaking amusics exhibited abnormal brain activities in a widely distributed neural network during the processing of lexical tone and musical stimuli. Whereas the controls exhibited significant activation in the right superior temporal gyrus (STG) in the lexical tone condition and in the cerebellum regardless of the lexical tone and music conditions, no activation was found in the amusics in those regions, which likely reflects a dysfunctional neural mechanism of relative pitch processing in the amusics. Furthermore, the amusics showed abnormally strong activation of the right middle frontal gyrus and precuneus when the pitch stimuli were repeated, which presumably reflect deficits of attending to repeated pitch stimuli or encoding them into working memory. No significant group difference was found in the right IFG in either the whole-brain analysis or region-of-interest analysis. These findings imply that the neural deficits in tonal language speakers might differ from those in non-tonal language speakers, and overlap partly with the

  14. Acute Stress Influences Neural Circuits of Reward Processing

    Directory of Open Access Journals (Sweden)

    Anthony John Porcelli

    2012-11-01

    Full Text Available People often make decisions under aversive conditions such as acute stress. Yet, less is known about the process in which acute stress can influence decision-making. A growing body of research has established that reward-related information associated with the outcomes of decisions exerts a powerful influence over the choices people make and that an extensive network of brain regions, prominently featuring the striatum, is involved in the processing of this reward-related information. Thus, an important step in research on the nature of acute stress’ influence over decision-making is to examine how it may modulate responses to rewards and punishments within reward-processing neural circuitry. In the current experiment, we employed a simple reward processing paradigm – where participants received monetary rewards and punishments – known to evoke robust striatal responses. Immediately prior to performing each of two task runs, participants were exposed to acute stress (i.e., cold pressor or a no stress control procedure in a between-subjects fashion. No stress group participants exhibited a pattern of activity within the dorsal striatum and orbitofrontal cortex consistent with past research on outcome processing – specifically, differential responses for monetary rewards over punishments. In contrast, acute stress group participants’ dorsal striatum and orbitofrontal cortex demonstrated decreased sensitivity to monetary outcomes and a lack of differential activity. These findings provide insight into how neural circuits may process rewards and punishments associated with simple decisions under acutely stressful conditions.

  15. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model

    DEFF Research Database (Denmark)

    Tønnesen, Jan; Parish, Clare L; Sørensen, Andreas T

    2011-01-01

    Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral...

  16. Neural plasticity across the lifespan.

    Science.gov (United States)

    Power, Jonathan D; Schlaggar, Bradley L

    2017-01-01

    An essential feature of the brain is its capacity to change. Neuroscientists use the term 'plasticity' to describe the malleability of neuronal connectivity and circuitry. How does plasticity work? A review of current data suggests that plasticity encompasses many distinct phenomena, some of which operate across most or all of the lifespan, and others that operate exclusively in early development. This essay surveys some of the key concepts related to neural plasticity, beginning with how current patterns of neural activity (e.g., as you read this essay) come to impact future patterns of activity (e.g., your memory of this essay), and then extending this framework backward into more development-specific mechanisms of plasticity. WIREs Dev Biol 2017, 6:e216. doi: 10.1002/wdev.216 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  17. Response of neural reward regions to food cues in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Cascio Carissa J

    2012-05-01

    Full Text Available Abstract Background One hypothesis for the social deficits that characterize autism spectrum disorders (ASD is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. Method We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD signal in response to the food images Results We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. Conclusion These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD.

  18. The banana code – Natural blend processing in the olfactory circuitry of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Marco eSchubert

    2014-02-01

    Full Text Available Odor information is predominantly perceived as complex odor blends. For Drosophila melanogaster one of the most attractive blends is emitted by an over-ripe banana. To analyze how the fly’s olfactory system processes natural blends we combined the experimental advantages of gas chromatography and functional imaging (GC-I. In this way, natural banana compounds were presented successively to the fly antenna in close to natural occurring concentrations. This technique allowed us to identify the active odor components, use these compounds as stimuli and measure odor-induced Ca2+ signals in input and output neurons of the Drosophila antennal lobe (AL, the first olfactory neuropil. We demonstrate that mixture interactions of a natural blend are very rare and occur only at the AL output level resulting in a surprisingly linear blend representation. However, the information regarding single components is strongly modulated by the olfactory circuitry within the AL leading to a higher similarity between the representation of individual components and the banana blend. This observed modulation might tune the olfactory system in a way to distinctively categorize odor components and improve the detection of suitable food sources. Functional GC-I thus enables analysis of virtually any unknown natural odorant blend and its components in their relative occurring concentrations and allows characterization of neuronal responses of complete neural assemblies. This technique can be seen as a valuable complementary method to classical GC/electrophysiology techniques, and will be a highly useful tool in future investigations of insect-insect and insect-plant chemical interactions.

  19. Bilingualism yields language-specific plasticity in left hemisphere's circuitry for learning to read in young children.

    Science.gov (United States)

    Jasińska, K K; Berens, M S; Kovelman, I; Petitto, L A

    2017-04-01

    How does bilingual exposure impact children's neural circuitry for learning to read? Theories of bilingualism suggests that exposure to two languages may yield a functional and neuroanatomical adaptation to support the learning of two languages (Klein et al., 2014). To test the hypothesis that this neural adaptation may vary as a function of structural and orthographic characteristics of bilinguals' two languages, we compared Spanish-English and French-English bilingual children, and English monolingual children, using functional Near Infrared Spectroscopy neuroimaging (fNIRS, ages 6-10, N =26). Spanish offers consistent sound-to-print correspondences ("phonologically transparent" or "shallow"); such correspondences are more opaque in French and even more opaque in English (which has both transparent and "phonologically opaque" or "deep" correspondences). Consistent with our hypothesis, both French- and Spanish-English bilinguals showed hyperactivation in left posterior temporal regions associated with direct sound-to-print phonological analyses and hypoactivation in left frontal regions associated with assembled phonology analyses. Spanish, but not French, bilinguals showed a similar effect when reading Irregular words. The findings inform theories of bilingual and cross-linguistic literacy acquisition by suggesting that structural characteristics of bilinguals' two languages and their orthographies have a significant impact on children's neuro-cognitive architecture for learning to read. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

    KAUST Repository

    Schmeier, Sebastian

    2009-12-10

    Background: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee Bio

  1. Optogenetic deconstruction of sleep-wake circuitry in the brain

    Directory of Open Access Journals (Sweden)

    Antoine Adamantidis

    2010-01-01

    Full Text Available How does the brain regulate the sleep-wake cycle? What are the temporal codes of sleep- and wake-promoting neural circuits? How do these circuits interact with each other across the light/dark cycle? Over the past few decades, many studies from a variety of disciplines have made substantial progress in answering these fundamental questions. For example, neurobiologists have identified multiple, redundant wake-promoting circuits in the brainstem, hypothalamus, and basal forebrain. Sleep-promoting circuits have been found in the preoptic area and hypothalamus. One of the greatest challenges in recent years has been to selectively record and manipulate these sleep-wake centers in vivo with high spatial and temporal resolution. Recent developments in microbial opsin-based neuromodulation tools, collectively referred to as “optogenetics,” have provided a novel method to demonstrate causal links between neural activity and specific behaviors. Here, we propose to use optogenetics as a fundamental tool to probe the necessity, sufficiency, and connectivity of defined neural circuits in the regulation of sleep and wakefulness.

  2. Plasticity in the neural coding of auditory space in the mammalian brain

    Science.gov (United States)

    King, Andrew J.; Parsons, Carl H.; Moore, David R.

    2000-10-01

    Sound localization relies on the neural processing of monaural and binaural spatial cues that arise from the way sounds interact with the head and external ears. Neurophysiological studies of animals raised with abnormal sensory inputs show that the map of auditory space in the superior colliculus is shaped during development by both auditory and visual experience. An example of this plasticity is provided by monaural occlusion during infancy, which leads to compensatory changes in auditory spatial tuning that tend to preserve the alignment between the neural representations of visual and auditory space. Adaptive changes also take place in sound localization behavior, as demonstrated by the fact that ferrets raised and tested with one ear plugged learn to localize as accurately as control animals. In both cases, these adjustments may involve greater use of monaural spectral cues provided by the other ear. Although plasticity in the auditory space map seems to be restricted to development, adult ferrets show some recovery of sound localization behavior after long-term monaural occlusion. The capacity for behavioral adaptation is, however, task dependent, because auditory spatial acuity and binaural unmasking (a measure of the spatial contribution to the "cocktail party effect") are permanently impaired by chronically plugging one ear, both in infancy but especially in adulthood. Experience-induced plasticity allows the neural circuitry underlying sound localization to be customized to individual characteristics, such as the size and shape of the head and ears, and to compensate for natural conductive hearing losses, including those associated with middle ear disease in infancy.

  3. Circuitry linking the Csr and stringent response global regulatory systems.

    Science.gov (United States)

    Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

    2011-06-01

    CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

  4. Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease: a randomized clinical trial.

    Science.gov (United States)

    King, L A; Peterson, D S; Mancini, M; Carlson-Kuhta, P; Fling, B W; Smulders, K; Nutt, J G; Dale, M; Carter, J; Winters-Stone, K M; Horak, F B

    2015-10-24

    There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. This trial is registered at clinical trials.gov (NCT02231073).

  5. The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling.

    Science.gov (United States)

    Hayashi, Hisamitsu; Edin, Fredrik; Li, Hao; Liu, Wei; Rask-Andersen, Helge

    2016-12-01

    Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca 2+ signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca 2+ channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca 2+ channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca 2+ signaling. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Neural progenitor cell proliferation in the hypothalamus is involved in acquired heat tolerance in long-term heat-acclimated rats.

    Science.gov (United States)

    Matsuzaki, Kentaro; Katakura, Masanori; Sugimoto, Naotoshi; Hara, Toshiko; Hashimoto, Michio; Shido, Osamu

    2017-01-01

    Constant exposure to moderate heat facilitates progenitor cell proliferation and neuronal differentiation in the hypothalamus of heat-acclimated (HA) rats. In this study, we investigated neural phenotype and responsiveness to heat in HA rats' hypothalamic newborn cells. Additionally, the effect of hypothalamic neurogenesis on heat acclimation in rats was evaluated. Male Wistar rats (5 weeks old) were housed at an ambient temperature (Ta) of 32°C for 6 days (STHA) or 40 days (LTHA), while control (CN) rats were kept at a Ta of 24°C for 6 days (STCN) or 40 days (LTCN). Bromodeoxyuridine (BrdU) was intraperitoneally injected daily for five consecutive days (50 mg/kg/day) after commencing heat exposure. The number of hypothalamic BrdU-immunopositive (BrdU+) cells in STHA and LTHA rats was determined immunohistochemically in brain samples and found to be significantly greater than those in respective CN groups. In LTHA rats, approximately 32.6% of BrdU+ cells in the preoptic area (POA) of the anterior hypothalamus were stained by GAD67, a GABAergic neuron marker, and 15.2% of BrdU+ cells were stained by the glutamate transporter, a glutamatergic neuron marker. In addition, 63.2% of BrdU+ cells in the POA were immunolabeled with c-Fos. Intracerebral administration of the mitosis inhibitor, cytosine arabinoside (AraC), interfered with the proliferation of neural progenitor cells and acquired heat tolerance in LTHA rats, whereas the selected ambient temperature was not changed. These results demonstrate that heat exposure generates heat responsive neurons in the POA, suggesting a pivotal role in autonomic thermoregulation in long-term heat-acclimated rats.

  7. Apparatus, system and method for providing cryptographic key information with physically unclonable function circuitry

    Science.gov (United States)

    Areno, Matthew

    2015-12-08

    Techniques and mechanisms for providing a value from physically unclonable function (PUF) circuitry for a cryptographic operation of a security module. In an embodiment, a cryptographic engine receives a value from PUF circuitry and based on the value, outputs a result of a cryptographic operation to a bus of the security module. The bus couples the cryptographic engine to control logic or interface logic of the security module. In another embodiment, the value is provided to the cryptographic engine from the PUF circuitry via a signal line which is distinct from the bus, where any exchange of the value by either of the cryptographic engine and the PUF circuitry is for communication of the first value independent of the bus.

  8. Neural correlate of human reciprocity in social interactions

    Directory of Open Access Journals (Sweden)

    Shiro eSakaiya

    2013-12-01

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

  9. Neural correlate of human reciprocity in social interactions.

    Science.gov (United States)

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

    2013-01-01

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

  10. Degenerate coding in neural systems.

    Science.gov (United States)

    Leonardo, Anthony

    2005-11-01

    When the dimensionality of a neural circuit is substantially larger than the dimensionality of the variable it encodes, many different degenerate network states can produce the same output. In this review I will discuss three different neural systems that are linked by this theme. The pyloric network of the lobster, the song control system of the zebra finch, and the odor encoding system of the locust, while different in design, all contain degeneracies between their internal parameters and the outputs they encode. Indeed, although the dynamics of song generation and odor identification are quite different, computationally, odor recognition can be thought of as running the song generation circuitry backwards. In both of these systems, degeneracy plays a vital role in mapping a sparse neural representation devoid of correlations onto external stimuli (odors or song structure) that are strongly correlated. I argue that degeneracy between input and output states is an inherent feature of many neural systems, which can be exploited as a fault-tolerant method of reliably learning, generating, and discriminating closely related patterns.

  11. Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism.

    Science.gov (United States)

    Gan, Zhenji; Rumsey, John; Hazen, Bethany C; Lai, Ling; Leone, Teresa C; Vega, Rick B; Xie, Hui; Conley, Kevin E; Auwerx, Johan; Smith, Steven R; Olson, Eric N; Kralli, Anastasia; Kelly, Daniel P

    2013-06-01

    The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgenic mice. In contrast, muscle-specific transgenic overexpression of the related nuclear receptor, PPARα, results in reduced capacity for endurance exercise. We took advantage of the divergent actions of PPARβ/δ and PPARα to explore the downstream regulatory circuitry that orchestrates the programs linking muscle fiber type with energy metabolism. Our results indicate that, in addition to the well-established role in transcriptional control of muscle metabolic genes, PPARβ/δ and PPARα participate in programs that exert opposing actions upon the type I fiber program through a distinct muscle microRNA (miRNA) network, dependent on the actions of another nuclear receptor, estrogen-related receptor γ (ERRγ). Gain-of-function and loss-of-function strategies in mice, together with assessment of muscle biopsies from humans, demonstrated that type I muscle fiber proportion is increased via the stimulatory actions of ERRγ on the expression of miR-499 and miR-208b. This nuclear receptor/miRNA regulatory circuit shows promise for the identification of therapeutic targets aimed at maintaining muscle fitness in a variety of chronic disease states, such as obesity, skeletal myopathies, and heart failure.

  12. Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Russ

    2013-09-01

    Full Text Available During perinatal development, corticospinal tract (CST projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65. In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of descending spinal pathways, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.

  13. Closed circuitry operation influence on microbial electrofermentation: Proton/electron effluxes on electro-fuels productivity.

    Science.gov (United States)

    Nikhil, G N; Venkata Subhash, G; Yeruva, Dileep Kumar; Venkata Mohan, S

    2015-11-01

    A novel biocatalyzed electrofermentor (BEF) was designed which uncovers the intricate role of biocatalyst involved in cogeneration of electro-fuels (hydrogen and electricity). The specific role of external resistance (Rext, electrical load) on the performance of BEF was evaluated. Four BEFs were operated separately with different resistances (25, 50, 100 and 200 Ω) at an organic load of 5 g/L. Among the tested conditions, external resistance (R3) with 100 Ω revealed maximum power and cumulative H2 production (148 mW and 450 mL, respectively). The competence of closed circuitry comparatively excelled because it facilitates congenial ambiance for the enriched EAB (electroactive bacteria) resulting high rate of metabolic activity that paves way for higher substrate degradation and electro-fuel productivity. Probing of electron kinetics was studied using voltammetric analyses wherein electron transfer by redox proteins was noticed. The designed BEF is found to be sustainable system for harnessing renewable energy through wastewater treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Optogenetic manipulation of neural circuits in awake marmosets.

    Science.gov (United States)

    MacDougall, Matthew; Nummela, Samuel U; Coop, Shanna; Disney, Anita; Mitchell, Jude F; Miller, Cory T

    2016-09-01

    Optogenetics has revolutionized the study of functional neuronal circuitry (Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Nat Neurosci 8: 1263-1268, 2005; Deisseroth K. Nat Methods 8: 26-29, 2011). Although these techniques have been most successfully implemented in rodent models, they have the potential to be similarly impactful in studies of nonhuman primate brains. Common marmosets (Callithrix jacchus) have recently emerged as a candidate primate model for gene editing, providing a potentially powerful model for studies of neural circuitry and disease in primates. The application of viral transduction methods in marmosets for identifying and manipulating neuronal circuitry is a crucial step in developing this species for neuroscience research. In the present study we developed a novel, chronic method to successfully induce rapid photostimulation in individual cortical neurons transduced by adeno-associated virus to express channelrhodopsin (ChR2) in awake marmosets. We found that large proportions of neurons could be effectively photoactivated following viral transduction and that this procedure could be repeated for several months. These data suggest that techniques for viral transduction and optical manipulation of neuronal populations are suitable for marmosets and can be combined with existing behavioral preparations in the species to elucidate the functional neural circuitry underlying perceptual and cognitive processes. Copyright © 2016 the American Physiological Society.

  15. Own-gender imitation activates the brain's reward circuitry.

    Science.gov (United States)

    Losin, Elizabeth A Reynolds; Iacoboni, Macro; Martin, Alia; Dapretto, Mirella

    2012-10-01

    Imitation is an important component of human social learning throughout life. Theoretical models and empirical data from anthropology and psychology suggest that people tend to imitate self-similar individuals, and that such imitation biases increase the adaptive value (e.g., self-relevance) of learned information. It is unclear, however, what neural mechanisms underlie people's tendency to imitate those similar to themselves. We focused on the own-gender imitation bias, a pervasive bias thought to be important for gender identity development. While undergoing fMRI, participants imitated own- and other-gender actors performing novel, meaningless hand signs; as control conditions, they also simply observed such actions and viewed still portraits of the same actors. Only the ventral and dorsal striatum, orbitofrontal cortex and amygdala were more active when imitating own- compared to other-gender individuals. A Bayesian analysis of the BrainMap neuroimaging database demonstrated that the striatal region preferentially activated by own-gender imitation is selectively activated by classical reward tasks in the literature. Taken together, these findings reveal a neurobiological mechanism associated with the own-gender imitation bias and demonstrate a novel role of reward-processing neural structures in social behavior.

  16. Neural systems underlying aversive conditioning in humans with primary and secondary reinforcers

    Directory of Open Access Journals (Sweden)

    Mauricio R Delgado

    2011-05-01

    Full Text Available Money is a secondary reinforcer commonly used across a range of disciplines in experimental paradigms investigating reward learning and decision-making. The effectiveness of monetary reinforcers during aversive learning and its neural basis, however, remains a topic of debate. Specifically, it is unclear if the initial acquisition of aversive representations of monetary losses depends on similar neural systems as more traditional aversive conditioning that involves primary reinforcers. This study contrasts the efficacy of a biologically defined primary reinforcer (shock and a socially defined secondary reinforcer (money during aversive learning and its associated neural circuitry. During a two-part experiment, participants first played a gambling game where wins and losses were based on performance to gain an experimental bank. Participants were then exposed to two separate aversive conditioning sessions. In one session, a primary reinforcer (mild shock served as an unconditioned stimulus (US and was paired with one of two colored squares, the conditioned stimuli (CS+ and CS-, respectively. In another session, a secondary reinforcer (loss of money served as the US and was paired with one of two different CS. Skin conductance responses were greater for CS+ compared to CS- trials irrespective of type of reinforcer. Neuroimaging results revealed that the striatum, a region typically linked with reward-related processing, was found to be involved in the acquisition of aversive conditioned response irrespective of reinforcer type. In contrast, the amygdala was involved during aversive conditioning with primary reinforcers, as suggested by both an exploratory fMRI analysis and a follow-up case study with a patient with bilateral amygdala damage. Taken together, these results suggest that learning about potential monetary losses may depend on reinforcement learning related systems, rather than on typical structures involved in more biologically based

  17. Visual motion imagery neurofeedback based on the hMT+/V5 complex: evidence for a feedback-specific neural circuit involving neocortical and cerebellar regions

    Science.gov (United States)

    Banca, Paula; Sousa, Teresa; Catarina Duarte, Isabel; Castelo-Branco, Miguel

    2015-12-01

    Objective. Current approaches in neurofeedback/brain-computer interface research often focus on identifying, on a subject-by-subject basis, the neural regions that are best suited for self-driven modulation. It is known that the hMT+/V5 complex, an early visual cortical region, is recruited during explicit and implicit motion imagery, in addition to real motion perception. This study tests the feasibility of training healthy volunteers to regulate the level of activation in their hMT+/V5 complex using real-time fMRI neurofeedback and visual motion imagery strategies. Approach. We functionally localized the hMT+/V5 complex to further use as a target region for neurofeedback. An uniform strategy based on motion imagery was used to guide subjects to neuromodulate hMT+/V5. Main results. We found that 15/20 participants achieved successful neurofeedback. This modulation led to the recruitment of a specific network as further assessed by psychophysiological interaction analysis. This specific circuit, including hMT+/V5, putative V6 and medial cerebellum was activated for successful neurofeedback runs. The putamen and anterior insula were recruited for both successful and non-successful runs. Significance. Our findings indicate that hMT+/V5 is a region that can be modulated by focused imagery and that a specific cortico-cerebellar circuit is recruited during visual motion imagery leading to successful neurofeedback. These findings contribute to the debate on the relative potential of extrinsic (sensory) versus intrinsic (default-mode) brain regions in the clinical application of neurofeedback paradigms. This novel circuit might be a good target for future neurofeedback approaches that aim, for example, the training of focused attention in disorders such as ADHD.

  18. Dissociable Patterns of Neural Activity during Response Inhibition in Depressed Adolescents with and without Suicidal Behavior

    Science.gov (United States)

    Pan, Lisa A.; Batezati-Alves, Silvia C.; Almeida, Jorge R. C.; Segreti, AnnaMaria; Akkal, Dalila; Hassel, Stefanie; Lakdawala, Sara; Brent, David A.; Phillips, Mary L.

    2011-01-01

    Objectives: Impaired attentional control and behavioral control are implicated in adult suicidal behavior. Little is known about the functional integrity of neural circuitry supporting these processes in suicidal behavior in adolescence. Method: Functional magnetic resonance imaging was used in 15 adolescent suicide attempters with a history of…

  19. Neural response to alcohol taste cues in youth : Effects of the OPRM1 gene

    NARCIS (Netherlands)

    Korucuoglu, Ozlem; Gladwin, Thomas E.; Baas, Frank; Mocking, Roel J. T.; Ruhé, Henricus G.; Groot, Paul F. C.; Wiers, Reinout W.

    2017-01-01

    Genetic variations in the mu-opioid receptor (OPRM1) gene have been related to high sensitivity to rewarding effects of alcohol. The current study focuses on the neural circuitry underlying this phenomenon using an alcohol versus water taste-cue reactivity paradigm in a young sample at relatively

  20. Comparative transcriptomics of the model mushroom Coprinopsis cinerea reveals tissue-specific armories and a conserved circuitry for sexual development.

    Science.gov (United States)

    Plaza, David Fernando; Lin, Chia-Wei; van der Velden, Niels Sebastiaan Johannes; Aebi, Markus; Künzler, Markus

    2014-06-19

    It is well known that mushrooms produce defense proteins and secondary metabolites against predators and competitors; however, less is known about the correlation between the tissue-specific expression and the target organism (antagonist) specificity of these molecules. In addition, conserved transcriptional circuitries involved in developing sexual organs in fungi are not characterized, despite the growing number of gene expression datasets available from reproductive and vegetative tissue. The aims of this study were: first, to evaluate the tissue specificity of defense gene expression in the model mushroom Coprinopsis cinerea and, second, to assess the degree of conservation in transcriptional regulation during sexual development in basidiomycetes. In order to characterize the regulation in the expression of defense loci and the transcriptional circuitries controlling sexual reproduction in basidiomycetes, we sequenced the poly (A)-positive transcriptome of stage 1 primordia and vegetative mycelium of C. cinerea A43mutB43mut. Our data show that many genes encoding predicted and already characterized defense proteins are differentially expressed in these tissues. The predicted specificity of these proteins with regard to target organisms suggests that their expression pattern correlates with the type of antagonists these tissues are confronted with. Accordingly, we show that the stage 1 primordium-specific protein CC1G_11805 is toxic to insects and nematodes. Comparison of our data to analogous data from Laccaria bicolor and Schizophyllum commune revealed that the transcriptional regulation of nearly 70 loci is conserved and probably subjected to stabilizing selection. A Velvet domain-containing protein was found to be up-regulated in all three fungi, providing preliminary evidence of a possible role of the Velvet protein family in sexual development of basidiomycetes. The PBS-soluble proteome of C. cinerea primordia and mycelium was analyzed by shotgun LC

  1. Brain and language: evidence for neural multifunctionality.

    Science.gov (United States)

    Cahana-Amitay, Dalia; Albert, Martin L

    2014-01-01

    This review paper presents converging evidence from studies of brain damage and longitudinal studies of language in aging which supports the following thesis: the neural basis of language can best be understood by the concept of neural multifunctionality. In this paper the term "neural multifunctionality" refers to incorporation of nonlinguistic functions into language models of the intact brain, reflecting a multifunctional perspective whereby a constant and dynamic interaction exists among neural networks subserving cognitive, affective, and praxic functions with neural networks specialized for lexical retrieval, sentence comprehension, and discourse processing, giving rise to language as we know it. By way of example, we consider effects of executive system functions on aspects of semantic processing among persons with and without aphasia, as well as the interaction of executive and language functions among older adults. We conclude by indicating how this multifunctional view of brain-language relations extends to the realm of language recovery from aphasia, where evidence of the influence of nonlinguistic factors on the reshaping of neural circuitry for aphasia rehabilitation is clearly emerging.

  2. Mapping of pain circuitry in early post-natal development using manganese-enhanced MRI in rats.

    Science.gov (United States)

    Sperry, M M; Kandel, B M; Wehrli, S; Bass, K N; Das, S R; Dhillon, P S; Gee, J C; Barr, G A

    2017-06-03

    Premature or ill full-term infants are subject to a number of noxious procedures as part of their necessary medical care. Although we know that human infants show neural changes in response to such procedures, we know little of the sensory or affective brain circuitry activated by pain. In rodent models, the focus has been on spinal cord and, more recently, midbrain and medulla. The present study assesses activation of brain circuits using manganese-enhanced magnetic resonance imaging (MEMRI). Uptake of manganese, a paramagnetic contrast agent that is transported across active synapses and along axons, was measured in response to a hindpaw injection of dilute formalin in 12-day-old rat pups, the age at which rats begin to show aversion learning and which is roughly the equivalent of full-term human infants. Formalin induced the oft-reported biphasic response at this age and induced a conditioned aversion to cues associated with its injection, thus demonstrating the aversiveness of the stimulation. Morphometric analyses, structural equation modeling and co-expression analysis showed that limbic and sensory paths were activated, the most prominent of which were the prefrontal and anterior cingulate cortices, nucleus accumbens, amygdala, hypothalamus, several brainstem structures, and the cerebellum. Therefore, both sensory and affective circuits, which are activated by pain in the adult, can also be activated by noxious stimulation in 12-day-old rat pups. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Neural correlates of task switching in paternal 15q11-q13 deletion Prader-Willi syndrome.

    Science.gov (United States)

    Woodcock, Kate A; Humphreys, Glyn W; Oliver, Chris; Hansen, Peter C

    2010-12-02

    We report a first study of brain activity linked to task switching in individuals with Prader-Willi syndrome (PWS). PWS individuals show a specific cognitive deficit in task switching which may be associated with the display of temper outbursts and repetitive questioning. The performance of participants with PWS and typically developing controls was matched in a cued task switching procedure, and brain activity was contrasted on switching and non-switching blocks using fMRI. Individuals with PWS did not show the typical frontal-parietal pattern of neural activity associated with switching blocks, with significantly reduced activation in regions of the posterior parietal and ventromedial prefrontal cortices. We suggest that this is linked to a difficulty in PWS in setting appropriate attentional weights to enable task-set reconfiguration. In addition to this, PWS individuals did not show the typical pattern of deactivation, with significantly less deactivation in an anterior region of the ventromedial prefrontal cortex. One plausible explanation for this is that individuals with PWS show dysfunction within the default mode network, which has been linked to attentional control. The data point to functional changes in the neural circuitry supporting task switching in PWS even when behavioural performance is matched to controls and thus highlight neural mechanisms that may be involved in a specific pathway between genes, cognition and behaviour. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Neural division of labor in reading is constrained by culture: a training study of reading Chinese characters.

    Science.gov (United States)

    Zhao, Jingjing; Wang, Xiaoyi; Frost, Stephen J; Sun, Wan; Fang, Shin-Yi; Mencl, W Einar; Pugh, Kenneth R; Shu, Hua; Rueckl, Jay G

    2014-04-01

    Word reading in alphabetic language involves a cortical system with multiple components whose division of labor depends on the transparency of the writing system. To gain insight about the neural division of labor between phonology and semantics subserving word reading in Chinese, a deep non-alphabetic writing system, functional magnetic resonance imaging (fMRI) was used to investigate the effects of phonological and semantic training on the cortical circuitry for oral naming of Chinese characters. In a training study, we examined whether a training task that differentially focused readers' attention on the phonological or semantic properties of a Chinese character changes the patterns of cortical activation that was evoked by that character in a subsequent naming task. Our imaging results corroborate that the cortical regions underlying reading in Chinese largely overlap the left-hemisphere reading system responsible for reading in alphabetic languages, with some cortical regions in the left-hemisphere uniquely recruited for reading in Chinese. However, in contrast to findings from studies of English word naming, we observed considerable overlap in the neural activation patterns associated with phonological and semantic training on naming Chinese characters, which we suggest may reflect a balanced neural division of labor between phonology and semantics in Chinese character reading. The equitable division of labor for Chinese reading might be driven by the special statistical structure of the writing system, which includes equally systematic mappings in the correspondences between written forms and their pronunciations and meanings. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Abnormalities in the effective connectivity of visuothalamic circuitry in schizophrenia.

    Science.gov (United States)

    Iwabuchi, S J; Palaniyappan, L

    2017-05-01

    Sensory-processing deficits appear crucial to the clinical expression of symptoms of schizophrenia. The visual cortex displays both dysconnectivity and aberrant spontaneous activity in patients with persistent symptoms and cognitive deficits. In this paper, we examine visual cortex in the context of the remerging notion of thalamic dysfunction in schizophrenia. We examined specific regional and longer-range abnormalities in sensory and thalamic circuits in schizophrenia, and whether these patterns are strong enough to discriminate symptomatic patients from controls. Using publicly available resting fMRI data of 71 controls and 62 schizophrenia patients, we derived conjunction maps of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) to inform further seed-based Granger causality analysis (GCA) to study effective connectivity patterns. ReHo, fALFF and GCA maps were entered into a multiple kernel learning classifier, to determine whether patterns of local and effective connectivity can differentiate controls from patients. Visual cortex shows both ReHo and fALFF reductions in patients. Visuothalamic effective connectivity in patients was significantly reduced. Local connectivity (ReHo) patterns discriminated patients from controls with the highest level of accuracy of 80.32%. Both the inflow and outflow of Granger causal information between visual cortex and thalamus is affected in schizophrenia; this occurs in conjunction with highly discriminatory but localized dysconnectivity and reduced neural activity within the visual cortex. This may explain the visual-processing deficits that are present despite symptomatic remission in schizophrenia.

  6. The neural dynamics of speech perception: Dissociable networks for processing linguistic content and monitoring speaker turn-taking.

    Science.gov (United States)

    Foti, Dan; Roberts, Felicia

    2016-01-01

    The neural circuitry for speech perception is well-characterized, yet the temporal dynamics therein are largely unknown. This timing information is critical in that spoken language almost always occurs in the context of joint speech (i.e., conversations) where effective communication requires the precise timing of speaker turn-taking-a core aspect of prosody. Here, we used event-related potentials to characterize neural activity elicited by conversation stimuli within a large, unselected adult sample (N=115). We focused on two stages of speech perception: inter-speaker gaps and speaker responses. We found activation in two known speech perception networks, with functional and neuroanatomical specificity: silence during inter-speaker gaps primarily activated the posterior pathway involving the supramarginal gyrus and premotor cortex, whereas hearing speaker responses primarily activated the anterior pathway involving the superior temporal gyrus. These data provide the first direct evidence that the posterior pathway is uniquely involved in monitoring speaker turn-taking. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Method, apparatus and system to compensate for drift by physically unclonable function circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason

    2016-11-22

    Techniques and mechanisms to detect and compensate for drift by a physically uncloneable function (PUF) circuit. In an embodiment, first state information is registered as reference information to be made available for subsequent evaluation of whether drift by PUF circuitry has occurred. The first state information is associated with a first error correction strength. The first state information is generated based on a first PUF value output by the PUF circuitry. In another embodiment, second state information is determined based on a second PUF value that is output by the PUF circuitry. An evaluation of whether drift has occurred is performed based on the first state information and the second state information, the evaluation including determining whether a threshold error correction strength is exceeded concurrent with a magnitude of error being less than the first error correction strength.

  8. Central neural control of thermoregulation and brown adipose tissue.

    Science.gov (United States)

    Morrison, Shaun F

    2016-04-01

    Central neural circuits orchestrate the homeostatic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response. This review summarizes the experimental underpinnings of our current model of the CNS pathways controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction controlling heat loss, and shivering and brown adipose tissue for thermogenesis. The activation of these effectors is regulated by parallel but distinct, effector-specific, core efferent pathways within the CNS that share a common peripheral thermal sensory input. Via the lateral parabrachial nucleus, skin thermal afferent input reaches the hypothalamic preoptic area to inhibit warm-sensitive, inhibitory output neurons which control heat production by inhibiting thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to thermogenesis-controlling premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation of spinal circuits necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus sympathetic premotor neurons controlling cutaneous vasoconstriction. The model proposed for central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation and elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Identification of β-Dystrobrevin as a Direct Target of miR-143: Involvement in Early Stages of Neural Differentiation.

    Science.gov (United States)

    Quaranta, Maria Teresa; Spinello, Isabella; Paolillo, Rosa; Macchia, Gianfranco; Boe, Alessandra; Ceccarini, Marina; Labbaye, Catherine; Macioce, Pompeo

    2016-01-01

    Duchenne Muscular Dystrophy, a genetic disorder that results in a gradual breakdown of muscle, is associated to mild to severe cognitive impairment in about one-third of dystrophic patients. The brain dysfunction is independent of the muscular pathology, occurs early, and is most likely due to defects in the assembly of the Dystrophin-associated Protein Complex (DPC) during embryogenesis. We have recently described the interaction of the DPC component β-dystrobrevin with members of complexes that regulate chromatin dynamics, and suggested that β-dystrobrevin may play a role in the initiation of neuronal differentiation. Since oxygen concentrations and miRNAs appear as well to be involved in the cellular processes related to neuronal development, we have studied how these factors act on β-dystrobrevin and investigated the possibility of their functional interplay using the NTera-2 cell line, a well-established model for studying neurogenesis. We followed the pattern of expression and regulation of β-dystrobrevin during the early stages of neuronal differentiation induced by exposure to retinoic acid (RA) under hypoxia as compared with normoxia, and found that β-dystrobrevin expression is regulated during RA-induced differentiation of NTera-2 cells. We also found that β-dystrobrevin pattern is delayed under hypoxic conditions, together with a delay in the differentiation and an increase in the proliferation rate of cells. We identified miRNA-143 as a direct regulator of β-dystrobrevin expression, demonstrated that β-dystrobrevin is expressed in the nucleus and showed that, in line with our previous in vitro results, β-dystrobrevin is a repressor of synapsin I in live cells. Altogether the newly identified regulatory pathway miR-143/β-dystrobrevin/synapsin I provides novel insights into the functions of β-dystrobrevin and opens up new perspectives for elucidating the molecular mechanisms underlying the neuronal involvement in muscular dystrophy.

  10. Triglyceride sensing in the reward circuitry: A new insight in feeding behaviour regulation.

    Science.gov (United States)

    Cansell, Celine; Luquet, Serge

    2016-01-01

    In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Obesity often involves a behavioural component in which, similar to drugs abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. The hypothalamus is one of the primary integration sites of circulating energy-related signals like leptin or ghrelin and is therefore considered as one of the main central regulators of energy balance. However, food intake is also modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a key actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable food and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the reward circuitry. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights

  11. Implicit sequence learning in juvenile anorexia nervosa: neural mechanisms and the impact of starvation.

    Science.gov (United States)

    Firk, Christine; Mainz, Verena; Schulte-Ruether, Martin; Fink, Gereon; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2015-11-01

    Previous studies have reported that cognitive deficits occur in patients with anorexia nervosa (AN) and that these deficits may represent a predisposition towards developing AN or perpetuate the disorder. Specifically, dysfunctional implicit learning may contribute to the development of highly resistant dieting behaviours that are fundamental to the persistence of the disorder. Thus, the aims of this study were (a) to investigate implicit sequence learning in adolescent patients with AN before and after weight recovery and (b) to elucidate the associated neural mechanisms in acute AN relative to healthy controls. In a behavioural study, implicit sequence learning was assessed using a serial reaction time task in 27 adolescents with AN before (T1) and after weight recovery (T2) compared with age-matched healthy controls (HC) who were assessed at similar time intervals. The neural correlates of implicit sequence learning were subsequently investigated in 19 AN patients shortly after they were admitted to the hospital and 20 HC using functional magnetic resonance imaging (fMRI). At T1, AN patients showed reduced sequence learning compared with HC. However, no behavioural differences between HC and AN patients were found at T2. At the neural level, acute AN patients showed reduced thalamic activation during sequence learning compared with HC subjects. Our data suggest that the impaired implicit learning observed in adolescent AN patients before weight gain is a state-related dysfunction that normalises with weight gain. Thus, implicit learning deficits do not appear to represent a predisposition towards developing AN; rather, these deficits should be considered when planning psychotherapeutic interventions for acute AN. Reduced thalamic activation during the acute stage of AN may indicate a starvation-induced dysfunction of the neural circuitry that is involved in behavioural flexibility. © 2015 Association for Child and Adolescent Mental Health.

  12. Medial preoptic area interactions with dopamine neural systems in the control of the onset and maintenance of maternal behavior in rats.

    Science.gov (United States)

    Numan, Michael; Stolzenberg, Danielle S

    2009-01-01

    The medial preoptic area (MPOA) and dopamine (DA) neural systems interact to regulate maternal behavior in rats. Two DA systems are involved: the mesolimbic DA system and the incerto-hypothalamic DA system. The hormonally primed MPOA regulates the appetitive aspects of maternal behavior by activating mesolimbic DA input to the shell region of the nucleus accumbens (NAs). DA action on MPOA via the incerto-hypothalamic system may interact with steroid and peptide hormone effects so that MPOA output to the mesolimbic DA system is facilitated. Neural oxytocin facilitates the onset of maternal behavior by actions at critical nodes in this circuitry. DA-D1 receptor agonist action on either the MPOA or NAs can substitute for the effects of estradiol in stimulating the onset of maternal behavior, suggesting an overlap in underlying cellular mechanisms between estradiol and DA. Maternal memory involves the neural plasticity effects of mesolimbic DA activity. Finally, early life stressors may affect the development of MPOA-DA interactions and maternal behavior.

  13. A cortical neural prosthesis for restoring and enhancing memory

    Science.gov (United States)

    Berger, Theodore W.; Hampson, Robert E.; Song, Dong; Goonawardena, Anushka; Marmarelis, Vasilis Z.; Deadwyler, Sam A.

    2011-08-01

    A primary objective in developing a neural prosthesis is to replace neural circuitry in the brain that no longer functions appropriately. Such a goal requires artificial reconstruction of neuron-to-neuron connections in a way that can be recognized by the remaining normal circuitry, and that promotes appropriate interaction. In this study, the application of a specially designed neural prosthesis using a multi-input/multi-output (MIMO) nonlinear model is demonstrated by using trains of electrical stimulation pulses to substitute for MIMO model derived ensemble firing patterns. Ensembles of CA3 and CA1 hippocampal neurons, recorded from rats performing a delayed-nonmatch-to-sample (DNMS) memory task, exhibited successful encoding of trial-specific sample lever information in the form of different spatiotemporal firing patterns. MIMO patterns, identified online and in real-time, were employed within a closed-loop behavioral paradigm. Results showed that the model was able to predict successful performance on the same trial. Also, MIMO model-derived patterns, delivered as electrical stimulation to the same electrodes, improved performance under normal testing conditions and, more importantly, were capable of recovering performance when delivered to animals with ensemble hippocampal activity compromised by pharmacologic blockade of synaptic transmission. These integrated experimental-modeling studies show for the first time that, with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time diagnosis and manipulation of the encoding process can restore and even enhance cognitive, mnemonic processes.

  14. A cortical neural prosthesis for restoring and enhancing memory.

    Science.gov (United States)

    Berger, Theodore W; Hampson, Robert E; Song, Dong; Goonawardena, Anushka; Marmarelis, Vasilis Z; Deadwyler, Sam A

    2011-08-01

    A primary objective in developing a neural prosthesis is to replace neural circuitry in the brain that no longer functions appropriately. Such a goal requires artificial reconstruction of neuron-to-neuron connections in a way that can be recognized by the remaining normal circuitry, and that promotes appropriate interaction. In this study, the application of a specially designed neural prosthesis using a multi-input/multi-output (MIMO) nonlinear model is demonstrated by using trains of electrical stimulation pulses to substitute for MIMO model derived ensemble firing patterns. Ensembles of CA3 and CA1 hippocampal neurons, recorded from rats performing a delayed-nonmatch-to-sample (DNMS) memory task, exhibited successful encoding of trial-specific sample lever information in the form of different spatiotemporal firing patterns. MIMO patterns, identified online and in real-time, were employed within a closed-loop behavioral paradigm. Results showed that the model was able to predict successful performance on the same trial. Also, MIMO model-derived patterns, delivered as electrical stimulation to the same electrodes, improved performance under normal testing conditions and, more importantly, were capable of recovering performance when delivered to animals with ensemble hippocampal activity compromised by pharmacologic blockade of synaptic transmission. These integrated experimental-modeling studies show for the first time that, with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time diagnosis and manipulation of the encoding process can restore and even enhance cognitive, mnemonic processes.

  15. Effects of age and MAOA genotype on the neural processing of social rejection.

    Science.gov (United States)

    Sebastian, C L; Roiser, J P; Tan, G C Y; Viding, E; Wood, N W; Blakemore, S-J

    2010-08-01

    Adolescents are often sensitive to peer rejection, a factor that might contribute to the risk of affective disorder in this age group. Previous studies suggest a significant overlap among socioaffective brain regions involved in the response to social rejection, regions continuing to develop functionally during adolescence and regions influenced by monoamine oxidase A (MAOA) polymorphism. The current study investigated whether the neural response to social rejection is functionally immature in adolescents compared with adults, and whether these responses are modulated by MAOA genotype. Blood-oxygen-level-dependent response was measured with functional magnetic resonance imaging during a rejection-themed emotional Stroop task in 19 adolescents (aged 14-16) and 16 adults (aged 23-28) genotyped for MAOA polymorphism. Similar numbers of MAOA-L and MAOA-H carriers were recruited to maximize power to detect genotype effects. Main effects of rejection stimuli (relative to neutral and acceptance control stimuli) were seen in predicted socioaffective brain regions. Adolescents did not show the adult pattern of modulation by rejection stimuli in the right ventrolateral prefrontal cortex, suggesting continued functional maturation of this regulatory region during adolescence. Age and genotype interacted in the left amygdala, in which the predicted effect of genotype on responses to rejection stimuli was seen in the adults, but not in the adolescents. The data suggest continued functional development of the circuitry underlying the processing of social rejection between adolescence and adulthood, and show that the effects of MAOA genotype on neural responses may vary with age.

  16. Inherently stochastic spiking neurons for probabilistic neural computation

    KAUST Repository

    Al-Shedivat, Maruan

    2015-04-01

    Neuromorphic engineering aims to design hardware that efficiently mimics neural circuitry and provides the means for emulating and studying neural systems. In this paper, we propose a new memristor-based neuron circuit that uniquely complements the scope of neuron implementations and follows the stochastic spike response model (SRM), which plays a cornerstone role in spike-based probabilistic algorithms. We demonstrate that the switching of the memristor is akin to the stochastic firing of the SRM. Our analysis and simulations show that the proposed neuron circuit satisfies a neural computability condition that enables probabilistic neural sampling and spike-based Bayesian learning and inference. Our findings constitute an important step towards memristive, scalable and efficient stochastic neuromorphic platforms. © 2015 IEEE.

  17. Some modifications of electric circuitry for internal friction measurements of U-shape specimens

    OpenAIRE

    Osamu, Yoshinari; M., KOIWA; H., Sugawara; I., SATO

    1980-01-01

    Some modifications of the electric circuitry are described for the apparatus of the internal friction measurement of thin wire specimens; the apparatus has been developed by Franklin et al. The improved apparatus has been successfully used in the internal friction measurements of cold‐worked vanadium specimens.

  18. Analysis and simulation of the SLD WIC (Warm Iron Calorimeter) PADS hybrid preamplifier circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Fox, J.D.; Horelick, D.

    1990-10-01

    The SLD PADS electronics consist of over 9000 channels of charge-sensitive preamplifiers followed by integrated sample/hold data storage, digitizing, and readout circuitry. This paper uses computer simulation techniques to analyze critical performance parameters of the preamplifier hybrid including its interactions with the detector system. Simulation results are presented and verified with measured performance. 6 refs., 9 figs.

  19. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling

    2010-11-01

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  20. 78 FR 41079 - Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same

    Science.gov (United States)

    2013-07-09

    ... COMMISSION Certain Semiconductor Chips With Dram Circuitry, and Modules and Products Containing Same AGENCY... invalid. The same day Nanya filed a petition for review of a number of the determinations in the ID that.... Patent Publication No. 2006/0126401 to Ba (RX-107) should or should not have the same number of legs? b...

  1. Redox control of enzymatic functions: The electronics of life's circuitry.

    Science.gov (United States)

    Bonini, Marcelo G; Consolaro, Marcia E L; Hart, Peter C; Mao, Mao; de Abreu, Andre Luelsdorf Pimenta; Master, Alyssa M

    2014-03-26

    The field of redox biology has changed tremendously over the past 20 years. Formerly regarded as bi-products of the aerobic metabolism exclusively involved in tissue damage, reactive oxygen species (ROS) are now recognized as active participants of cell signaling events in health and in disease. In this sense, ROS and the more recently defined reactive nitrogen species (RNS) are, just like hormones and second messengers, acting as fundamental orchestrators of cell signaling pathways. The chemical modification of enzymes by ROS and RNS (that result in functional enzymatic alterations) accounts for a considerable fraction of the transient and persistent perturbations imposed by variations in oxidant levels. Upregulation of ROS and RNS in response to stress is a common cellular response that foments adaptation to a variety of physiologic alterations (hypoxia, hyperoxia, starvation, and cytokine production). Frequently, these are beneficial and increase the organisms' resistance against subsequent acute stress (preconditioning). Differently, the sustained ROS/RNS-dependent rerouting of signaling produces irreversible alterations in cellular functioning, often leading to pathogenic events. Thus, the duration and reversibility of protein oxidations define whether complex organisms remain "electronically" healthy. Among the 20 essential amino acids, four are particularly susceptible to oxidation: cysteine, methionine, tyrosine, and tryptophan. Here, we will critically review the mechanisms, implications, and repair systems involved in the redox modifications of these residues in proteins while analyzing well-characterized prototypic examples. Occasionally, we will discuss potential consequences of amino acid oxidation and speculate on the biologic necessity for such events in the context of adaptative redox signaling. © 2014 IUBMB Life, 2014. © 2014 International Union of Biochemistry and Molecular Biology.

  2. Normative data on development of neural and behavioral mechanisms underlying attention orienting toward social-emotional stimuli: An exploratory study

    OpenAIRE

    Lindstrom, Kara; Guyer, Amanda E; Mogg, Karin; Bradley, Brendan P.; Fox, Nathan A.; Ernst, Monique; Nelson, Eric E.; Leibenluft, Ellen; Britton, Jennifer C.; Monk, Christopher S.; Pine, Daniel S.; Bar-Haim, Yair

    2009-01-01

    The ability of positive and negative facial signals to influence attention orienting is crucial to social functioning. Given the dramatic developmental change in neural architecture supporting social function, positive and negative facial cues may influence attention orienting differently in relatively young or old individuals. However, virtually no research examines such age-related differences in the neural circuitry supporting attention orienting to emotional faces. We examined age-related...

  3. Hilar mossy cell circuitry controlling dentate granule cell excitability

    Directory of Open Access Journals (Sweden)

    Seiichiro eJinde

    2013-02-01

    Full Text Available Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability – the dormant basket cell and the irritable mossy cell hypotheses. The dormant basket cell hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The irritable mossy cell hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

  4. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  5. Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Report 3

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Jr, Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shelton, Jacob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

    2015-03-01

    As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios when human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments because of the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is a report of the activities involving Task 3 of the Nuclear Energy Enabling Technologies (NEET) 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays [1]. Evaluation of the performance of the system for both pre- and post-irradiation as well as operation at elevated temperature will be performed. Detailed performance of the system will be documented to ensure the design meets requirements prior to any extended evaluation. A suite of tests will be developed which will allow evaluation before and after irradiation and during temperature. Selection of the radiation exposure facilities will be determined in the early phase of the project. Radiation exposure will consist of total integrated dose (TID) up to 200 kRad or above with several intermediate doses during test. Dose rates will be in various ranges determined by the facility that will be used with a target of 30 kRad/hr. Many samples of the pre-commercial devices to be used will have been tested in previous projects to doses of at least 300 kRad and temperatures up to 125C. The complete systems will therefore be tested for performance at intermediate doses. Extended temperature testing will be performed up to the limit of the commercial sensors. The test suite performed at each test point will consist of operational testing of the three basic

  6. Sex differences in the development of emotion circuitry in adolescents at risk for substance abuse: a longitudinal fMRI study.

    Science.gov (United States)

    Hardee, Jillian E; Cope, Lora M; Munier, Emily C; Welsh, Robert C; Zucker, Robert A; Heitzeg, Mary M

    2017-06-01

    There is substantial evidence for behavioral sex differences in risk trajectories for alcohol and substance use, with internalizing factors such as negative affectivity contributing more to female risk. Because the neural development of emotion circuitry varies between males and females across adolescence, it represents a potential mechanism by which underlying neurobiology contributes to risk for substance use. Longitudinal functional magnetic resonance imaging was conducted in males and females (n = 18 each) with a family history of alcohol use disorders starting at ages 8-13 years. Participants performed an affective word task during functional magnetic resonance imaging at 1- to 2-year intervals, covering the age range of 8.5-17.6 years (3-4 scans per participant). Significant age-related sex differences were found in the right amygdala and right precentral gyrus for the negative vs neutral word condition. Males showed a significant decrease in both amygdala and precentral gyrus activation with age, whereas the response in females persisted. The subjective experience of internalizing symptomatology significantly increased with age for females but not for males. Taken together, these results reveal sex differences in negative affect processing in at-risk adolescents, and offer longitudinal neural evidence for female substance use risk through internalizing pathways. © The Author (2017). Published by Oxford University Press.

  7. Epsilon-Near-Zero Photonics Wires for Mid-Infrared Optical Lumped Circuitry

    CERN Document Server

    Liu, Runyu; Zhong, Yujun; Podolskiy, Viktor; Wasserman, Daniel

    2016-01-01

    There has been recent interest in the development of optical analogues of lumped element circuitry, where optical elements act as effective optical inductors, capacitors, and resistors. Such optical circuitry requires the photonic equivalent of electrical wires, structures able carry optical frequency signals to and from the lumped circuit elements while simultaneously maintaining signal carrier wavelengths much larger than the size of the lumped elements. Here we demonstrate the design, fabrication, and characterization of hybrid metal/doped-semiconductor 'photonic wires' operating at optical frequencies with effective indices of propagation near-zero. Our samples are characterized by polarization and angle-dependent FTIR spectroscopy and modeled by finite element methods and rigorous coupled wave analysis. We demonstrate coupling to such photonic wires from free space, and show the effective wavelength of the excited mode to be approximately an order of magnitude larger than the free-space wavelength of our...

  8. Stitching Codeable Circuits: High School Students' Learning About Circuitry and Coding with Electronic Textiles

    Science.gov (United States)

    Litts, Breanne K.; Kafai, Yasmin B.; Lui, Debora A.; Walker, Justice T.; Widman, Sari A.

    2017-10-01

    Learning about circuitry by connecting a battery, light bulb, and wires is a common activity in many science classrooms. In this paper, we expand students' learning about circuitry with electronic textiles, which use conductive thread instead of wires and sewable LEDs instead of lightbulbs, by integrating programming sensor inputs and light outputs and examining how the two domains interact. We implemented an electronic textiles unit with 23 high school students ages 16-17 years who learned how to craft and code circuits with the LilyPad Arduino, an electronic textile construction kit. Our analyses not only confirm significant increases in students' understanding of functional circuits but also showcase students' ability in designing and remixing program code for controlling circuits. In our discussion, we address opportunities and challenges of introducing codeable circuit design for integrating maker activities that include engineering and computing into classrooms.

  9. Optogenetics in Silicon: A Neural Processor for Predicting Optically Active Neural Networks.

    Science.gov (United States)

    Junwen Luo; Nikolic, Konstantin; Evans, Benjamin D; Na Dong; Xiaohan Sun; Andras, Peter; Yakovlev, Alex; Degenaar, Patrick

    2017-02-01

    We present a reconfigurable neural processor for real-time simulation and prediction of opto-neural behaviour. We combined a detailed Hodgkin-Huxley CA3 neuron integrated with a four-state Channelrhodopsin-2 (ChR2) model into reconfigurable silicon hardware. Our architecture consists of a Field Programmable Gated Array (FPGA) with a custom-built computing data-path, a separate data management system and a memory approach based router. Advancements over previous work include the incorporation of short and long-term calcium and light-dependent ion channels in reconfigurable hardware. Also, the developed processor is computationally efficient, requiring only 0.03 ms processing time per sub-frame for a single neuron and 9.7 ms for a fully connected network of 500 neurons with a given FPGA frequency of 56.7 MHz. It can therefore be utilized for exploration of closed loop processing and tuning of biologically realistic optogenetic circuitry.

  10. Functional role for cortical-striatal circuitry in modulating alcohol self-administration.

    Science.gov (United States)

    Jaramillo, Anel A; Randall, Patrick A; Stewart, Spencer; Fortino, Brayden; Van Voorhies, Kalynn; Besheer, Joyce

    2018-03-01

    The cortical-striatal brain circuitry is heavily implicated in drug-use. As such, the present study investigated the functional role of cortical-striatal circuitry in modulating alcohol self-administration. Given that a functional role for the nucleus accumbens core (AcbC) in modulating alcohol-reinforced responding has been established, we sought to test the role of cortical brain regions with afferent projections to the AcbC: the medial prefrontal cortex (mPFC) and the insular cortex (IC). Long-Evans rats were trained to self-administer alcohol (15% alcohol (v/v)+2% sucrose (w/v)) during 30 min sessions. To test the functional role of the mPFC or IC, we utilized a chemogenetic technique (hM4D i -Designer Receptors Activation by Designer Drugs) to silence neuronal activity prior to an alcohol self-administration session. Additionally, we chemogenetically silenced mPFC→AcbC or IC→AcbC projections, to investigate the role of cortical-striatal circuitry in modulating alcohol self-administration. Chemogenetically silencing the mPFC decreased alcohol self-administration, while silencing the IC increased alcohol self-administration, an effect absent in mCherry-Controls. Interestingly, silencing mPFC→AcbC projections had no effect on alcohol self-administration. In contrast, silencing IC→AcbC projections decreased alcohol self-administration, in a reinforcer-specific manner as there was no effect in rats trained to self-administer sucrose (0.8%, w/v). Additionally, no change in self-administration was observed in the mCherry-Controls. Together these data demonstrate the complex role of the cortical-striatal circuitry while implicating a role for the insula-striatal circuit in modulating ongoing alcohol self-administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Neural Computations in Binaural Hearing

    Science.gov (United States)

    Wagner, Hermann

    Binaural hearing helps humans and animals to localize and unmask sounds. Here, binaural computations in the barn owl's auditory system are discussed. Barn owls use the interaural time difference (ITD) for azimuthal sound localization, and they use the interaural level difference (ELD) for elevational sound localization. ITD and ILD and their precursors are processed in separate neural pathways, the time pathway and the intensity pathway, respectively. Representation of ITD involves four main computational steps, while the representation of ILD is accomplished in three steps. In the discussion neural processing in the owl's auditory system is compared with neural computations present in mammals.

  12. Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology.

    Science.gov (United States)

    Salamone, John D; Yohn, Samantha E; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

    2016-05-01

    Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson's disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision

  13. Neural Response to Catecholamine Depletion in Unmedicated Subjects With Major Depressive Disorder in Remission and Healthy Subjects

    Science.gov (United States)

    Hasler, Gregor; Fromm, Stephen; Carlson, Paul J.; Luckenbaugh, David A.; Waldeck, Tracy; Geraci, Marilla; Roiser, Jonathan P.; Neumeister, Alexander; Meyers, Noah; Charney, Dennis S.; Drevets, Wayne C.

    2009-01-01

    Context The pathophysiologic mechanism of major depressive disorder (MDD) has been consistently associated with altered catecholaminergic function, especially with decreased dopamine neurotransmission, by various sources of largely indirect evidence. An instructive paradigm for more directly investigating the relationship between catecholaminergic function and depression has involved the mood response to experimental catecholamine depletion (CD). Objectives To determine whether catecholaminergic dysfunction represents a trait abnormality in MDD and to identify brain circuitry abnormalities involved in the pathophysiologic mechanism of MDD. Design Randomized, double-blind, placebo-controlled, crossover, single-site experimental trial. Setting Psychiatric outpatient clinic. Participants Fifteen unmedicated subjects with MDD in full remission (hereinafter referred to as RMDD subjects) and 13 healthy controls. Intervention Induction of CD by oral administration of α-methylparatyrosine. Sham depletion used identical capsules containing hydrous lactose. Main Outcome Measures Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of CD and sham depletion. Behavioral assessments included the Montgomery-Asberg Depression Rating Scale and the Snaith-Hamilton Pleasure Scale (anhedonia). Results Depressive and anhedonic symptoms increased during CD to a greater extent in RMDD subjects than in controls. In both groups, CD increased metabolism in the anteroventral striatum and decreased metabolism in the orbital gyri. In a limbic-cortical-striatal-pallidal-thalamic network previously implicated in MDD, composed of the ventromedial frontal polar cortex, midcingulate and subgenual anterior cingulate cortex, temporopolar cortex, ventral striatum, and thalamus, metabolism increased in RMDD subjects but decreased or remained unchanged in controls. Metabolic changes induced by CD in the left ventromedial frontal polar cortex

  14. A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry

    Science.gov (United States)

    Gee, Dylan G.; Humphreys, Kathryn L.; Flannery, Jessica; Goff, Bonnie; Telzer, Eva H.; Shapiro, Mor; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim

    2013-01-01

    Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections. PMID:23467374

  15. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

    Directory of Open Access Journals (Sweden)

    Dichter Gabriel S

    2012-07-01

    Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

  16. The effects of acute stress exposure on neural correlates of Pavlovian conditioning with monetary gains and losses

    Directory of Open Access Journals (Sweden)

    Andrea H Lewis

    2014-05-01

    Full Text Available Pavlovian conditioning involves the association of an inherently neutral stimulus with an appetitive or aversive outcome, such that the neutral stimulus itself acquires reinforcing properties. Across species, this type of learning has been shown to involve subcortical brain regions such as the striatum and the amygdala. It is less clear, however, how the neural circuitry involved in the acquisition of Pavlovian contingencies in humans is affected by acute stress. In the current study, we investigate the effect of acute stress exposure on Pavlovian conditioning using monetary reinforcers. Participants underwent a partial reinforcement conditioning procedure in which neutral stimuli were paired with high and low magnitude monetary gains and losses. A between-subjects design was used, such that half of the participants were exposed to cold stress while the remaining participants were exposed to a no stress control procedure. Cortisol measurements and subjective ratings were used as measures of stress. We observed an interaction between stress, valence and magnitude in the ventral striatum, with the peak in the putamen. More specifically, the stress group exhibited an increased sensitivity to magnitude in the gain domain. This effect was driven by those participants who experienced a larger increase in circulating cortisol levels in response to the stress manipulation. Taken together, these results suggest that acute stress can lead to individual differences in circulating cortisol levels which influence brain regions involved in associative learning such as the ventral striatum.

  17. Enhanced food anticipatory activity associated with enhanced activation of extrahypothalamic neural pathways in serotonin2C receptor null mutant mice.

    Directory of Open Access Journals (Sweden)

    Jennifer L Hsu

    Full Text Available The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity. However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin(2C receptor (5-HT2CR null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways.

  18. Restructuring of basal ganglia circuitry and associated behaviors triggered by low striatal D2 receptor expression: implications for substance use disorders.

    Science.gov (United States)

    Dobbs, L K; Lemos, J C; Alvarez, V A

    2017-01-01

    Dopamine D2 receptors (D2Rs) consistently emerge as a critical substrate for the etiology of some major psychiatric disorders. Indeed, a central theory of substance use disorders (SUDs) postulates that a reduction in D2R levels in the striatum is a determining factor that confers vulnerability to abuse substances. A large number of clinical and preclinical studies strongly support this link between SUDs and D2Rs; however, identifying the mechanism by which low D2Rs facilitate SUDs has been hindered by the complexity of circuit connectivity, the heterogeneity of D2R expression and the multifaceted constellation of phenotypes observed in SUD patient. Animal models are well-suited for understanding the mechanisms because they allow access to the circuitry and the genetic tools that enable a dissection of the D2R heterogeneity. This review discusses recent findings on the functional role of D2Rs and highlights the distinctive contributions of D2Rs expressed on specific neuronal subpopulations to the behavioral responses to stimulant drugs. A circuit-wide restructuring of local and long-range inhibitory connectivity within the basal ganglia is observed in response to manipulation of striatal D2R levels and is accompanied by multiple alterations in dopamine-dependent behaviors. Collectively, these new findings provide compelling evidence for a critical role of striatal D2Rs in shaping basal ganglia connectivity; even among neurons that do not express D2Rs. These findings from animal models have deep clinical implications for SUD patients with low levels D2R availability where a similar restructuring of basal ganglia circuitry is expected to take place. © 2016 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

  19. Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

    Directory of Open Access Journals (Sweden)

    Christelle Anaclet

    2010-01-01

    Full Text Available Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle

  20. Potential Involvement of Draxin in the Axonal Projection of Cranial Nerves, Especially Cranial Nerve X, in the Chick Hindbrain.

    Science.gov (United States)

    Zhang, Sanbing; Cui, Huixian; Wang, Lei; Kang, Lin; Huang, Guannan; Du, Juan; Li, Sha; Tanaka, Hideaki; Su, Yuhong

    2016-07-01

    The appropriate projection of axons within the nervous system is a crucial component of the establishment of neural circuitry. Draxin is a repulsive axon guidance protein. Draxin has important functions in the guidance of three commissures in the central nervous system and in the migration of neural crest cells and dI3 interneurons in the chick spinal cord. Here, we report that the distribution of the draxin protein and the location of 23C10-positive areas have a strong temporal and spatial correlation. The overexpression of draxin, especially transmembrane draxin, caused 23C10-positive axon bundles to misproject in the dorsal hindbrain. In addition, the overexpression of transmembrane draxin caused abnormal formation of the ganglion crest of the IX and X cranial nerves, misprojection of some anti-human natural killer-1 (HNK-1)-stained structures in the dorsal roof of the hindbrain, and a simultaneous reduction in the efferent nerves of some motoneuron axons inside the hindbrain. Our data reveal that draxin might be involved in the fascicular projection of cranial nerves in the hindbrain. © 2016 The Histochemical Society.

  1. Neural mechanisms controlling seasonal reproduction: principles derived from the sheep model and its comparison with hamsters

    Science.gov (United States)

    Weems, Peyton W.; Goodman, Robert L.; Lehman, Michael N.

    2015-01-01

    Seasonal reproduction is a common adaptive strategy among mammals that allows for breeding to occur at times of the year when it is most advantageous for the subsequent survival and growth of offspring. A major mechanism responsible for seasonal reproduction is a striking increase in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the negative feedback effects of estradiol. The neural and neuroendocrine circuitry responsible for mammalian seasonal reproduction has been primarily studied in three animal models: the sheep, and two species of hamsters. In this review, we first describe the afferent signals, neural circuitry and transmitters/peptides responsible for seasonal reproductive transitions in sheep, and then compare these mechanisms with those derived from studies in hamsters. The results suggest common principles as well as differences in the role of specific brain nuclei and neuropeptides, including that of kisspeptin cells of the hypothalamic arcuate nucleus, in regulating seasonal reproduction among mammals. PMID:25582913

  2. Neural Networks

    Directory of Open Access Journals (Sweden)

    Schwindling Jerome

    2010-04-01

    Full Text Available This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p. corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

  3. Neural correlates of the formation and retention of cocaine-induced stimulus-reward associations

    OpenAIRE

    Nelissen, Koen; Jarraya, Bechir; Arsenault, John; Rosen, Bruce; Wald, Lawrence,; Mandeville, Joseph; Marota, John; Vanduffel, Wim

    2012-01-01

    Background: Cocaine can elicit drug-seeking behavior for drug-predicting stimuli, even after a single stimulus-cocaine pairing. While orbitofrontal cortex is thought to be important during encoding and maintenance of stimulus-reward value, we still lack a comprehensive model of the neural circuitry underlying this cognitive process. Methods: We studied the conditioned effects of cocaine using monkey fMRI and classical conditioning by pairing a visual shape (conditioning stimulus, CS+) wit...

  4. Matched Behavioral and Neural Adaptations for Low Sound Level Echolocation in a Gleaning Bat, Antrozous pallidus

    OpenAIRE

    Measor, Kevin R.; Leavell, Brian C.; Brewton, Dustin H.; Rumschlag, Jeffrey; Barber, Jesse R.; Razak, Khaleel A.

    2017-01-01

    Abstract In active sensing, animals make motor adjustments to match sensory inputs to specialized neural circuitry. Here, we describe an active sensing system for sound level processing. The pallid bat uses downward frequency-modulated (FM) sweeps as echolocation calls for general orientation and obstacle avoidance. The bat?s auditory cortex contains a region selective for these FM sweeps (FM sweep-selective region, FMSR). We show that the vast majority of FMSR neurons are sensitive and stron...

  5. Sequence tolerance of the phage lambda PRM promoter: implications for evolution of gene regulatory circuitry.

    Science.gov (United States)

    Michalowski, Christine B; Short, Megan D; Little, John W

    2004-12-01

    Much of the gene regulatory circuitry of phage lambda centers on a complex region called the O(R) region. This approximately 100-bp region is densely packed with regulatory sites, including two promoters and three repressor-binding sites. The dense packing of this region is likely to impose severe constraints on its ability to change during evolution, raising the question of how the specific arrangement of sites and their exact sequences could evolve to their present form. Here we ask whether the sequence of a cis-acting site can be widely varied while retaining its function; if it can, evolution could proceed by a larger number of paths. To help address this question, we developed a lambda cloning vector that allowed us to clone fragments spanning the O(R) region. By using this vector, we carried out intensive mutagenesis of the P(RM) promoter, which drives expression of CI repressor and is activated by CI itself. We made a pool of fragments in which 8 of the 12 positions in the -35 and -10 regions were randomized and cloned this pool into the vector, making a pool of P(RM) variant phage. About 10% of the P(RM) variants were able to lysogenize, suggesting that the lambda regulatory circuitry is compatible with a wide range of P(RM) sequences. Analysis of several of these phages indicated a range of behaviors in prophage induction. Several isolates had induction properties similar to those of the wild type, and their promoters resembled the wild type in their responses to CI. We term this property of different sequences allowing roughly equivalent function "sequence tolerance " and discuss its role in the evolution of gene regulatory circuitry.

  6. Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry.

    Science.gov (United States)

    Navratilova, Edita; Xie, Jennifer Y; Okun, Alec; Qu, Chaoling; Eyde, Nathan; Ci, Shuang; Ossipov, Michael H; King, Tamara; Fields, Howard L; Porreca, Frank

    2012-12-11

    Relief of pain is rewarding. Using a model of experimental postsurgical pain we show that blockade of afferent input from the injury with local anesthetic elicits conditioned place preference, activates ventral tegmental dopaminergic cells, and increases dopamine release in the nucleus accumbens. Importantly, place preference is associated with increased activity in midbrain dopaminergic neurons and blocked by dopamine antagonists injected into the nucleus accumbens. The data directly support the hypothesis that relief of pain produces negative reinforcement through activation of the mesolimbic reward-valuation circuitry.

  7. Fabrication and Measurement of a Suspended Nanochannel Microbridge Resonator Monolithically Integrated with CMOS Readout Circuitry

    Directory of Open Access Journals (Sweden)

    Gabriel Vidal-Álvarez

    2016-03-01

    Full Text Available We present the fabrication and characterization of a suspended microbridge resonator with an embedded nanochannel. The suspended microbridge resonator is electrostatically actuated, capacitively sensed, and monolithically integrated with complementary metal-oxide-semiconductor (CMOS readout circuitry. The device is fabricated using the back end of line (BEOL layers of the AMS 0.35 μm commercial CMOS technology, interconnecting two metal layers with a contact layer. The fabricated device has a 6 fL capacity and has one of the smallest embedded channels so far. It is able to attain a mass sensitivity of 25 ag/Hz using a fully integrable electrical transduction.

  8. Neural bases of accented speech perception

    OpenAIRE

    Patti eAdank; Nuttall, Helen E.; Briony eBanks; Dan eKennedy-Higgins

    2015-01-01

    The recognition of unfamiliar regional and foreign accents represents a challenging task for the speech perception system (Adank, Evans, Stuart-Smith, & Scott, 2009; Floccia, Goslin, Girard, & Konopczynski, 2006). Despite the frequency with which we encounter such accents, the neural mechanisms supporting successful perception of accented speech are poorly understood. Nonetheless, candidate neural substrates involved in processing speech in challenging listening conditions, including accented...

  9. A dynamical systems view of motor preparation: Implications for neural prosthetic system design

    Science.gov (United States)

    Shenoy, Krishna V.; Kaufman, Matthew T.; Sahani, Maneesh; Churchland, Mark M.

    2013-01-01

    Neural prosthetic systems aim to help disabled patients suffering from a range of neurological injuries and disease by using neural activity from the brain to directly control assistive devices. This approach in effect bypasses the dysfunctional neural circuitry, such as an injured spinal cord. To do so, neural prostheses depend critically on a scientific understanding of the neural activity that drives them. We review here several recent studies aimed at understanding the neural processes in premotor cortex that precede arm movements and lead to the initiation of movement. These studies were motivated by hypotheses and predictions conceived of within a dynamical systems perspective. This perspective concentrates on describing the neural state using as few degrees of freedom as possible and on inferring the rules that govern the motion of that neural state. Although quite general, this perspective has led to a number of specific predictions that have been addressed experimentally. It is hoped that the resulting picture of the dynamical role of preparatory and movement-related neural activity will be particularly helpful to the development of neural prostheses, which can themselves be viewed as dynamical systems under the control of the larger dynamical system to which they are attached. PMID:21763517

  10. [Neural activity related to emotional and empathic deficits in subjects with post-traumatic stress disorder who survived the L'Aquila (Central Italy) 2009 earthquake].

    Science.gov (United States)

    Mazza, Monica; Pino, Maria Chiara; Tempesta, Daniela; Catalucci, Alessia; Masciocchi, Carlo; Ferrara, Michele

    2016-01-01

    Post-Traumatic Stress Disorder (PTSD) is a chronic anxiety disorder. The continued efforts to control the distressing memories by traumatized individuals, together with the reduction of responsiveness to the outside world, are called Emotional Numbing (EN). The EN is one of the central symptoms in PTSD and it plays an integral role not only in the development and maintenance of post-traumatic symptomatology, but also in the disability of emotional regulation. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. Patients with PTSD exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional and empathic dysfunction. We showed that PTSD patients, all survivors of the L'Aquila 2009 earthquake, have a higher sensitivity to negative emotion and lower empathy levels. These emotional and empathic deficits are accompanied by neural brain functional correlates. Indeed PTSD subjects exhibit functional abnormalities in brain regions that are involved in stress regulation and emotional responses. The reduced activation of the frontal areas and a stronger activation of the limbic areas when responding to emotional stimuli could lead the subjects to enact coping strategies aimed at protecting themselves from the re-experience of pain related to traumatic events. This would result in a dysfunctional hyperactivation of subcortical areas, which may cause emotional distress and, consequently, impaired social relationships often reported by PTSD patients.

  11. Games in the Brain: Neural Substrates of Gambling Addiction.

    Science.gov (United States)

    Murch, W Spencer; Clark, Luke

    2016-10-01

    As a popular form of recreational risk taking, gambling games offer a paradigm for decision neuroscience research. As an individual behavior, gambling becomes dysfunctional in a subset of the population, with debilitating consequences. Gambling disorder has been recently reconceptualized as a "behavioral addiction" in the DSM-5, based on emerging parallels with substance use disorders. Why do some individuals undergo this transition from recreational to disordered gambling? The biomedical model of problem gambling is a "brain disorder" account that posits an underlying neurobiological abnormality. This article first delineates the neural circuitry that underpins gambling-related decision making, comprising ventral striatum, ventromedial prefrontal cortex, dopaminergic midbrain, and insula, and presents evidence for pathophysiology in this circuitry in gambling disorder. These biological dispositions become translated into clinical disorder through the effects of gambling games. This influence is better articulated in a public health approach that describes the interplay between the player and the (gambling) product. Certain forms of gambling, including electronic gambling machines, appear to be overrepresented in problem gamblers. These games harness psychological features, including variable ratio schedules, near-misses, "losses disguised as wins," and the illusion of control, which modulate the core decision-making circuitry that is perturbed in gambling disorder. © The Author(s) 2015.

  12. Neural mechanisms underlying changes in stress-sensitivity across the menstrual cycle.

    Science.gov (United States)

    Ossewaarde, Lindsey; Hermans, Erno J; van Wingen, Guido A; Kooijman, Sabine C; Johansson, Inga-Maj; Bäckström, Torbjörn; Fernández, Guillén

    2010-01-01

    Hormonal fluctuations across the menstrual cycle are thought to play a central role in premenstrual mood symptoms. In agreement, fluctuations in gonadal hormone levels affect brain processes in regions involved in emotion regulation. Recent findings, however, implicate psychological stress as a potential mediating factor and thus, we investigated whether effects of moderate psychological stress on relevant brain regions interact with menstrual cycle phase. Twenty-eight healthy women were tested in a crossover design with menstrual cycle phase (late luteal versus late follicular) and stress (stress induction versus control) as within-subject factors. After stress induction (or control), we probed neural responses to facial expressions using fMRI. During the late luteal phase, negative affect was highest and the stress-induced increase in heart rate was mildly augmented. fMRI data of the control condition replicate previous findings of elevated amygdala and medial prefrontal cortex responses when comparing the late luteal with the late follicular phase. Importantly, stress induction had opposite effects in the two cycle phases, with unexpected lower response magnitudes in the late luteal phase. Moreover, the larger the increase in allopregnanolone concentration across the menstrual cycle was, the smaller the amygdala and medial prefrontal cortex responses were after stress induction in the late luteal phase. Our findings show that moderate psychological stress influences menstrual cycle effects on activity in the emotion regulation circuitry. These results provide potential insights into how fluctuations in allopregnanolone that naturally occur during the menstrual cycle may change stress vulnerability.

  13. Neural network based system for equipment surveillance

    Science.gov (United States)

    Vilim, R.B.; Gross, K.C.; Wegerich, S.W.

    1998-04-28

    A method and system are disclosed for performing surveillance of transient signals of an industrial device to ascertain the operating state. The method and system involves the steps of reading into a memory training data, determining neural network weighting values until achieving target outputs close to the neural network output. If the target outputs are inadequate, wavelet parameters are determined to yield neural network outputs close to the desired set of target outputs and then providing signals characteristic of an industrial process and comparing the neural network output to the industrial process signals to evaluate the operating state of the industrial process. 33 figs.

  14. The Contributions of Cerebro-Cerebellar Circuitry to Executive Verbal Working Memory

    Science.gov (United States)

    Marvel, Cherie L.; Desmond, John E.

    2009-01-01

    Contributions of cerebro-cerebellar function to executive verbal working memory were examined using event-related functional magnetic resonance imaging (fMRI) while 16 subjects completed two versions of the Sternberg task. In both versions subjects were presented with two or six target letters during the encoding phase, which were held in memory during the maintenance phase. A single probe letter was presented during the retrieval phase. In the “match condition”, subjects decided whether the probe matched the target letters. In the “executive condition”, subjects created a new probe by counting two alphabetical letters forward (e.g., f → h) and decided whether the new probe matched the target letters. Neural activity during the match and executive conditions was compared during each phase of the task. There were four main findings. First, cerebro-cerebellar activity increased as a function of executive load. Second, the dorsal cerebellar dentate co-activated with the supplementary motor area (SMA) during encoding. This likely represented the formation of an articulatory (motor) trajectory. Third, the ventral cerebellar dentate co-activated with anterior prefrontal regions BA 9/46 and the pre-SMA during retrieval. This likely represented the manipulation of information and formation of a response. A functional dissociation between the dorsal “motor” dentate and “cognitive” ventral dentate agrees with neuroanatomical tract tracing studies that have demonstrated separate neural pathways involving each region of the dentate: the dorsal dentate projects to frontal motor areas (including the SMA), and the ventral dentate projects to frontal cognitive areas (including BA 9/46 and the pre-SMA). Finally, activity during the maintenance phase in BA 9, anterior insula, pre-SMA and ventral dentate predicted subsequent accuracy of response to the probe during the retrieval phase. This finding underscored the significant contribution of the pre

  15. Combined driving and sensing circuitry for dielectric elastomer actuators in mobile applications

    Science.gov (United States)

    Matysek, Marc; Haus, Henry; Moessinger, Holger; Brokken, Dirk; Lotz, Peter; Schlaak, Helmut F.

    2011-04-01

    Dielectric elastomer stack actuators (DESA) promise breakthrough functionality in user interfaces by enabling freely programmable surfaces with various shapes. Besides the fundamental advantages of this technology, like comparatively low energy consumption, it is well known that these actuators can be used as sensors simultaneously. The work we present in this paper is focused on the implementation of a DEA-based tactile display into a mobile device. The generation of the driving voltage of up to 1.1 kV out of a common rechargeable battery and the implementation of the sensor functionality are the most challenging tasks. To realize a large range of tactile experiences, both static and dynamic driving voltages are required. We present a structure combining different step-up topologies to realize the driving unit. The final circuitry complies with typical requirements for mobile devices, like small size, low weight, high efficiency and low costs. The sensing functionality has to be realized for different actuator elements regardless of their actual state. An additional sensing layer on top or within the actuators would cause a higher fabrication effort and additional interconnections. Therefore, we developed a high voltage compatible sensing system. The circuitry allows sensing of user input at every actuator element. Both circuits are implemented into a handheld-like device.

  16. A Wirelessly Powered Smart Contact Lens with Reconfigurable Wide Range and Tunable Sensitivity Sensor Readout Circuitry.

    Science.gov (United States)

    Chiou, Jin-Chern; Hsu, Shun-Hsi; Huang, Yu-Chieh; Yeh, Guan-Ting; Liou, Wei-Ting; Kuei, Cheng-Kai

    2017-01-07

    This study presented a wireless smart contact lens system that was composed of a reconfigurable capacitive sensor interface circuitry and wirelessly powered radio-frequency identification (RFID) addressable system for sensor control and data communication. In order to improve compliance and reduce user discomfort, a capacitive sensor was embedded on a soft contact lens of 200 μm thickness using commercially available bio-compatible lens material and a standard manufacturing process. The results indicated that the reconfigurable sensor interface achieved sensitivity and baseline tuning up to 120 pF while consuming only 110 μW power. The range and sensitivity tuning of the readout circuitry ensured a reliable operation with respect to sensor fabrication variations and independent calibration of the sensor baseline for individuals. The on-chip voltage scaling allowed the further extension of the detection range and prevented the implementation of large on-chip elements. The on-lens system enabled the detection of capacitive variation caused by pressure changes in the range of 2.25 to 30 mmHg and hydration level variation from a distance of 1 cm using incident power from an RFID reader at 26.5 dBm.

  17. Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Anne J Blood

    2010-11-01

    Full Text Available Previous studies of major depressive disorder (MDD have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN, and medial forebrain bundle (MFB.We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity.These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.

  18. Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence.

    Science.gov (United States)

    Herringa, Ryan J; Birn, Rasmus M; Ruttle, Paula L; Burghy, Cory A; Stodola, Diane E; Davidson, Richard J; Essex, Marilyn J

    2013-11-19

    Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus-subgenual cingulate rs-FC in both adolescent females and males and lower amygdala-subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain's fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto-hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto-amygdala and -hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.

  19. A CMOS IC–based multisite measuring system for stimulation and recording in neural preparations in vitro

    Directory of Open Access Journals (Sweden)

    Takashi eTateno

    2014-10-01

    Full Text Available In this report, we describe the system integration of a complementary metal oxide semiconductor (CMOS integrated circuit (IC chip, capable of both stimulation and recording of neurons or neural tissues, to investigate electrical signal propagation within cellular networks in vitro. The overall system consisted of three major subunits: a 5.0 mm × 5.0 mm CMOS IC chip, a reconfigurable logic device (field-programmable gate array, FPGA, and a PC. To test the system, microelectrode arrays (MEAs were used to extracellularly measure the activity of cultured rat cortical neurons and mouse cortical slices. The MEA had 64 bidirectional (stimulation and recording electrodes. In addition, the CMOS IC chip was equipped with dedicated analog filters, amplification stages, and a stimulation buffer. Signals from the electrodes were sampled at 15.6 kHz with 16-bit resolution. The measured input-referred circuitry noise was 10.1 μV root mean square (10 Hz to 100 kHz, which allowed reliable detection of neural signals ranging from several millivolts down to approximately 33 μVpp. Experiments were performed involving the stimulation of neurons with several spatiotemporal patterns and the recording of the triggered activity. An advantage over current MEAs, as demonstrated by our experiments, includes the ability to stimulate (voltage stimulation, 5-bit resolution spatiotemporal patterns in arbitrary subsets of electrodes. Furthermore, the fast stimulation reset mechanism allowed us to record neuronal signals from a stimulating electrode around 3 ms after stimulation. We demonstrate that the system can be directly applied to, for example, auditory neural prostheses in conjunction with an acoustic sensor and a sound processing system.

  20. Educating the blind brain: a panorama of neural bases of vision and of training programs in organic neurovisual deficits

    Directory of Open Access Journals (Sweden)

    Olivier A. Coubard

    2014-12-01

    Full Text Available Vision is a complex function, which is achieved by movements of the eyes to properly foveate targets at any location in 3D space and to continuously refresh neural information in the different visual pathways. The visual system involves five routes originating in the retinas but varying in their destination within the brain: the occipital cortex, but also the superior colliculus, the pretectum, the supra-chiasmatic nucleus, the nucleus of the optic tract and terminal dorsal, medial and lateral nuclei. Visual pathway architecture obeys systematization in sagittal and transversal planes so that visual information from left/right and upper/lower hemi-retinas, corresponding respectively to right/left and lower/upper visual fields, is processed ipsilaterally and ipsialtitudinally to hemi-retinas in left/right hemispheres and upper/lower fibers. Organic neurovisual deficits may occur at any level of this circuitry from the optic nerve to subcortical and cortical destinations, resulting in low or high-level visual deficits. In this didactic review article, we provide a panorama of the neural bases of eye movements and visual systems, and of related neurovisual deficits. Additionally, we briefly review the different schools of rehabilitation of organic neurovisual deficits, and show that whatever the emphasis is put on action or perception, benefits may be observed at both motor and perceptual levels. Given the extent of its neural bases in the brain, vision in its motor and perceptual aspects is also a useful tool to assess and modulate central nervous system in general.

  1. Neural Tube Defects

    Science.gov (United States)

    ... vitamin, before and during pregnancy prevents most neural tube defects. Neural tube defects are usually diagnosed before the infant is ... or imaging tests. There is no cure for neural tube defects. The nerve damage and loss of function ...

  2. Alcohol-induced dysregulation of stress-related circuitry: The search for novel targets and implications for interventions across the sexes.

    Science.gov (United States)

    Retson, T A; Sterling, R C; Van Bockstaele, E J

    2016-02-04

    While the ability to process fermented fruits and alcohols was once an adaptive trait that improved nutrition and quality of life, the availability and prevalence of high potency alcoholic drinks has contributed to alcohol abuse disorders in a vulnerable portion of the population. Although the neural reward systems take part in the initial response to alcohol, negative reinforcement and stress, which are normally adaptive responses, can intersect to promote continued alcohol use at all stages of the addiction cycle. Eventually a point is reached where these once adaptive responses become dysregulated resulting in uncontrolled intake that constitutes a clinically important condition termed alcohol use disorder (AUD). Current research is targeted at both the behavioral and molecular adaptations in AUDs in an effort to better develop novel approaches to intervention. In this review, historical context is provided demonstrating the societal burden of alcohol use and abuse disorders. The importance of gender in the mechanism of action of alcohol is discussed. Finally, the impact of alcohol on stress-related circuitry, uncovered by preclinical research, is outlined to provide insight into potential novel pharmacological approaches to the treatment of AUD. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Parametric study of dielectric loaded surface plasmon polariton add-drop filters for hybrid silicon/plasmonic optical circuitry

    Science.gov (United States)

    Dereux, A.; Hassan, K.; Weeber, J.-C.; Djellali, N.; Bozhevolnyi, S. I.; Tsilipakos, O.; Pitilakis, A.; Kriezis, E.; Papaioannou, S.; Vyrsokinos, K.; Pleros, N.; Tekin, T.; Baus, M.; Kalavrouziotis, D.; Giannoulis, G.; Avramopoulos, H.

    2011-01-01

    Surface plasmons polaritons are electromagnetic waves propagating along the surface of a conductor. Surface plasmons photonics is a promising candidate to satisfy the constraints of miniaturization of optical interconnects. This contribution reviews an experimental parametric study of dielectric loaded surface plasmon waveguides ring resonators and add-drop filters within the perspective of the recently suggested hybrid technology merging plasmonic and silicon photonics on a single board (European FP7 project PLATON "Merging Plasmonic and Silicon Photonics Technology towards Tb/s routing in optical interconnects"). Conclusions relevant for dielectric loaded surface plasmon switches to be integrated in silicon photonic circuitry will be drawn. They rely on the opportunity offered by plasmonic circuitry to carry optical signals and electric currents through the same thin metal circuitry. The heating of the dielectric loading by the electric current enables to design low foot-print thermo-optical switches driving the optical signal flow.

  4. Electro-active sensor, method for constructing the same; apparatus and circuitry for detection of electro-active species

    Science.gov (United States)

    Buehler, Martin (Inventor)

    2009-01-01

    An electro-active sensor includes a nonconductive platform with a first electrode set attached with a first side of a nonconductive platform. The first electrode set serves as an electrochemical cell that may be utilized to detect electro-active species in solution. A plurality of electrode sets and a variety of additional electrochemical cells and sensors may be attached with the nonconductive platform. The present invention also includes a method for constructing the aforementioned electro-active sensor. Additionally, an apparatus for detection and observation is disclosed, where the apparatus includes a sealable chamber for insertion of a portion of an electro-active sensor. The apparatus allows for monitoring and detection activities. Allowing for control of attached cells and sensors, a dual-mode circuitry is also disclosed. The dual-mode circuitry includes a switch, allowing the circuitry to be switched from a potentiostat to a galvanostat mode.

  5. Effects of co-administration of ketamine and ethanol on the dopamine system via the cortex-striatum circuitry.

    Science.gov (United States)

    Liu, Qing; Xu, Tian-Yong; Zhang, Zhi-Bi; Leung, Chi-Kwan; You, Ding-Yun; Wang, Shang-Wen; Yi, Shuai; Jing, Qiang; Xie, Run-Fang; Li, Huifang-Jie; Zeng, Xiao-Feng

    2017-06-15

    Ketamine and ethanol are increasingly being used together as recreational drugs in rave parties. Their effects on the dopamine (DA) system remain largely unknown. This study aimed to investigate the effects of consuming two different concentrations of ketamine with and without alcohol on the DA system. We employed the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of the combined administration of two different doses of ketamine (30mg/kg and 60mg/kg) with ethanol (0.3156g/kg). We evaluated the effects of the combined drug treatment on the transcriptional output of tyrosine hydroxylase (TH), dopa decarboxylase (DDC), synaptosomal-associated protein 25 (SNAP25), and vesicular monoamine transporter 2 (VMAT2) as well as protein expression level of brain-derived neurotrophic factor (BDNF) in rat prefrontal cortex (PFC) and striatum. We found that rats exhibited a dose-dependent, drug-paired, place preference to ketamine and ethanol associated with an elevated DA level in the striatum but not in the PFC. Moreover, treatment involving low- or high-dose ketamine with or without ethanol caused a differential regulatory response in the mRNA levels of the four DA metabolism genes and the cellular protein abundance of BDNF via the cortex-striatum circuitry. This study investigated the molecular mechanisms that occur following the combined administration of ketamine and ethanol in the DA system, which could potentially lead to alterations in the mental status and behavior of ketamine/ethanol users. Our findings may aid the development of therapeutic strategies for substance abuse patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Evolution of the human fear-circuitry and acute sociogenic pseudoneurological symptoms: the Neolithic balanced-polymorphism hypothesis.

    Science.gov (United States)

    Bracha, H Stefan; Yoshioka, Dawn T; Masukawa, Nicole K; Stockman, Deborah J J

    2005-10-01

    In light of the increasing threat of large-scale massacres such as terrorism against non-combatants (civilians), more attention is warranted not only to posttraumatic stress disorder (PTSD) but also to acute sociogenic pseudoneurological ("conversion") symptoms, especially epidemic sociogenic symptoms. We posit that conversion disorders are etiologically related to specific evolutionary pressures (inescapable threats to life) in the late stage of the human environment of evolutionary adaptedness (EEA). Bracha et al. have recently argued that from the neuroevolutionary perspective, medically unexplained efferent vasovagal syncope and medically unexplained craniofacial musculoskeletal pain in young otherwise healthy individuals, may be taxonomized as stress and fear-circuitry disorders. In the present article, we extend neuroevolutionary perspectives to acute pseudoneurological sociogenic ("conversive") symptoms: psychogenic non-epileptic attacks ("pseudoseizures"), epidemic sociogenic disorders (DSM-IV-TR Epidemic "Hysteria"), conversive motor deficits (pseudo-paralysis and pseudo-cerebellar symptoms), and psychogenic blindness. We hypothesize that these perplexing pseudoneurological stress-triggered symptoms, which constitute psychopathology in extant humans, are traceable to allele-variant polymorphisms which spread during the Neolithic EEA. During Neolithic warfare, conversive symptoms may have increased the survival odds for some non-combatants by visually (i.e., "non-verbally") signaling to predatory conspecifics that one does not present a danger. This is consistent with the age and sex pattern of conversive disorders. Testable and falsifiable predictions are presented; e.g., at the genome-transcriptome interface, one of the major oligogenic loci involved in conversive spectrum disorders may carry a developmentally sensitive allele in a stable polymorphism (balanced polymorphism) in which the gene expression mechanism is gradually suppressed by pleiotropic

  7. A fine coal circuitry study using column flotation and gravity separation. Technical report, September 1--November 30, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Honaker, R.Q. [Southern Illinois Univ., Carbondale, IL (United States). Dept. of Mining Engineering; Reed, S. [Kerr-McGee Coal Corp., Oklahoma City, OK (United States)

    1994-12-31

    Column flotation provides excellent recovery of ultrafine coal while producing low ash content concentrates. However, column flotation is not efficient for treating fine coal containing significant amounts of mixed-phase particles. Fortunately, enhanced gravity separation has proved to have the ability to treat the mixed-phased particles more effectively. A disadvantage of gravity separation is that ultrafine clay particles are not easily rejected. Thus, a combination of these two technologies may provide a circuit that maximizes both the ash and sulfur rejection that can be achieved by physical coal cleaning while maintaining a high energy recovery. This project is studying the potential of using different combinations of gravity separators, i.e., a Floatex hydrosizer and a Falcon Concentrator, and a proven flotation column, which will be selected based on previous studies by the principle investigator. The gravity/flotation circuits will be compared based on their optimum separation performance which will consider ash and total sulfur rejection and energy recovery as well as the probable error (E{sub p}) value obtained from washability analyses. During this reporting period, multi-stage treatment using the Falcon concentrator was conducted on a refuse pond ({minus}100 mesh) coal sample and a {minus}28 mesh run-of-mine coal sample. The results suggest that the Falcon concentrator can make an ideal separation for either sample in a single process. Recleaning was found to improve product grade, however, recovery was reduced sharply. In addition, the groups involved with the in-plant testing of the Floatex Hydrosizer met and organized the test plan which will be conducted at Kerr-McGee`s Galatia preparation plant during the next reporting period. Coal samples for the circuitry tests will be collected during, this time period.

  8. Endocannabinoids and liver disease. IV. Endocannabinoid involvement in obesity and hepatic steatosis.

    Science.gov (United States)

    Kunos, George; Osei-Hyiaman, Douglas

    2008-05-01

    Endocannabinoids are endogenous lipid mediators that interact with the same receptors as plant-derived cannabinoids to produce similar biological effects. The well-known appetitive effect of smoking marijuana has prompted inquiries into the possible role of endocannabinoids in the control of food intake and body weight. This brief review surveys recent evidence that endocannabinoids and their receptors are involved at multiple levels in the control of energy homeostasis. Endocannabinoids are orexigenic mediators and are part of the leptin-regulated central neural circuitry that controls energy intake. In addition, they act at multiple peripheral sites including adipose tissue, liver, and skeletal muscle to promote lipogenesis and limit fat elimination. Their complex actions could be viewed as anabolic, increasing energy intake and storage and decreasing energy expenditure, as components of an evolutionarily conserved system that has insured survival under conditions of starvation. In the era of plentiful food and limited physical activity, pharmacological inhibition of endocannabinoid activity offers benefits in the treatment of obesity and its hormonal/metabolic consequences.

  9. [Neural repair].

    Science.gov (United States)

    Kitada, Masaaki; Dezawa, Mari

    2008-05-01

    Recent progress of stem cell biology gives us the hope for neural repair. We have established methods to specifically induce functional Schwann cells and neurons from bone marrow stromal cells (MSCs). The effectiveness of these induced cells was evaluated by grafting them either into peripheral nerve injury, spinal cord injury, or Parkinson' s disease animal models. MSCs-derived Schwann cells supported axonal regeneration and re-constructed myelin to facilitate the functional recovery in peripheral and spinal cord injury. MSCs-derived dopaminergic neurons integrated into host striatum and contributed to behavioral repair. In this review, we introduce the differentiation potential of MSCs and finally discuss about their benefits and drawbacks of these induction systems for cell-based therapy in neuro-traumatic and neuro-degenerative diseases.

  10. Exercise-enhanced Neuroplasticity Targeting Motor and Cognitive Circuitry in Parkinson’s Disease

    Science.gov (United States)

    Petzinger, G. M.; Fisher, B. E.; McEwen, S.; Beeler, J. A.; Walsh, J. P.; Jakowec, M. W.

    2013-01-01

    The purpose of this review is to highlight the potential role of exercise in promoting neuroplasticity and repair in Parkinson’s disease (PD). Exercise interventions in individuals with PD incorporate goal-based motor skill training in order to engage cognitive circuitry important in motor learning. Using this exercise approach, physical therapy facilitates learning through instruction and feedback (reinforcement), and encouragement to perform beyond self-perceived capability. Individuals with PD become more cognitively engaged with the practice and learning of movements and skills that were previously automatic and unconscious. Studies that have incorporated both goal-based training and aerobic exercise have supported the potential for improving both cognitive and automatic components of motor control. Utilizing animal models, basic research is beginning to reveal exercise-induced effects on neuroplasticity. Since neuroplasticity occurs at the level of circuits and synaptic connections, we examine the effects of exercise from this perspective. PMID:23769598

  11. Exploiting the dynamic properties of covalent modification cycle for the design of synthetic analog biomolecular circuitry.

    Science.gov (United States)

    Foo, Mathias; Sawlekar, Rucha; Bates, Declan G

    2016-01-01

    Cycles of covalent modification are ubiquitous motifs in cellular signalling. Although such signalling cycles are implemented via a highly concise set of chemical reactions, they have been shown to be capable of producing multiple distinct input-output mapping behaviours - ultrasensitive, hyperbolic, signal-transducing and threshold-hyperbolic. In this paper, we show how the set of chemical reactions underlying covalent modification cycles can be exploited for the design of synthetic analog biomolecular circuitry. We show that biomolecular circuits based on the dynamics of covalent modification cycles allow (a) the computation of nonlinear operators using far fewer chemical reactions than purely abstract designs based on chemical reaction network theory, and (b) the design of nonlinear feedback controllers with strong performance and robustness properties. Our designs provide a more efficient route for translation of complex circuits and systems from chemical reactions to DNA strand displacement-based chemistry, thus facilitating their experimental implementation in future Synthetic Biology applications.

  12. Speech and music quality ratings for linear and nonlinear hearing aid circuitry.

    Science.gov (United States)

    Davies-Venn, Evelyn; Souza, Pamela; Fabry, David

    2007-09-01

    This study evaluated quality ratings for speech and music stimuli processed using peak clipping (PC), compression limiting (CL), and wide-dynamic range compression (WDRC) hearing aid circuitry. Eighteen listeners with mild-to-moderate hearing loss were binaurally fitted with behind-the-ear (BTE) hearing aids and instructed to rate the quality of speech under various conditions in quiet and noise and two genres of music. Results for speech revealed a slight preference for WDRC at 80 dB SPL, and equivalent ratings for the three circuits under all other listening conditions. Music ratings revealed a marginally significant preference for WDRC and a preference for classical over popular music. For music, judgments on pleasantness were the most influential on overall circuit preference.

  13. Understanding the Molecular Circuitry of Cell Lineage Specification in the Early Mouse Embryo

    Science.gov (United States)

    Bergsmedh, Anna; Donohoe, Mary E.; Hughes, Rebecca-Ayme; Hadjantonakis, Anna-Katerina

    2011-01-01

    Pluripotent stem cells hold great promise for cell-based therapies in regenerative medicine. However, critical to understanding and exploiting mechanisms of cell lineage specification, epigenetic reprogramming, and the optimal environment for maintaining and differentiating pluripotent stem cells is a fundamental knowledge of how these events occur in normal embryogenesis. The early mouse embryo has provided an excellent model to interrogate events crucial in cell lineage commitment and plasticity, as well as for embryo-derived lineage-specific stem cells and induced pluripotent stem (iPS) cells. Here we provide an overview of cell lineage specification in the early (preimplantation) mouse embryo focusing on the transcriptional circuitry and epigenetic marks necessary for successive differentiation events leading to the formation of the blastocyst. PMID:24710206

  14. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation

    Science.gov (United States)

    Li, Jiang; Green, Alexander A.; Yan, Hao; Fan, Chunhai

    2017-11-01

    Nucleic acids have attracted widespread attention due to the simplicity with which they can be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of DNA/RNA nanotechnology offer numerous opportunities for in-cell and in-vivo applications, and the technology holds great promise to advance the growing field of synthetic biology. Many elegant examples have revealed the potential in integrating nucleic acid nanostructures in cells and in vivo where they can perform important physiological functions. In this Review, we summarize the current abilities of DNA/RNA nanotechnology to realize applications in live cells and then discuss the key problems that must be solved to fully exploit the useful properties of nanostructures. Finally, we provide viewpoints on how to integrate the tools provided by DNA/RNA nanotechnology and related new technologies to construct nucleic acid nanostructure-based molecular circuitry for synthetic biology.

  15. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Science.gov (United States)

    Polvi, Elizabeth J; Averette, Anna F; Lee, Soo Chan; Kim, Taeyup; Bahn, Yong-Sun; Veri, Amanda O; Robbins, Nicole; Heitman, Joseph; Cowen, Leah E

    2016-10-01

    Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation

  16. Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Polvi

    2016-10-01

    Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

  17. Neural Mechanisms of Circadian Regulation of Natural and Drug Reward

    Directory of Open Access Journals (Sweden)

    Lauren M. DePoy

    2017-01-01

    Full Text Available Circadian rhythms are endogenously generated near 24-hour variations of physiological and behavioral functions. In humans, disruptions to the circadian system are associated with negative health outcomes, including metabolic, immune, and psychiatric diseases, such as addiction. Animal models suggest bidirectional relationships between the circadian system and drugs of abuse, whereby desynchrony, misalignment, or disruption may promote vulnerability to drug use and the transition to addiction, while exposure to drugs of abuse may entrain, disrupt, or perturb the circadian timing system. Recent evidence suggests natural (i.e., food and drug rewards may influence overlapping neural circuitry, and the circadian system may modulate the physiological and behavioral responses to these stimuli. Environmental disruptions, such as shifting schedules or shorter/longer days, influence food and drug intake, and certain mutations of circadian genes that control cellular rhythms are associated with altered behavioral reward. We highlight the more recent findings associating circadian rhythms to reward function, linking environmental and genetic evidence to natural and drug reward and related neural circuitry.

  18. Neural substrates of approach-avoidance conflict decision-making.

    Science.gov (United States)

    Aupperle, Robin L; Melrose, Andrew J; Francisco, Alex; Paulus, Martin P; Stein, Murray B

    2015-02-01

    Animal approach-avoidance conflict paradigms have been used extensively to operationalize anxiety, quantify the effects of anxiolytic agents, and probe the neural basis of fear and anxiety. Results from human neuroimaging studies support that a frontal-striatal-amygdala neural circuitry is important for approach-avoidance learning. However, the neural basis of decision-making is much less clear in this context. Thus, we combined a recently developed human approach-avoidance paradigm with functional magnetic resonance imaging (fMRI) to identify neural substrates underlying approach-avoidance conflict decision-making. Fifteen healthy adults completed the approach-avoidance conflict (AAC) paradigm during fMRI. Analyses of variance were used to compare conflict to nonconflict (avoid-threat and approach-reward) conditions and to compare level of reward points offered during the decision phase. Trial-by-trial amplitude modulation analyses were used to delineate brain areas underlying decision-making in the context of approach/avoidance behavior. Conflict trials as compared to the nonconflict trials elicited greater activation within bilateral anterior cingulate cortex, anterior insula, and caudate, as well as right dorsolateral prefrontal cortex (PFC). Right caudate and lateral PFC activation was modulated by level of reward offered. Individuals who showed greater caudate activation exhibited less approach behavior. On a trial-by-trial basis, greater right lateral PFC activation related to less approach behavior. Taken together, results suggest that the degree of activation within prefrontal-striatal-insula circuitry determines the degree of approach versus avoidance decision-making. Moreover, the degree of caudate and lateral PFC activation related to individual differences in approach-avoidance decision-making. Therefore, the approach-avoidance conflict paradigm is ideally suited to probe anxiety-related processing differences during approach-avoidance decision

  19. Neural network optimization, components, and design selection

    Science.gov (United States)

    Weller, Scott W.

    1991-01-01

    Neural Networks are part of a revived technology which has received a lot of hype in recent years. As is apt to happen in any hyped technology, jargon and predictions make its assimilation and application difficult. Nevertheless, Neural Networks have found use in a number of areas, working on non-trivial and non-contrived problems. For example, one net has been trained to "read", translating English text into phoneme sequences. Other applications of Neural Networks include data base manipulation and the solving of routing and classification types of optimization problems. It was their use in optimization that got me involved with Neural Networks. As it turned out, "optimization" used in this context was somewhat misleading, because while some network configurations could indeed solve certain kinds of optimization problems, the configuring or "training" of a Neural Network itself is an optimization problem, and most of the literature which talked about Neural Nets and optimization in the same breath did not speak to my goal of using Neural Nets to help solve lens optimization problems. I did eventually apply Neural Network to lens optimization, and I will touch on those results. The application of Neural Nets to the problem of lens selection was much more successful, and those results will dominate this paper.

  20. The Neural Crest in Cardiac Congenital Anomalies

    Science.gov (United States)

    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

  1. Trace Eyeblink Conditioning in Mice Is Dependent upon the Dorsal Medial Prefrontal Cortex, Cerebellum, and Amygdala: Behavioral Characterization and Functional Circuitry(1,2,3).

    Science.gov (United States)

    Siegel, Jennifer J; Taylor, William; Gray, Richard; Kalmbach, Brian; Zemelman, Boris V; Desai, Niraj S; Johnston, Daniel; Chitwood, Raymond A

    2015-01-01

    Trace eyeblink conditioning is useful for studying the interaction of multiple brain areas in learning and memory. The goal of the current work was to determine whether trace eyeblink conditioning could be established in a mouse model in the absence of elicited startle responses and the brain circuitry that supports this learning. We show here that mice can acquire trace conditioned responses (tCRs) devoid of startle while head-restrained and permitted to freely run on a wheel. Most mice (75%) could learn with a trace interval of 250 ms. Because tCRs were not contaminated with startle-associated components, we were able to document the development and timing of tCRs in mice, as well as their long-term retention (at 7 and 14 d) and flexible expression (extinction and reacquisition). To identify the circuitry involved, we made restricted lesions of the medial prefrontal cortex (mPFC) and found that learning was prevented. Furthermore, inactivation of the cerebellum with muscimol completely abolished tCRs, demonstrating that learned responses were driven by the cerebellum. Finally, inactivation of the mPFC and amygdala in trained animals nearly abolished tCRs. Anatomical data from these critical regions showed that mPFC and amygdala both project to the rostral basilar pons and overlap with eyelid-associated pontocerebellar neurons. The data provide the first report of trace eyeblink conditioning in mice in which tCRs were driven by the cerebellum and required a localized region of mPFC for acquisition. The data further reveal a specific role for the amygdala as providing a conditioned stimulus-associated input to the cerebellum.

  2. Trace Eyeblink Conditioning in Mice Is Dependent upon the Dorsal Medial Prefrontal Cortex, Cerebellum, and Amygdala: Behavioral Characterization and Functional Circuitry1,2,3

    Science.gov (United States)

    Taylor, William; Gray, Richard; Kalmbach, Brian; Zemelman, Boris V.; Desai, Niraj S.; Johnston, Daniel; Chitwood, Raymond A.

    2015-01-01

    Abstract Trace eyeblink conditioning is useful for studying the interaction of multiple brain areas in learning and memory. The goal of the current work was to determine whether trace eyeblink conditioning could be established in a mouse model in the absence of elicited startle responses and the brain circuitry that supports this learning. We show here that mice can acquire trace conditioned responses (tCRs) devoid of startle while head-restrained and permitted to freely run on a wheel. Most mice (75%) could learn with a trace interval of 250 ms. Because tCRs were not contaminated with startle-associated components, we were able to document the development and timing of tCRs in mice, as well as their long-term retention (at 7 and 14 d) and flexible expression (extinction and reacquisition). To identify the circuitry involved, we made restricted lesions of the medial prefrontal cortex (mPFC) and found that learning was prevented. Furthermore, inactivation of the cerebellum with muscimol completely abolished tCRs, demonstrating that learned responses were driven by the cerebellum. Finally, inactivation of the mPFC and amygdala in trained animals nearly abolished tCRs. Anatomical data from these critical regions showed that mPFC and amygdala both project to the rostral basilar pons and overlap with eyelid-associated pontocerebellar neurons. The data provide the first report of trace eyeblink conditioning in mice in which tCRs were driven by the cerebellum and required a localized region of mPFC for acquisition. The data further reveal a specific role for the amygdala as providing a conditioned stimulus-associated input to the cerebellum. PMID:26464998

  3. Neural crest contributions to the lamprey head

    Science.gov (United States)

    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

    The neural crest is a vertebrate-specific cell population that contributes to the facial skeleton and other derivatives. We have performed focal DiI injection into the cranial neural tube of the developing lamprey in order to follow the migratory pathways of discrete groups of cells from origin to destination and to compare neural crest migratory pathways in a basal vertebrate to those of gnathostomes. The results show that the general pathways of cranial neural crest migration are conserved throughout the vertebrates, with cells migrating in streams analogous to the mandibular and hyoid streams. Caudal branchial neural crest cells migrate ventrally as a sheet of cells from the hindbrain and super-pharyngeal region of the neural tube and form a cylinder surrounding a core of mesoderm in each pharyngeal arch, similar to that seen in zebrafish and axolotl. In addition to these similarities, we also uncovered important differences. Migration into the presumptive caudal branchial arches of the lamprey involves both rostral and caudal movements of neural crest cells that have not been described in gnathostomes, suggesting that barriers that constrain rostrocaudal movement of cranial neural crest cells may have arisen after the agnathan/gnathostome split. Accordingly, neural crest cells from a single axial level contributed to multiple arches and there was extensive mixing between populations. There was no apparent filling of neural crest derivatives in a ventral-to-dorsal order, as has been observed in higher vertebrates, nor did we find evidence of a neural crest contribution to cranial sensory ganglia. These results suggest that migratory constraints and additional neural crest derivatives arose later in gnathostome evolution.

  4. CHARACTERIZATION OF OZONE EMISSIONS FROM AIR CLEANERS EQUIPPED WITH OZONE GENERATORS AND SENSOR AND FEEDBACK CONTROL CIRCUITRY

    Science.gov (United States)

    The paper give results of a characterization of ozone emissions from air cleaners equipped with ozone generators and sensor and feedback control circuitry. Ozone emission rates of several consumer appliances, marketed as indoor air treatment or air purification systems, were det...

  5. A physiological neural controller of a muscle fiber oculomotor plant in horizontal monkey saccades.

    Science.gov (United States)

    Ghahari, Alireza; Enderle, John D

    2014-01-01

    A neural network model of biophysical neurons in the midbrain is presented to drive a muscle fiber oculomotor plant during horizontal monkey saccades. Neural circuitry, including omnipause neuron, premotor excitatory and inhibitory burst neurons, long lead burst neuron, tonic neuron, interneuron, abducens nucleus, and oculomotor nucleus, is developed to examine saccade dynamics. The time-optimal control strategy by realization of agonist and antagonist controller models is investigated. In consequence, each agonist muscle fiber is stimulated by an agonist neuron, while an antagonist muscle fiber is unstimulated by a pause and step from the antagonist neuron. It is concluded that the neural network is constrained by a minimum duration of the agonist pulse and that the most dominant factor in determining the saccade magnitude is the number of active neurons for the small saccades. For the large saccades, however, the duration of agonist burst firing significantly affects the control of saccades. The proposed saccadic circuitry establishes a complete model of saccade generation since it not only includes the neural circuits at both the premotor and motor stages of the saccade generator, but also uses a time-optimal controller to yield the desired saccade magnitude.

  6. Neural scaling laws for an uncertain world

    CERN Document Server

    Howard, Marc W

    2016-01-01

    The Weber-Fechner law describes the form of psychological space in many behavioral experiments involving perception of one-dimensional physical quantities. If the physical quantity is expressed using multiple neural receptors, then placing receptive fields evenly along a logarithmic scale naturally leads to the psychological Weber-Fechner law. In the visual system, the spacing and width of extrafoveal receptive fields are consistent with logarithmic scaling. Other sets of neural "receptors" appear to show the same qualitative properties, suggesting that this form of neural scaling reflects a solution to a very general problem. This paper argues that these neural scaling laws enable the brain to represent information about the world efficiently without making any assumptions about the statistics of the world. This analysis suggests that the organization of neural scales to represent one-dimensional quantities, including more abstract quantities such as numerosity, time, and allocentric space, should have a uni...

  7. Neural networks with discontinuous/impact activations

    CERN Document Server

    Akhmet, Marat

    2014-01-01

    This book presents as its main subject new models in mathematical neuroscience. A wide range of neural networks models with discontinuities are discussed, including impulsive differential equations, differential equations with piecewise constant arguments, and models of mixed type. These models involve discontinuities, which are natural because huge velocities and short distances are usually observed in devices modeling the networks. A discussion of the models, appropriate for the proposed applications, is also provided. This book also: Explores questions related to the biological underpinning for models of neural networks\\ Considers neural networks modeling using differential equations with impulsive and piecewise constant argument discontinuities Provides all necessary mathematical basics for application to the theory of neural networks Neural Networks with Discontinuous/Impact Activations is an ideal book for researchers and professionals in the field of engineering mathematics that have an interest in app...

  8. Parental involvement

    OpenAIRE

    Ezra S Simon

    2005-01-01

    This study was conducted in Ghana to investigate, (1) factors that predict parental involvement, (2) the relationship between parental home and school involvement and the educational achievement of adolescents, (3) the relationship between parental authoritativeness and the educational achievement of adolescent students, (4) parental involvement serving as a mediator between their authoritativeness and the educational achievement of the students, and (5) whether parental involvement decreases...

  9. Divergent influences of anterior cingulate cortex GABA concentrations on the emotion circuitry

    NARCIS (Netherlands)

    Levar, Nina; van Leeuwen, Judith M C; Denys, Damiaan; Van Wingen, G.

    2017-01-01

    Neuroimaging research has revealed that emotion processing recruits a widespread neural network including the dorsal anterior cingulate cortex (dACC), hippocampus, and amygdala. Recent studies have started to investigate the role of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA)

  10. A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

    Science.gov (United States)

    2011-09-01

    Eisner-Janowicz et al., 2008), as well as the cortex of the uninjured hemisphere (Re- inecke et al., 2003; Rema and Ebner , 2003). Neural reorgani...in rats. Eur. J. Neurosci. 17, 623–627. Rema, V., and Ebner , F.F. (2003). Lesions of mature barrel field cortex interfere with sensory processing and

  11. Optics in neural computation

    Science.gov (United States)

    Levene, Michael John

    In all attempts to emulate the considerable powers of the brain, one is struck by both its immense size, parallelism, and complexity. While the fields of neural networks, artificial intelligence, and neuromorphic engineering have all attempted oversimplifications on the considerable complexity, all three can benefit from the inherent scalability and parallelism of optics. This thesis looks at specific aspects of three modes in which optics, and particularly volume holography, can play a part in neural computation. First, holography serves as the basis of highly-parallel correlators, which are the foundation of optical neural networks. The huge input capability of optical neural networks make them most useful for image processing and image recognition and tracking. These tasks benefit from the shift invariance of optical correlators. In this thesis, I analyze the capacity of correlators, and then present several techniques for controlling the amount of shift invariance. Of particular interest is the Fresnel correlator, in which the hologram is displaced from the Fourier plane. In this case, the amount of shift invariance is limited not just by the thickness of the hologram, but by the distance of the hologram from the Fourier plane. Second, volume holography can provide the huge storage capacity and high speed, parallel read-out necessary to support large artificial intelligence systems. However, previous methods for storing data in volume holograms have relied on awkward beam-steering or on as-yet non- existent cheap, wide-bandwidth, tunable laser sources. This thesis presents a new technique, shift multiplexing, which is capable of very high densities, but which has the advantage of a very simple implementation. In shift multiplexing, the reference wave consists of a focused spot a few millimeters in front of the hologram. Multiplexing is achieved by simply translating the hologram a few tens of microns or less. This thesis describes the theory for how shift

  12. Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

    Science.gov (United States)

    Moretti, Rita; Signori, Riccardo

    2016-01-01

    Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC) and basal ganglia; “emotional affective” apathy may be related to the orbitomedial PFC and ventral striatum; “cognitive apathy” may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of “autoactivation” may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to gray matter atrophy in the anterior cingulate (ACC) and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies, and a reduced speedness in action decision, major responsible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control. We will discuss the importance of these circuits in different pathologies

  13. Neural substrate expansion for the restoration of brain function

    Directory of Open Access Journals (Sweden)

    Han-Chiao Isaac Chen

    2016-01-01

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

  14. Internal models and neural computation in the vestibular system.

    Science.gov (United States)

    Green, Andrea M; Angelaki, Dora E

    2010-01-01

    The vestibular system is vital for motor control and spatial self-motion perception. Afferents from the otolith organs and the semicircular canals converge with optokinetic, somatosensory and motor-related signals in the vestibular nuclei, which are reciprocally interconnected with the vestibulocerebellar cortex and deep cerebellar nuclei. Here, we review the properties of the many cell types in the vestibular nuclei, as well as some fundamental computations implemented within this brainstem-cerebellar circuitry. These include the sensorimotor transformations for reflex generation, the neural computations for inertial motion estimation, the distinction between active and passive head movements, as well as the integration of vestibular and proprioceptive information for body motion estimation. A common theme in the solution to such computational problems is the concept of internal models and their neural implementation. Recent studies have shed new insights into important organizational principles that closely resemble those proposed for other sensorimotor systems, where their neural basis has often been more difficult to identify. As such, the vestibular system provides an excellent model to explore common neural processing strategies relevant both for reflexive and for goal-directed, voluntary movement as well as perception.

  15. Differentiating neural reward responsiveness in autism versus ADHD

    Directory of Open Access Journals (Sweden)

    Gregor Kohls

    2014-10-01

    Full Text Available Although attention deficit hyperactivity disorders (ADHD and autism spectrum disorders (ASD share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC. A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ASD. Shared dysfunction was characterized by fronto-striato-parietal hypoactivation in both clinical groups when money was at stake. Interestingly, lower neural activation within parietal circuitry was associated with higher autistic traits across the entire study sample. In sum, the present findings concur with the assumption that both ASD and ADHD display distinct and shared neural dysfunction in response to reward.

  16. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease.

    Science.gov (United States)

    Petzinger, Giselle M; Fisher, Beth E; McEwen, Sarah; Beeler, Jeff A; Walsh, John P; Jakowec, Michael W

    2013-07-01

    Exercise interventions in individuals with Parkinson's disease incorporate goal-based motor skill training to engage cognitive circuitry important in motor learning. With this exercise approach, physical therapy helps with learning through instruction and feedback (reinforcement) and encouragement to perform beyond self-perceived capability. Individuals with Parkinson's disease become more cognitively engaged with the practice and learning of movements and skills that were previously automatic and unconscious. Aerobic exercise, regarded as important for improvement of blood flow and facilitation of neuroplasticity in elderly people, might also have a role in improvement of behavioural function in individuals with Parkinson's disease. Exercises that incorporate goal-based training and aerobic activity have the potential to improve both cognitive and automatic components of motor control in individuals with mild to moderate disease through experience-dependent neuroplasticity. Basic research in animal models of Parkinson's disease is beginning to show exercise-induced neuroplastic effects at the level of synaptic connections and circuits. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements.

    Science.gov (United States)

    Schoenfelder, Stefan; Furlan-Magaril, Mayra; Mifsud, Borbala; Tavares-Cadete, Filipe; Sugar, Robert; Javierre, Biola-Maria; Nagano, Takashi; Katsman, Yulia; Sakthidevi, Moorthy; Wingett, Steven W; Dimitrova, Emilia; Dimond, Andrew; Edelman, Lucas B; Elderkin, Sarah; Tabbada, Kristina; Darbo, Elodie; Andrews, Simon; Herman, Bram; Higgs, Andy; LeProust, Emily; Osborne, Cameron S; Mitchell, Jennifer A; Luscombe, Nicholas M; Fraser, Peter

    2015-04-01

    The mammalian genome harbors up to one million regulatory elements often located at great distances from their target genes. Long-range elements control genes through physical contact with promoters and can be recognized by the presence of specific histone modifications and transcription factor binding. Linking regulatory elements to specific promoters genome-wide is currently impeded by the limited resolution of high-throughput chromatin interaction assays. Here we apply a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse promoters to identify statistically significant, long-range interactions at restriction fragment resolution, assigning long-range interacting elements to their target genes genome-wide in embryonic stem cells and fetal liver cells. The distal sites contacting active genes are enriched in active histone modifications and transcription factor occupancy, whereas inactive genes contact distal sites with repressive histone marks, demonstrating the regulatory potential of the distal elements identified. Furthermore, we find that coregulated genes cluster nonrandomly in spatial interaction networks correlated with their biological function and expression level. Interestingly, we find the strongest gene clustering in ES cells between transcription factor genes that control key developmental processes in embryogenesis. The results provide the first genome-wide catalog linking gene promoters to their long-range interacting elements and highlight the complex spatial regulatory circuitry controlling mammalian gene expression. © 2015 Schoenfelder et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Ultrafast all-optical modulation with hyperbolic metamaterial integrated in Si photonic circuitry.

    Science.gov (United States)

    Neira, Andres D; Wurtz, Gregory A; Ginzburg, Pavel; Zayats, Anatoly V

    2014-05-05

    The integration of optical metamaterials within silicon integrated photonic circuitry bears significantly potential in the design of low-power, nanoscale footprint, all-optical functionalities. We propose a novel concept and provide detailed analysis of an on-chip ultrafast all-optical modulator based on an hyperbolic metamaterial integrated in a silicon waveguide. The anisotropic metamaterial based on gold nanorods is placed on top of the silicon waveguide to form a modulator with a 300x440x600 nm(3) footprint. For the operating wavelength of 1.5 μm, the optimized geometry of the device has insertion loss of about 5 dB and a modulation depth of 35% with a sub-ps switching rate. The switching energy estimated from nonlinear transient dynamic numerical simulations is 3.7 pJ/bit when the transmission is controlled optically at a wavelength of 532 nm, resonant with the transverse plasmonic mode of the metamaterial. The switching mechanism is based on the control of the hybridization of eigenmodes in the metamaterial slab and the Si waveguide.

  19. Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: Circuitry and mechanical design

    Science.gov (United States)

    Kia, Kaveh Kazemi; Bonabi, Fahimeh

    2012-12-01

    A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 μs. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

  20. Assessing Ink Transfer Performance of Gravure-Offset Fine-Line Circuitry Printing

    Science.gov (United States)

    Cheng, Hsien-Chie; Chen, You-Wei; Chen, Wen-Hwa; Lu, Su-Tsai; Lin, Shih-Ming

    2017-12-01

    In this study, the printing mechanism and performance of gravure-offset fine-line circuitry printing technology are investigated in terms of key printing parameters through experimental and theoretical analyses. First, the contact angles of the ink deposited on different substrates, blankets, and gravure metal plates are experimentally determined; moreover, their temperature and solvent content dependences are analyzed. Next, the ink solvent absorption and evaporation behaviors of the blankets at different temperatures, times, and numbers of printing repetitions are characterized by conducting experiments. In addition, while printing repeatedly, the surface characteristics of the blankets, such as the contact angle, vary with the amount of absorbed ink solvent, further affecting the ink transfer performance (ratio) and printing quality. Accordingly, the surface effect of the blanket due to ink solvent absorption on the ink contact angle is analyzed. Furthermore, the amount of ink transferred from the gravure plate to the blanket in the "off process" and from the blanket to the substrate in the "set process" is evaluated by conducting a simplified plate-to-plate experiment. The influences of loading rate (printing velocity), temperature, and solvent content on the ink transfer performance are addressed. Finally, the ink transfer mechanism is theoretically analyzed for different solvent contents using Surface Evolver. The calculation results are compared with those of the experiment.

  1. A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination

    Science.gov (United States)

    Frittoli, Emanuela; Palamidessi, Andrea; Marighetti, Paola; Confalonieri, Stefano; Bianchi, Fabrizio; Malinverno, Chiara; Mazzarol, Giovanni; Viale, Giuseppe; Martin-Padura, Ines; Garré, Massimilliano; Parazzoli, Dario; Mattei, Valentina; Cortellino, Salvatore; Bertalot, Giovanni

    2014-01-01

    The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5–dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and β3 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program. PMID:25049275

  2. The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior.

    Science.gov (United States)

    McFarland, K; Kalivas, P W

    2001-11-01

    The role of limbic-striato-pallidal circuitry in cocaine-induced reinstatement was evaluated. The transient inhibition of brain nuclei associated with motor systems [including the ventral tegmental area (VTA), dorsal prefrontal cortex (dPFC), core of the nucleus accumbens (NAcore), and ventral pallidum (VP)] prevented cocaine-induced reinstatement. However, only the VP proved to be necessary for food reinstatement, suggesting that the identified circuit is specific to drug-related reinstatement. Supporting the possibility that the VTA-dPFC-NAcore-VP is a series circuit mediating reinstatement, simultaneous unilateral microinjection of GABA agonists into the dPFC in one hemisphere and into the VP in the contralateral hemisphere abolished cocaine reinstatement. Although dopamine projections from the VTA innervate all three forebrain nuclei, the blockade of dopamine receptors only in the dPFC antagonized cocaine-induced reinstatement. Furthermore, DA administration into the dPFC was sufficient to elicit a reinstatement in drug-related responding. These data demonstrate that dopamine release in the dPFC initiates a dPFC-NAcore-VP series circuit that mediates cocaine-induced drug-seeking behavior.

  3. Integrated plasmonic circuitry on a vertical-cavity surface-emitting semiconductor laser platform.

    Science.gov (United States)

    McPolin, Cillian P T; Bouillard, Jean-Sebastien; Vilain, Sebastien; Krasavin, Alexey V; Dickson, Wayne; O'Connor, Daniel; Wurtz, Gregory A; Justice, John; Corbett, Brian; Zayats, Anatoly V

    2016-08-05

    Integrated plasmonic sources and detectors are imperative in the practical development of plasmonic circuitry for bio- and chemical sensing, nanoscale optical information processing, as well as transducers for high-density optical data storage. Here we show that vertical-cavity surface-emitting lasers (VCSELs) can be employed as an on-chip, electrically pumped source or detector of plasmonic signals, when operated in forward or reverse bias, respectively. To this end, we experimentally demonstrate surface plasmon polariton excitation, waveguiding, frequency conversion and detection on a VCSEL-based plasmonic platform. The coupling efficiency of the VCSEL emission to waveguided surface plasmon polariton modes has been optimized using asymmetric plasmonic nanostructures. The plasmonic VCSEL platform validated here is a viable solution for practical realizations of plasmonic functionalities for various applications, such as those requiring sub-wavelength field confinement, refractive index sensitivity or optical near-field transduction with electrically driven sources, thus enabling the realization of on-chip optical communication and lab-on-a-chip devices.

  4. Taste Reward Circuitry Related Brain Structures Characterize Ill and Recovered Anorexia Nervosa and Bulimia Nervosa

    Science.gov (United States)

    Frank, Guido K.; Shott, Megan E.; Hagman, Jennifer O.; Mittal, Vijay A.

    2013-01-01

    Objective The pathophysiology of the eating disorder anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. Here we assessed taste pleasantness and reward sensitivity in relation to brain structure, which might be related to food avoidance commonly seen in eating disorders. Method We used structural magnetic resonance brain imaging to study gray and white matter volumes in individuals with restricting type currently ill (n = 19) or recovered-anorexia nervosa (n = 24), bulimia nervosa (n= 19) and healthy control women (n=24). Results All eating disorder groups showed increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manually tracing confirmed larger gyrus rectus volume, and predicted taste pleasantness across all groups. The analyses also indicated other morphological differences between diagnostic categories: Ill and recovered-anorexia nervosa had increased right, while bulimia nervosa had increased left antero-ventral insula gray matter volumes compared to controls. Furthermore, dorsal striatum volumes were reduced in recovered-anorexia and bulimia nervosa, and predicted sensitivity to reward in the eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas when compared to healthy controls. Notably, the results held when controlling for a range of covariates (e.g., age, depression, anxiety, medications). Conclusion Brain structure in medial orbitofrontal cortex, insula and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

  5. Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System.

    Directory of Open Access Journals (Sweden)

    Mathias Foo

    2016-02-01

    Full Text Available A wide range of organisms features molecular machines, circadian clocks, which generate endogenous oscillations with ~24 h periodicity and thereby synchronize biological processes to diurnal environmental fluctuations. Recently, it has become clear that plants harbor more complex gene regulatory circuits within the core circadian clocks than other organisms, inspiring a fundamental question: are all these regulatory interactions between clock genes equally crucial for the establishment and maintenance of circadian rhythms? Our mechanistic simulation for Arabidopsis thaliana demonstrates that at least half of the total regulatory interactions must be present to express the circadian molecular profiles observed in wild-type plants. A set of those essential interactions is called herein a kernel of the circadian system. The kernel structure unbiasedly reveals four interlocked negative feedback loops contributing to circadian rhythms, and three feedback loops among them drive the autonomous oscillation itself. Strikingly, the kernel structure, as well as the whole clock circuitry, is overwhelmingly composed of inhibitory, rather than activating, interactions between genes. We found that this tendency underlies plant circadian molecular profiles which often exhibit sharply-shaped, cuspidate waveforms. Through the generation of these cuspidate profiles, inhibitory interactions may facilitate the global coordination of temporally-distant clock events that are markedly peaked at very specific times of day. Our systematic approach resulting in experimentally-testable predictions provides insights into a design principle of biological clockwork, with implications for synthetic biology.

  6. Neural Reranking for Named Entity Recognition

    OpenAIRE

    Yang, Jie; Zhang, Yue; Dong, Fei

    2017-01-01

    We propose a neural reranking system for named entity recognition (NER). The basic idea is to leverage recurrent neural network models to learn sentence-level patterns that involve named entity mentions. In particular, given an output sentence produced by a baseline NER model, we replace all entity mentions, such as \\textit{Barack Obama}, into their entity types, such as \\textit{PER}. The resulting sentence patterns contain direct output information, yet is less sparse without specific named ...

  7. Neural Darwinism and consciousness.

    Science.gov (United States)

    Seth, Anil K; Baars, Bernard J

    2005-03-01

    Neural Darwinism (ND) is a large scale selectionist theory of brain development and function that has been hypothesized to relate to consciousness. According to ND, consciousness is entailed by reentrant interactions among neuronal populations in the thalamocortical system (the 'dynamic core'). These interactions, which permit high-order discriminations among possible core states, confer selective advantages on organisms possessing them by linking current perceptual events to a past history of value-dependent learning. Here, we assess the consistency of ND with 16 widely recognized properties of consciousness, both physiological (for example, consciousness is associated with widespread, relatively fast, low amplitude interactions in the thalamocortical system), and phenomenal (for example, consciousness involves the existence of a private flow of events available only to the experiencing subject). While no theory accounts fully for all of these properties at present, we find that ND and its recent extensions fare well.

  8. Introduction to neural networks

    CERN Document Server

    James, Frederick E

    1994-02-02

    1. Introduction and overview of Artificial Neural Networks. 2,3. The Feed-forward Network as an inverse Problem, and results on the computational complexity of network training. 4.Physics applications of neural networks.

  9. Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation.

    Science.gov (United States)

    Balashova, Olga A; Visina, Olesya; Borodinsky, Laura N

    2017-04-15

    Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor 1 (Folr1; also known as FRα) impairs neural tube formation and leads to NTDs. Folr1 knockdown in neural plate cells only is necessary and sufficient to induce NTDs. Folr1-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model in which the folate receptor interacts with cell adhesion molecules, thus regulating the apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism could unveil novel cellular and molecular events mediated by folate and lead to new ways of preventing NTDs. © 2017. Published by The Company of Biologists Ltd.

  10. Neural song preference during vocal learning in the zebra finch depends on age and state.

    Science.gov (United States)

    Nick, Teresa A; Konishi, Masakazu

    2005-02-05

    The zebra finch acquires its song by first memorizing a model song from a tutor and then matching its own vocalizations to the memory trace of the tutor song, called a template. Neural mechanisms underlying this process require a link between the neural memory trace and the premotor song circuitry, which drives singing. We now report that a premotor song nucleus responds more to the tutor song model than to every other stimulus examined, including the bird's own song (BOS). Neural tuning to the song model occurred only during waking and peaked during the template-matching period of development, when the vocal motor output is sculpted to match the tutor song. During the same developmental phase, the BOS was the most effective excitatory stimulus during sleep. The preference for BOS compared to tutor song inverted with sleep/wake state. Thus, song preference shifts with development and state. 2004 Wiley Periodicals, Inc.

  11. A case for spiking neural network simulation based on configurable multiple-FPGA systems.

    Science.gov (United States)

    Yang, Shufan; Wu, Qiang; Li, Renfa

    2011-09-01

    Recent neuropsychological research has begun to reveal that neurons encode information in the timing of spikes. Spiking neural network simulations are a flexible and powerful method for investigating the behaviour of neuronal systems. Simulation of the spiking neural networks in software is unable to rapidly generate output spikes in large-scale of neural network. An alternative approach, hardware implementation of such system, provides the possibility to generate independent spikes precisely and simultaneously output spike waves in real time, under the premise that spiking neural network can take full advantage of hardware inherent parallelism. We introduce a configurable FPGA-oriented hardware platform for spiking neural network simulation in this work. We aim to use this platform to combine the speed of dedicated hardware with the programmability of software so that it might allow neuroscientists to put together sophisticated computation experiments of their own model. A feed-forward hierarchy network is developed as a case study to describe the operation of biological neural systems (such as orientation selectivity of visual cortex) and computational models of such systems. This model demonstrates how a feed-forward neural network constructs the circuitry required for orientation selectivity and provides platform for reaching a deeper understanding of the primate visual system. In the future, larger scale models based on this framework can be used to replicate the actual architecture in visual cortex, leading to more detailed predictions and insights into visual perception phenomenon.

  12. First realization of a tracking detector for high energy physics experiments based on Josephson digital readout circuitry

    CERN Document Server

    Pagano, S; Esposito, A P; Mukhanov, O; Rylov, S

    1999-01-01

    We have designed and realized a prototype of a high energy particle microstrip detector with Josephson readout circuits. The key features of this device are: minimum ionizing particle sensitivity, due to the use of semiconductive sensors, fast speed and radiation hardness, due to the use of superconductive circuitry, and current discrimination, which allows the use of several types of semiconductors as detector (Si, GaAs, CVD-diamond) without loss in performances. The Josephson circuitry, made by a combination of RSFQ and latching logic gates, realizes an 8-bit current discriminator and parallel to serial converter and can be directly interfaced to room temperature electronics. This device, which is designed for application as vertex detector for the Compass and LHC-B accelerator experiments, has been tested with small radioactive sources acid will undergo to a test beam at the CERN SPS facility with 24 GeV/c protons. Current results and future perspectives will be reported. (11 refs).

  13. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology

    Science.gov (United States)

    Aravanis, Alexander M.; Wang, Li-Ping; Zhang, Feng; Meltzer, Leslie A.; Mogri, Murtaza Z.; Schneider, M. Bret; Deisseroth, Karl

    2007-09-01

    Neural interface technology has made enormous strides in recent years but stimulating electrodes remain incapable of reliably targeting specific cell types (e.g. excitatory or inhibitory neurons) within neural tissue. This obstacle has major scientific and clinical implications. For example, there is intense debate among physicians, neuroengineers and neuroscientists regarding the relevant cell types recruited during deep brain stimulation (DBS); moreover, many debilitating side effects of DBS likely result from lack of cell-type specificity. We describe here a novel optical neural interface technology that will allow neuroengineers to optically address specific cell types in vivo with millisecond temporal precision. Channelrhodopsin-2 (ChR2), an algal light-activated ion channel we developed for use in mammals, can give rise to safe, light-driven stimulation of CNS neurons on a timescale of milliseconds. Because ChR2 is genetically targetable, specific populations of neurons even sparsely embedded within intact circuitry can be stimulated with high temporal precision. Here we report the first in vivo behavioral demonstration of a functional optical neural interface (ONI) in intact animals, involving integrated fiberoptic and optogenetic technology. We developed a solid-state laser diode system that can be pulsed with millisecond precision, outputs 20 mW of power at 473 nm, and is coupled to a lightweight, flexible multimode optical fiber, ~200 µm in diameter. To capitalize on the unique advantages of this system, we specifically targeted ChR2 to excitatory cells in vivo with the CaMKIIα promoter. Under these conditions, the intensity of light exiting the fiber (~380 mW mm-2) was sufficient to drive excitatory neurons in vivo and control motor cortex function with behavioral output in intact rodents. No exogenous chemical cofactor was needed at any point, a crucial finding for in vivo work in large mammals. Achieving modulation of behavior with optical control of

  14. Apollo experience report: Detection and minimization of ignition hazards from water/glycol contamination of silver-clad electrical circuitry

    Science.gov (United States)

    Downs, W. R.

    1976-01-01

    The potential flammability hazard when a water/glycol solution contacts defectively insulated silver-clad copper circuitry or electrical components carrying a direct current is described. The chemical reactions and means for detecting them are explained. Methods for detecting and cleaning contaminated areas and the use of inhibitors to arrest chemical reactivity are also explained. Preventive measures to minimize hazards are given. Photomicrographs of the chemical reactions occurring on silver clad wires are also included.

  15. Analysis of graph invariants in functional neocortical circuitry reveals generalized features common to three areas of sensory cortex.

    Directory of Open Access Journals (Sweden)

    Suchin S Gururangan

    2014-07-01

    Full Text Available Correlations in local neocortical spiking activity can provide insight into the underlying organization of cortical microcircuitry. However, identifying structure in patterned multi-neuronal spiking remains a daunting task due to the high dimensionality of the activity. Using two-photon imaging, we monitored spontaneous circuit dynamics in large, densely sampled neuronal populations within slices of mouse primary auditory, somatosensory, and visual cortex. Using the lagged correlation of spiking activity between neurons, we generated functional wiring diagrams to gain insight into the underlying neocortical circuitry. By establishing the presence of graph invariants, which are label-independent characteristics common to all circuit topologies, our study revealed organizational features that generalized across functionally distinct cortical regions. Regardless of sensory area, random and k-nearest neighbors null graphs failed to capture the structure of experimentally derived functional circuitry. These null models indicated that despite a bias in the data towards spatially proximal functional connections, functional circuit structure is best described by non-random and occasionally distal connections. Eigenvector centrality, which quantifies the importance of a neuron in the temporal flow of circuit activity, was highly related to feedforwardness in all functional circuits. The number of nodes participating in a functional circuit did not scale with the number of neurons imaged regardless of sensory area, indicating that circuit size is not tied to the sampling of neocortex. Local circuit flow comprehensively covered angular space regardless of the spatial scale that we tested, demonstrating that circuitry itself does not bias activity flow toward pia. Finally, analysis revealed that a minimal numerical sample size of neurons was necessary to capture at least 90 percent of functional circuit topology. These data and analyses indicated that

  16. Nanomaterial-enabled neural stimulation

    Directory of Open Access Journals (Sweden)

    Yongchen eWang

    2016-03-01

    Full Text Available Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed.

  17. High-Density Liquid-State Machine Circuitry for Time-Series Forecasting.

    Science.gov (United States)

    Rosselló, Josep L; Alomar, Miquel L; Morro, Antoni; Oliver, Antoni; Canals, Vincent

    2016-08-01

    Spiking neural networks (SNN) are the last neural network generation that try to mimic the real behavior of biological neurons. Although most research in this area is done through software applications, it is in hardware implementations in which the intrinsic parallelism of these computing systems are more efficiently exploited. Liquid state machines (LSM) have arisen as a strategic technique to implement recurrent designs of SNN with a simple learning methodology. In this work, we show a new low-cost methodology to implement high-density LSM by using Boolean gates. The proposed method is based on the use of probabilistic computing concepts to reduce hardware requirements, thus considerably increasing the neuron count per chip. The result is a highly functional system that is applied to high-speed time series forecasting.

  18. Perceptual alternation in obsessive compulsive disorder--implications for a role of the cortico-striatal circuitry in mediating awareness.

    Science.gov (United States)

    Li, C S; Chen, M C; Yang, Y Y; Chang, H L; Liu, C Y; Shen, S; Chen, C Y

    2000-06-15

    Mounting evidence suggests that obsessive compulsive disorder (OCD) results from functional aberrations of the fronto-striatal circuitry. However, empirical studies of the behavioral manifestations of OCD have been relatively lacking. The present study employs a behavioral task that allows a quantitative measure of how alternative percepts are formed from one moment to another, a process mimicking the brain state in which different thoughts and imageries compete for access to awareness. Eighteen patients with OCD, 12 with generalized anxiety disorder, and 18 normal subjects participated in the experiment, in which they viewed one of the three Schröder staircases and responded by pressing a key to each perceptual reversal. The results demonstrate that the patients with OCD have a higher perceptual alternation rate than the normal controls. Moreover, the frequency of perceptual alternation is significantly correlated with the Yale-Brown obsessive compulsive and the Hamilton anxiety scores. The increase in the frequency of perceptual reversals cannot easily be accounted for by learning or by different patterns of eye fixations on the task. These results provide further evidence that an impairment of the inhibitory function of the cortico-striatal circuitry might underlie the etiology of OCD. The implications of the results for a general role of the cortico-striatal circuitry in mediating awareness are discussed.

  19. Effects of intranasal oxytocin on neural processing within a socially relevant neural circuit.

    Science.gov (United States)

    Singh, Fiza; Nunag, Jason; Muldoon, Glennis; Cadenhead, Kristin S; Pineda, Jaime A; Feifel, David

    2016-03-01

    Dysregulation of the Mirror Neuron System (MNS) in schizophrenia (SCZ) may underlie the cognitive and behavioral manifestations of social dysfunction associated with that disorder. In healthy subjects intranasal (IN) oxytocin (OT) improves neural processing in the MNS and is associated with improved social cognition. OT's brain effects can be measured through its modulation of the MNS by suppressing EEG mu-band electrical activity (8-13Hz) in response to motion perception. Although IN OT's effects on social cognition have been tested in SCZ, OT's impact on the MNS has not been evaluated to date. Therefore, we designed a study to investigate the effects of two different OT doses on biological motion-induced mu suppression in SCZ and healthy subjects. EEG recordings were taken after each subject received a single IN administration of placebo, OT-24IU and OT-48IU in randomized order in a double-blind crossover design. The results provide support for OT's regulation of the MNS in both healthy and SCZ subjects, with the optimal dose dependent on diagnostic group and sex of subject. A statistically significant response was seen in SCZ males only, indicating a heightened sensitivity to those effects, although sex hormone related effects cannot be ruled out. In general, OT appears to have positive effects on neural circuitry that supports social cognition and socially adaptive behaviors. Published by Elsevier B.V.

  20. An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson’s Disease

    Science.gov (United States)

    ZGALJARDIC, DENNIS J.; BOROD, JOAN C.; FOLDI, NANCY S.; MATTIS, PAUL J.; GORDON, MARK F.; FEIGIN, ANDREW; EIDELBERG, DAVID

    2015-01-01

    Parkinson’s disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson’s disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function. PMID:16840240

  1. Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain stimulation for OCD.

    Science.gov (United States)

    Greenberg, Benjamin D; Rauch, Scott L; Haber, Suzanne N

    2010-01-01

    patterns of potential benefits and burdens. Translational research to elucidate how targeting specific nodes in putative OCD circuitry might lead to therapeutic gains is accelerating in tandem with clinical use.

  2. Hyperleptinemia in Neonatally Overfed Female Rats Does Not Dysregulate Feeding Circuitry

    Directory of Open Access Journals (Sweden)

    Ilvana Ziko

    2017-10-01

    Full Text Available Neonatal overfeeding during the first weeks of life in male rats is associated with a disruption in the peripheral and central leptin systems. Neonatally overfed male rats have increased circulating leptin in the first 2 weeks of life, which corresponds to an increase in body weight compared to normally fed counterparts. These effects are associated with a short-term disruption in the connectivity of neuropeptide Y (NPY, agouti-related peptide (AgRP, and pro-opiomelanocortin (POMC neurons within the regions of the hypothalamus responsible for control of energy balance and food intake. Female rats that are overfed during the first weeks of their life experience similar changes in circulating leptin levels as well as in their body weight. However, it has not yet been studied whether these metabolic changes are associated with the same central effects as observed in males. Here, we hypothesized that hyperleptinemia associated with neonatal overfeeding would lead to changes in central feeding circuitry in females as it does in males. We assessed hypothalamic NPY, AgRP, and POMC gene expression and immunoreactivity at 7, 12, or 14 days of age, as well as neuronal activation in response to exogenous leptin in neonatally overfed and control female rats. Neonatally overfed female rats were hyperleptinemic and were heavier than controls. However, these metabolic changes were not mirrored centrally by changes in hypothalamic NPY, AGRP, and POMC fiber density. These findings are suggestive of sex differences in the effects of neonatal overfeeding and of differences in the ability of the female and male central systems to respond to changes in the early life nutritional environment.

  3. Feedforward Backpropagation Neural Networks in Prediction of Farmer Risk Preferences

    OpenAIRE

    Kastens, Terry L.; Featherstone, Allen M.

    1996-01-01

    An out-of-sample prediction of Kansas farmers' responses to five surveyed questions involving risk is used to compare ordered multinomial logistic regression models with feedforward backpropagation neural network models. Although the logistic models often predict more accurately than the neural network models in a mean-squared error sense, the neural network models are shown to be more accommodating of loss functions associated with a desire to predict certain combinations of categorical resp...

  4. Ontogeny of avian thermoregulation from a neural point of view

    OpenAIRE

    Baarendse, P.J.J.; Debonne, M.; Decuypere, M.P.; Kemp, B.; Brand, van den, H.

    2007-01-01

    The ontogeny of thermoregulation differs among (avian) species, but in all species both neural and endocrinological processes are involved. In this review the neural processes in ontogeny of thermoregulation during the prenatal and early postnatal phase are discussed. Only in a few avian species (chicken, ducklings) the ontogeny of some important neural structures are described. In the early post hatching phase, peripheral and deep-body thermoreceptors are present and functional, even in altr...

  5. Differential neural contributions to native- and foreign-language talker identification.

    Science.gov (United States)

    Perrachione, Tyler K; Pierrehumbert, Janet B; Wong, Patrick C M

    2009-12-01

    Humans are remarkably adept at identifying individuals by the sound of their voice, a behavior supported by the nervous system's ability to integrate information from voice and speech perception. Talker-identification abilities are significantly impaired when listeners are unfamiliar with the language being spoken. Recent behavioral studies describing the language-familiarity effect implicate functionally integrated neural systems for speech and voice perception, yet specific neuroscientific evidence demonstrating the basis for such integration has not yet been shown. Listeners in the present study learned to identify voices speaking a familiar (native) or unfamiliar (foreign) language. The talker-identification performance of neural circuitry in each cerebral hemisphere was assessed using dichotic listening. To determine the relative contribution of circuitry in each hemisphere to ecological (binaural) talker identification abilities, we compared the predictive capacity of dichotic performance on binaural performance across languages. Listeners' right-ear (left hemisphere) performance was a better predictor of binaural accuracy in their native language than a foreign one. This enhanced role of the classically language-dominant left hemisphere in listeners' native language demonstrates functionally integrated neural systems for speech and voice perception during talker identification.

  6. Whole-brain 3D mapping of human neural transplant innervation.

    Science.gov (United States)

    Doerr, Jonas; Schwarz, Martin Karl; Wiedermann, Dirk; Leinhaas, Anke; Jakobs, Alina; Schloen, Florian; Schwarz, Inna; Diedenhofen, Michael; Braun, Nils Christian; Koch, Philipp; Peterson, Daniel A; Kubitscheck, Ulrich; Hoehn, Mathias; Brüstle, Oliver

    2017-01-19

    While transplantation represents a key tool for assessing in vivo functionality of neural stem cells and their suitability for neural repair, little is known about the integration of grafted neurons into the host brain circuitry. Rabies virus-based retrograde tracing has developed into a powerful approach for visualizing synaptically connected neurons. Here, we combine this technique with light sheet fluorescence microscopy (LSFM) to visualize transplanted cells and connected host neurons in whole-mouse brain preparations. Combined with co-registration of high-precision three-dimensional magnetic resonance imaging (3D MRI) reference data sets, this approach enables precise anatomical allocation of the host input neurons. Our data show that the same neural donor cell population grafted into different brain regions receives highly orthotopic input. These findings indicate that transplant connectivity is largely dictated by the circuitry of the target region and depict rabies-based transsynaptic tracing and LSFM as efficient tools for comprehensive assessment of host-donor cell innervation.

  7. Evolving a neural olfactorimotor system in virtual and real olfactory environments.

    Science.gov (United States)

    Rhodes, Paul A; Anderson, Todd O

    2012-01-01

    To provide a platform to enable the study of simulated olfactory circuitry in context, we have integrated a simulated neural olfactorimotor system with a virtual world which simulates both computational fluid dynamics as well as a robotic agent capable of exploring the simulated plumes. A number of the elements which we developed for this purpose have not, to our knowledge, been previously assembled into an integrated system, including: control of a simulated agent by a neural olfactorimotor system; continuous interaction between the simulated robot and the virtual plume; the inclusion of multiple distinct odorant plumes and background odor; the systematic use of artificial evolution driven by olfactorimotor performance (e.g., time to locate a plume source) to specify parameter values; the incorporation of the realities of an imperfect physical robot using a hybrid model where a physical robot encounters a simulated plume. We close by describing ongoing work toward engineering a high dimensional, reversible, low power electronic olfactory sensor which will allow olfactorimotor neural circuitry evolved in the virtual world to control an autonomous olfactory robot in the physical world. The platform described here is intended to better test theories of olfactory circuit function, as well as provide robust odor source localization in realistic environments.

  8. Neural correlates of paediatric dysgraphia.

    Science.gov (United States)

    Van Hoorn, Jessika F; Maathuis, Carel G B; Hadders-Algra, Mijna

    2013-11-01

    Writing is an important skill that is related both to school performance and to psychosocial outcomes such as the child's self-esteem. Deficits in handwriting performance are frequently encountered in children with developmental coordination disorder. This review focuses on what is known about the neural correlates of atypical handwriting in children. Knowledge of the neural correlates is derived from studies using clinical case designs (e.g. lesion studies), studies using neuroimaging, and assessment of minor neurological dysfunction. The two functional imaging studies suggest a contribution of cortical areas and the cerebellum. The largest study indicated that cortical areas in all regions of the brain are involved (frontal, temporal, parietal, and occipital). The two lesion studies confirmed cerebellar involvement. The findings of the study on minor neurological dysfunction in children with writing problems correspond to the imaging results. The limited data on the neural substrate of paediatric dysgraphia suggest that at least a subset of the children with dysgraphia have dysfunctions in extensive supraspinal networks. In others, dysfunction may be restricted to either the cerebellum or specific cortical sites. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

  9. Neural Network Spectral Robustness under Perturbations of the Underlying Graph.

    Science.gov (United States)

    Rădulescu, Anca

    2016-01-01

    Recent studies have been using graph-theoretical approaches to model complex networks (such as social, infrastructural, or biological networks) and how their hardwired circuitry relates to their dynamic evolution in time. Understanding how configuration reflects on the coupled behavior in a system of dynamic nodes can be of great importance, for example, in the context of how the brain connectome is affecting brain function. However, the effect of connectivity patterns on network dynamics is far from being fully understood. We study the connections between edge configuration and dynamics in a simple oriented network composed of two interconnected cliques (representative of brain feedback regulatory circuitry). In this article our main goal is to study the spectra of the graph adjacency and Laplacian matrices, with a focus on three aspects in particular: (1) the sensitivity and robustness of the spectrum in response to varying the intra- and intermodular edge density, (2) the effects on the spectrum of perturbing the edge configuration while keeping the densities fixed, and (3) the effects of increasing the network size. We study some tractable aspects analytically, then simulate more general results numerically, thus aiming to motivate and explain our further work on the effect of these patterns on the network temporal dynamics and phase transitions. We discuss the implications of such results to modeling brain connectomics. We suggest potential applications to understanding synaptic restructuring in learning networks and the effects of network configuration on function of regulatory neural circuits.

  10. A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating.

    Science.gov (United States)

    Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

    2013-12-04

    A primary function of males for many species involves mating with females for reproduction. Drosophila melanogaster males respond to the presence of other males by prolonging mating duration to increase the chance of passing on their genes. To understand the basis of such complex behaviors, we examine the genetic network and neural circuits that regulate rival-induced Longer-Mating-Duration (LMD). Here, we identify a small subset of clock neurons in the male brain that regulate LMD via neuropeptide signaling. LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s-LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal activities of a subset of clock neurons involved in neuropeptide signaling for LMD. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Neural bases of accented speech perception

    Directory of Open Access Journals (Sweden)

    Patti eAdank

    2015-10-01

    Full Text Available The recognition of unfamiliar regional and foreign accents represents a challenging task for the speech perception system (Adank, Evans, Stuart-Smith, & Scott, 2009; Floccia, Goslin, Girard, & Konopczynski, 2006. Despite the frequency with which we encounter such accents, the neural mechanisms supporting successful perception of accented speech are poorly understood. Nonetheless, candidate neural substrates involved in processing speech in challenging listening conditions, including accented speech, are beginning to be identified. This review will outline neural bases associated with perception of accented speech in the light of current models of speech perception, and compare these data to brain areas associated with processing other speech distortions. We will subsequently evaluate competing models of speech processing with regards to neural processing of accented speech. See Cristia et al. (2012 for an in-depth overview of behavioural aspects of accent processing.

  12. Screening for Open Neural Tube Defects.

    Science.gov (United States)

    Krantz, David A; Hallahan, Terrence W; Carmichael, Jonathan B

    2016-06-01

    Biochemical prenatal screening was initiated with the use of maternal serum alpha fetoprotein to screen for open neural tube defects. Screening now includes multiple marker and sequential screening protocols involving serum and ultrasound markers to screen for aneuploidy. Recently cell-free DNA screening for aneuploidy has been initiated, but does not screen for neural tube defects. Although ultrasound is highly effective in identifying neural tube defects in high-risk populations, in decentralized health systems maternal serum screening still plays a significant role. Abnormal maternal serum alpha fetoprotein alone or in combination with other markers may indicate adverse pregnancy outcome in the absence of open neural tube defects. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Neural Networks in Mobile Robot Motion

    Directory of Open Access Journals (Sweden)

    Danica Janglová

    2004-03-01

    Full Text Available This paper deals with a path planning and intelligent control of an autonomous robot which should move safely in partially structured environment. This environment may involve any number of obstacles of arbitrary shape and size; some of them are allowed to move. We describe our approach to solving the motion-planning problem in mobile robot control using neural networks-based technique. Our method of the construction of a collision-free path for moving robot among obstacles is based on two neural networks. The first neural network is used to determine the “free” space using ultrasound range finder data. The second neural network “finds” a safe direction for the next robot section of the path in the workspace while avoiding the nearest obstacles. Simulation examples of generated path with proposed techniques will be presented.

  14. Neural Networks in Mobile Robot Motion

    Directory of Open Access Journals (Sweden)

    Danica Janglova

    2008-11-01

    Full Text Available This paper deals with a path planning and intelligent control of an autonomous robot which should move safely in partially structured environment. This environment may involve any number of obstacles of arbitrary shape and size; some of them are allowed to move. We describe our approach to solving the motion-planning problem in mobile robot control using neural networks-based technique. Our method of the construction of a collision-free path for moving robot among obstacles is based on two neural networks. The first neural network is used to determine the "free" space using ultrasound range finder data. The second neural network "finds" a safe direction for the next robot section of the path in the workspace while avoiding the nearest obstacles. Simulation examples of generated path with proposed techniques will be presented.

  15. Neural bases of accented speech perception.

    Science.gov (United States)

    Adank, Patti; Nuttall, Helen E; Banks, Briony; Kennedy-Higgins, Daniel

    2015-01-01

    The recognition of unfamiliar regional and foreign accents represents a challenging task for the speech perception system (Floccia et al., 2006; Adank et al., 2009). Despite the frequency with which we encounter such accents, the neural mechanisms supporting successful perception of accented speech are poorly understood. Nonetheless, candidate neural substrates involved in processing speech in challenging listening conditions, including accented speech, are beginning to be identified. This review will outline neural bases associated with perception of accented speech in the light of current models of speech perception, and compare these data to brain areas associated with processing other speech distortions. We will subsequently evaluate competing models of speech processing with regards to neural processing of accented speech. See Cristia et al. (2012) for an in-depth overview of behavioral aspects of accent processing.

  16. NEURAL CORRELATES FOR APATHY: FRONTAL - PREFRONTAL AND PARIETAL CORTICAL - SUBCORTICAL CIRCUITS

    Directory of Open Access Journals (Sweden)

    Rita Moretti

    2016-12-01

    Full Text Available Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional invovlement; it is an important and heavy-burden clinical condition which strongly impacts in every day life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC and basal ganglia; emotional affective apathy may be related to the orbitomedial PFC and ventral striatum; cognitive apathy may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of autoactivation may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to grey matter atrophy in the anterior cingulate (ACC and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies and a reduced speedness in action decsion, major resposnible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control.We will discuss the importance of these circuits in different pathologies

  17. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  18. Abnormal structure of fear circuitry in pediatric post-traumatic stress disorder.

    Science.gov (United States)

    Keding, Taylor J; Herringa, Ryan J

    2015-02-01

    Structural brain studies of adult post-traumatic stress disorder (PTSD) show reduced gray matter volume (GMV) in fear regulatory areas including the ventromedial prefrontal cortex (vmPFC) and hippocampus. Surprisingly, neither finding has been reported in pediatric PTSD. One possibility is that they represent age-dependent effects that are not fully apparent until adulthood. In addition, lower-resolution MRI and image processing in prior studies may have limited detection of such differences. Here we examine fear circuitry GMV, including age-related differences, using higher-resolution MRI in pediatric PTSD vs healthy youth. In a cross-sectional design, 3 T anatomical brain MRI was acquired in 27 medication-free youth with PTSD and 27 healthy non-traumatized youth of comparable age, sex, and IQ. Voxel-based morphometry was used to compare GMV in a priori regions including the medial prefrontal cortex and amygdala/hippocampus. Compared with healthy youth, PTSD youth had reduced GMV but no age-related differences in anterior vmPFC (BA 10/11, Z=4.5), which inversely correlated with PTSD duration. In contrast, although there was no overall group difference in hippocampal volume, a group × age interaction (Z=3.6) was present in the right anterior hippocampus. Here, age positively predicted hippocampal volume in healthy youth but negatively predicted volume in PTSD youth. Within the PTSD group, re-experiencing symptoms inversely correlated with subgenual anterior cingulate cortex (sgACC, Z=3.7) and right anterior hippocampus (Z=3.5) GMV. Pediatric PTSD is associated with abnormal structure of the vmPFC and age-related differences in the hippocampus, regions important in the extinction and contextual gating of fear. Reduced anterior vmPFC volume may confer impaired recovery from illness, consistent with its role in the allocation of attentional resources. In contrast, individual differences in sgACC volume were associated with re-experiencing symptoms, consistent with

  19. Neural Networks for Language Identification: A Comparative Study.

    Science.gov (United States)

    MacNamara, Shane; Cunningham, Padraig; Byrne, John

    1998-01-01

    Analyzes a neural network for its ability to perform a task involving identification of the language entries in a 19th-century library catalog containing entries in 14 different languages. Compares the neural network's performance with that of trigrams and a suffix/morphology analysis; the trigrams prove to be superior. (AEF)

  20. Ontogeny of avian thermoregulation from a neural point of view

    NARCIS (Netherlands)

    Baarendse, P.J.J.; Debonne, M.; Decuypere, M.P.; Kemp, B.; Brand, van den H.

    2007-01-01

    The ontogeny of thermoregulation differs among (avian) species, but in all species both neural and endocrinological processes are involved. In this review the neural processes in ontogeny of thermoregulation during the prenatal and early postnatal phase are discussed. Only in a few avian species

  1. General anesthesia: a gateway to modulate synapse formation and neural plasticity?

    Science.gov (United States)

    Vutskits, Laszlo

    2012-11-01

    Appropriate balance between excitatory and inhibitory neural activity patterns is of utmost importance in the maintenance of neuronal homeostasis. General anesthetic-induced pharmacological interference with this equilibrium results not only in a temporary loss of consciousness but can also initiate long-term changes in brain function. Although these alterations were initially considered deleterious, recent observations suggest that at least under some specific conditions, they may eventually improve neural function. The goal of this review is to provide insights into the mechanisms underlying these dual effects. Basic science issues on the important role of critical periods during neural circuitry assembly will be discussed to better understand how even brief exposures to general anesthetics could initiate context-dependent lasting changes in neuronal structure and function. Recent series of observations suggesting a developmental stage-dependent impact of these drugs on synaptogenesis will then be summarized together with currently known molecular mechanisms underlying these effects. Particular emphasis will be placed on how anesthetic drugs modulate neural plasticity in the adult brain and how this may improve neural function under some pathological states. The ensemble of these new observations strongly suggests that general anesthetics should not merely be considered toxic drugs but rather acknowledged as robust, context-dependent modulators of neural plasticity.

  2. Single-Trial Neural Correlates of Arm Movement Preparation

    Science.gov (United States)

    Afshar, Afsheen; Santhanam, Gopal; Yu, Byron M.; Ryu, Stephen I.; Sahani, Maneesh; Shenoy, Krishna V.

    2011-01-01

    Summary The process by which neural circuitry in the brain plans and executes arm movements is not well understood. Prevailing data (single-neuron and field potential recordings) do not reveal how individual neurons’ activities are coordinated within the population, and thus inferences about how the neural circuit forms a motor plan have been indirect. Here we frame and test a new ‘initial condition hypothesis’ in which the reaction time (RT) of upcoming movements may be predicted on each trial using neurons’ moment-by-moment firing rates and rates of change of those rates. Using microelectrode array recordings from premotor cortex of monkeys performing delayed-reach movements, we compare such single-trial RT predictions to those of other theories. The initial condition hypothesis model can explain approximately four-fold more RT variance than the best alternative method. Thus, the initial condition hypothesis elucidates a new view of the relationship between single-trial preparatory neural population dynamics and single-trial behavior. PMID:21835350

  3. A Sub-millimeter, Inductively Powered Neural Stimulator

    Directory of Open Access Journals (Sweden)

    Daniel K. Freeman

    2017-11-01

    Full Text Available Wireless neural stimulators are being developed to address problems associated with traditional lead-based implants. However, designing wireless stimulators on the sub-millimeter scale (<1 mm3 is challenging. As device size shrinks, it becomes difficult to deliver sufficient wireless power to operate the device. Here, we present a sub-millimeter, inductively powered neural stimulator consisting only of a coil to receive power, a capacitor to tune the resonant frequency of the receiver, and a diode to rectify the radio-frequency signal to produce neural excitation. By replacing any complex receiver circuitry with a simple rectifier, we have reduced the required voltage levels that are needed to operate the device from 0.5 to 1 V (e.g., for CMOS to ~0.25–0.5 V. This reduced voltage allows the use of smaller receive antennas for power, resulting in a device volume of 0.3–0.5 mm3. The device was encapsulated in epoxy, and successfully passed accelerated lifetime tests in 80°C saline for 2 weeks. We demonstrate a basic proof-of-concept using stimulation with tens of microamps of current delivered to the sciatic nerve in rat to produce a motor response.

  4. Impaired fear extinction in adolescent rodents: Behavioural and neural analyses.

    Science.gov (United States)

    Baker, Kathryn D; Bisby, Madelyne A; Richardson, Rick

    2016-11-01

    Despite adolescence being a developmental window of vulnerability, up until very recently there were surprisingly few studies on fear extinction during this period. Here we summarise the recent work in this area, focusing on the unique behavioural and neural characteristics of fear extinction in adolescent rodents, and humans where relevant. A prominent hypothesis posits that anxiety disorders peak during late childhood/adolescence due to the non-linear maturation of the fear inhibition neural circuitry. We discuss evidence that impaired extinction retention in adolescence is due to subregions of the medial prefrontal cortex and amygdala mediating fear inhibition being underactive while other subregions that mediate fear expression are overactive. We also review work on various interventions and surprising circumstances which enhance fear extinction in adolescence. This latter work revealed that the neural correlates of extinction in adolescence are different to that in younger and older animals even when extinction retention is not impaired. This growing body of work highlights that adolescence is a unique period of development for fear inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Energy efficient neural stimulation: coupling circuit design and membrane biophysics.

    Science.gov (United States)

    Foutz, Thomas J; Ackermann, D Michael; Kilgore, Kevin L; McIntyre, Cameron C

    2012-01-01

    The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.

  6. The neural substrates of infant sleep in rats.

    Directory of Open Access Journals (Sweden)

    Karl A E Karlsson

    2005-05-01

    Full Text Available Sleep is a poorly understood behavior that predominates during infancy but is studied almost exclusively in adults. One perceived impediment to investigations of sleep early in ontogeny is the absence of state-dependent neocortical activity. Nonetheless, in infant rats, sleep is reliably characterized by the presence of tonic (i.e., muscle atonia and phasic (i.e., myoclonic twitching components; the neural circuitry underlying these components, however, is unknown. Recently, we described a medullary inhibitory area (MIA in week-old rats that is necessary but not sufficient for the normal expression of atonia. Here we report that the infant MIA receives projections from areas containing neurons that exhibit state-dependent activity. Specifically, neurons within these areas, including the subcoeruleus (SubLC, pontis oralis (PO, and dorsolateral pontine tegmentum (DLPT, exhibit discharge profiles that suggest causal roles in the modulation of muscle tone and the production of myoclonic twitches. Indeed, lesions in the SubLC and PO decreased the expression of muscle atonia without affecting twitching (resulting in "REM sleep without atonia", whereas lesions of the DLPT increased the expression of atonia while decreasing the amount of twitching. Thus, the neural substrates of infant sleep are strikingly similar to those of adults, a surprising finding in light of theories that discount the contribution of supraspinal neural elements to sleep before the onset of state-dependent neocortical activity.

  7. Monitoring activity in neural circuits with genetically encoded indicators

    Directory of Open Access Journals (Sweden)

    Gerard Joseph Broussard

    2014-12-01

    Full Text Available Recent developments in genetically encoded indicators of neural activity (GINAs have greatly advanced the field of systems neuroscience. As they are encoded by DNA, GINAs can be targeted to genetically defined cellular populations. Combined with fluorescence microscopy, most notably multi-photon imaging, GINAs allow chronic simultaneous optical recordings from large populations of neurons or glial cells in awake, behaving mammals, particularly rodents. This large-scale recording of neural activity at multiple temporal and spatial scales has greatly advanced our understanding of the dynamics of neural circuitry underlying behavior—a critical first step toward understanding the complexities of brain function, such as sensorimotor integration and learning.Here, we summarize the recent development and applications of the major classes of GINAs. In particular, we take an in-depth look at the design of available GINA families with a particular focus on genetically encoded calcium indicators, sensors probing synaptic activity, and genetically encoded voltage indicators. Using the family of the genetically encoded calcium indicator GCaMP as an example, we review established sensor optimization pipelines. We also discuss practical considerations for end users of GINAs about experimental methods including approaches for gene delivery, imaging system requirements, and data analysis techniques. With the growing toolbox of GINAs and with new microscopy techniques pushing beyond their current limits, the age of light can finally achieve the goal of broad and dense sampling of neuronal activity across time and brain structures to obtain a dynamic picture of brain function.

  8. Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder

    Science.gov (United States)

    Morey, R A; Dunsmoor, J E; Haswell, C C; Brown, V M; Vora, A; Weiner, J; Stjepanovic, D; Wagner, H R; Brancu, Mira; Marx, Christine E; Naylor, Jennifer C; Van Voorhees, Elizabeth; Taber, Katherine H; Beckham, Jean C; Calhoun, Patrick S; Fairbank, John A; Szabo, Steven T; LaBar, K S

    2015-01-01

    Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (Pgeneralization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma. PMID:26670285

  9. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

    In contemporary consciousness studies the phenomenon of neural plasticity has received little attention despite the fact that neural plasticity is of still increased interest in neuroscience. We will, however, argue that neural plasticity could be of great importance to consciousness studies....... If consciousness is related to neural processes it seems, at least prima facie, that the ability of the neural structures to change should be reflected in a theory of this relationship "Neural plasticity" refers to the fact that the brain can change due to its own activity. The brain is not static but rather...... a dynamic entity, which physical structure changes according to its use and environment. This change may take the form of growth of new neurons, the creation of new networks and structures, and change within network structures, that is, changes in synaptic strengths. Plasticity raises questions about...

  10. Hafnium transistor design for neural interfacing.

    Science.gov (United States)

    Parent, David W; Basham, Eric J

    2008-01-01

    A design methodology is presented that uses the EKV model and the g(m)/I(D) biasing technique to design hafnium oxide field effect transistors that are suitable for neural recording circuitry. The DC gain of a common source amplifier is correlated to the structural properties of a Field Effect Transistor (FET) and a Metal Insulator Semiconductor (MIS) capacitor. This approach allows a transistor designer to use a design flow that starts with simple and intuitive 1-D equations for gain that can be verified in 1-D MIS capacitor TCAD simulations, before final TCAD process verification of transistor properties. The DC gain of a common source amplifier is optimized by using fast 1-D simulations and using slower, complex 2-D simulations only for verification. The 1-D equations are used to show that the increased dielectric constant of hafnium oxide allows a higher DC gain for a given oxide thickness. An additional benefit is that the MIS capacitor can be employed to test additional performance parameters important to an open gate transistor such as dielectric stability and ionic penetration.

  11. Language evolution: neural homologies and neuroinformatics.

    Science.gov (United States)

    Arbib, Michael; Bota, Mihail

    2003-11-01

    This paper contributes to neurolinguistics by grounding an evolutionary account of the readiness of the human brain for language in the search for homologies between different cortical areas in macaque and human. We consider two hypotheses for this grounding, that of Aboitiz and Garci;a [Brain Res. Rev. 25 (1997) 381] and the Mirror System Hypothesis of Rizzolatti and Arbib [Trends Neurosci. 21 (1998) 188] and note the promise of computational modeling of neural circuitry of the macaque and its linkage to analysis of human brain imaging data. In addition to the functional differences between the two hypotheses, problems arise because they are grounded in different cortical maps of the macaque brain. In order to address these divergences, we have developed several neuroinformatics tools included in an on-line knowledge management system, the NeuroHomology Database, which is equipped with inference engines both to relate and translate information across equivalent cortical maps and to evaluate degrees of homology for brain regions of interest in different species.

  12. EDITORIAL: Special issue on applied neurodynamics: from neural dynamics to neural engineering Special issue on applied neurodynamics: from neural dynamics to neural engineering

    Science.gov (United States)

    Chiel, Hillel J.; Thomas, Peter J.

    2011-12-01

    in part on his own work in this area. This is a very small glimpse of a much larger literature; these mathematical themes recur throughout this issue. Practitioners of neural engineering who want to explore the language and role of dynamics further can find accessible introductions to the key ideas in works such as Strogatz (1994) and Izhikevich (2006). In this special issue of Journal of Neural Engineering, we provide a sample of the vigor and excitement of the recent developments in the applications of nonlinear dynamical systems theory to the understanding and control of the nervous system. Four of the papers demonstrate the power of dynamical systems theory to analyze and understand neural systems, both in isolation and within a neuromechanical context (Coggan et al 2011, Nadim et al 2011, Spardy et al 2011a, 2011b). One paper focuses on the importance of noise and delay in dynamical systems for control (Milton 2011). Two papers focus on the dynamics of ion channels—in one paper, new approaches for estimating their parameters are described (Meng et al 2011), and in a second, the time courses of sodium ion channels are used to understand conduction block due to high-frequency stimulation (Ackermann et al 2011). Two papers focus on the use of optimal control theory to develop approaches for understanding (deWolf and Eliasmith 2011) and controlling (Nabi and Moehlis 2011) the nervous system. Finally, two papers begin to explore longer time scale neural dynamics through a combination of modeling and experiments, examining how animals learn to reduce the time required to forage for food at multiple sites (de Jong et al 2011), and how the dynamics of the respiratory system change with development (Fietkiewicz et al 2011). The first four papers of this special issue illustrate the use of dynamical systems theory to analyze and understand neural circuitry and neuromechanical systems. The first of these papers uses the phase response curve (PRC) of an oscillator, which

  13. Fuzzy and neural control

    Science.gov (United States)

    Berenji, Hamid R.

    1992-01-01

    Fuzzy logic and neural networks provide new methods for designing control systems. Fuzzy logic controllers do not require a complete analytical model of a dynamic system and can provide knowledge-based heuristic controllers for ill-defined and complex systems. Neural networks can be used for learning control. In this chapter, we discuss hybrid methods using fuzzy logic and neural networks which can start with an approximate control knowledge base and refine it through reinforcement learning.

  14. Common features of neural activity during singing and sleep periods in a basal ganglia nucleus critical for vocal learning in a juvenile songbird.

    Directory of Open Access Journals (Sweden)

    Shin Yanagihara

    Full Text Available Reactivations of waking experiences during sleep have been considered fundamental neural processes for memory consolidation. In songbirds, evidence suggests the importance of sleep-related neuronal activity in song system motor pathway nuclei for both juvenile vocal learning and maintenance of adult song. Like those in singing motor nuclei, neurons in the basal ganglia nucleus Area X, part of the basal ganglia-thalamocortical circuit essential for vocal plasticity, exhibit singing-related activity. It is unclear, however, whether Area X neurons show any distinctive spiking activity during sleep similar to that during singing. Here we demonstrate that, during sleep, Area X pallidal neurons exhibit phasic spiking activity, which shares some firing properties with activity during singing. Shorter interspike intervals that almost exclusively occurred during singing in awake periods were also observed during sleep. The level of firing variability was consistently higher during singing and sleep than during awake non-singing states. Moreover, deceleration of firing rate, which is considered to be an important firing property for transmitting signals from Area X to the thalamic nucleus DLM, was observed mainly during sleep as well as during singing. These results suggest that songbird basal ganglia circuitry may be involved in the off-line processing potentially critical for vocal learning during sensorimotor learning phase.

  15. What Is Neural Plasticity?

    Science.gov (United States)

    von Bernhardi, Rommy; Bernhardi, Laura Eugenín-von; Eugenín, Jaime

    2017-01-01

    "Neural plasticity" refers to the capacity of the nervous system to modify itself, functionally and structurally, in response to experience and injury. As the various chapters in this volume show, plasticity is a key component of neural development and normal functioning of the nervous system, as well as a response to the changing environment, aging, or pathological insult. This chapter discusses how plasticity is necessary not only for neural networks to acquire new functional properties, but also for them to remain robust and stable. The article also reviews the seminal proposals developed over the years that have driven experiments and strongly influenced concepts of neural plasticity.

  16. Neural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  17. A neural flow estimator

    DEFF Research Database (Denmark)

    Jørgensen, Ivan Harald Holger; Bogason, Gudmundur; Bruun, Erik

    1995-01-01

    is implemented using switched-current technique and is capable of estimating flow in the μl/s range. The neural estimator is built around a multiplierless neural network, containing 96 synaptic weights which are updated using the LMS1-algorithm. An experimental chip has been designed that operates at 5 V......This paper proposes a new way to estimate the flow in a micromechanical flow channel. A neural network is used to estimate the delay of random temperature fluctuations induced in a fluid. The design and implementation of a hardware efficient neural flow estimator is described. The system...

  18. Initiation and modulation of locomotor circuitry output with multisite transcutaneous electrical stimulation of the spinal cord in noninjured humans.

    Science.gov (United States)

    Gerasimenko, Yury; Gorodnichev, Ruslan; Puhov, Aleksandr; Moshonkina, Tatiana; Savochin, Aleksandr; Selionov, Victor; Roy, Roland R; Lu, Daniel C; Edgerton, V Reggie

    2015-02-01

    The mammalian lumbar spinal cord has the capability to generate locomotor activity in the absence of input from the brain. Previously, we reported that transcutaneous electrical stimulation of the spinal cord at vertebral level T11 can activate the locomotor circuitry in noninjured subjects when their legs are placed in a gravity-neutral position (Gorodnichev RM, Pivovarova EA, Pukhov A, Moiseev SA, Savokhin AA, Moshonkina TR, Shcherbakova NA, Kilimnik VA, Selionov VA, Kozlovskaia IB, Edgerton VR, Gerasimenko IU. Fiziol Cheloveka 38: 46-56, 2012). In the present study we hypothesized that stimulating multiple spinal sites and therefore unique combinations of networks converging on postural and locomotor lumbosacral networks would be more effective in inducing more robust locomotor behavior and more selective control than stimulation of more restricted networks. We demonstrate that simultaneous stimulation at the cervical, thoracic, and lumbar levels induced coordinated stepping movements with a greater range of motion at multiple joints in five of six noninjured subjects. We show that the addition of stimulation at L1 and/or at C5 to stimulation at T11 immediately resulted in enhancing the kinematics and interlimb coordination as well as the EMG patterns in proximal and distal leg muscles. Sequential cessation of stimulation at C5 and then at L1 resulted in a progressive degradation of the stepping pattern. The synergistic and interactive effects of transcutaneous stimulation suggest a multisegmental convergence of descending and ascending, and most likely propriospinal, influences on the spinal neuronal circuitries associated with locomotor activity. The potential impact of using multisite spinal cord stimulation as a strategy to neuromodulate the spinal circuitry has significant implications in furthering our understanding of the mechanisms controlling posture and locomotion and for regaining significant sensorimotor function even after a severe spinal cord

  19. Role of SDF1/CXCR4 Interaction in Experimental Hemiplegic Models with Neural Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Noboru Suzuki

    2012-02-01

    Full Text Available Much attention has been focused on neural cell transplantation because of its promising clinical applications. We have reported that embryonic stem (ES cell derived neural stem/progenitor cell transplantation significantly improved motor functions in a hemiplegic mouse model. It is important to understand the molecular mechanisms governing neural regeneration of the damaged motor cortex after the transplantation. Recent investigations disclosed that chemokines participated in the regulation of migration and maturation of neural cell grafts. In this review, we summarize the involvement of inflammatory chemokines including stromal cell derived factor 1 (SDF1 in neural regeneration after ES cell derived neural stem/progenitor cell transplantation in mouse stroke models.

  20. Survey on Neural Networks Used for Medical Image Processing.

    Science.gov (United States)

    Shi, Zhenghao; He, Lifeng; Suzuki, Kenji; Nakamura, Tsuyoshi; Itoh, Hidenori

    2009-02-01

    This paper aims to present a review of neural networks used in medical image processing. We classify neural networks by its processing goals and the nature of medical images. Main contributions, advantages, and drawbacks of the methods are mentioned in the paper. Problematic issues of neural network application for medical image processing and an outlook for the future research are also discussed. By this survey, we try to answer the following two important questions: (1) What are the major applications of neural networks in medical image processing now and in the nearby future? (2) What are the major strengths and weakness of applying neural networks for solving medical image processing tasks? We believe that this would be very helpful researchers who are involved in medical image processing with neural network techniques.

  1. [Mechanism of neural plasticity of acupuncture on chronic migraine].

    Science.gov (United States)

    Xu, Xiaobai; Liu, Lu; Zhao, Luopeng; Qu, Zhengyang; Zhu, Yupu; Zhang, Yajie; Wang, Linpeng

    2017-10-12

    Chronic migraine is one of neurological disorders with high rate of disability, but sufficient attention has not been paid in this field. A large number of clinical studies have shown traditional Chinese acupuncture is a kind of effective treatment with less side effects. Through the analysis of literature regarding acupuncture and migraine published from 1981 to 2017 in CNKI and PubMed databases, the mechanism of neural plasticity of acupuncture on chronic migraine was explored. It was believed the progress of chronic migraine involved the changes of neural plasticity in neural structure and function, and the neural plasticity related with neural sensitization during the process of chronic migraine was discussed from three aspects of electrophysiology, molecular chemistry and radiography. Acupuncture could treat and prevent chronic migraine via the mechanism of neural plasticity, but there was no related literature, hindering the further spreading and development of acupuncture for chronic migraine.

  2. Recent advances in neural recording microsystems.

    Science.gov (United States)

    Gosselin, Benoit

    2011-01-01

    The accelerating pace of research in neuroscience has created a considerable demand for neural interfacing microsystems capable of monitoring the activity of large groups of neurons. These emerging tools have revealed a tremendous potential for the advancement of knowledge in brain research and for the development of useful clinical applications. They can extract the relevant control signals directly from the brain enabling individuals with severe disabilities to communicate their intentions to other devices, like computers or various prostheses. Such microsystems are self-contained devices composed of a neural probe attached with an integrated circuit for extracting neural signals from multiple channels, and transferring the data outside the body. The greatest challenge facing development of such emerging devices into viable clinical systems involves addressing their small form factor and low-power consumption constraints, while providing superior resolution. In this paper, we survey the recent progress in the design and the implementation of multi-channel neural recording Microsystems, with particular emphasis on the design of recording and telemetry electronics. An overview of the numerous neural signal modalities is given and the existing microsystem topologies are covered. We present energy-efficient sensory circuits to retrieve weak signals from neural probes and we compare them. We cover data management and smart power scheduling approaches, and we review advances in low-power telemetry. Finally, we conclude by summarizing the remaining challenges and by highlighting the emerging trends in the field.

  3. Recent Advances in Neural Recording Microsystems

    Directory of Open Access Journals (Sweden)

    Benoit Gosselin

    2011-04-01

    Full Text Available The accelerating pace of research in neuroscience has created a considerable demand for neural interfacing microsystems capable of monitoring the activity of large groups of neurons. These emerging tools have revealed a tremendous potential for the advancement of knowledge in brain research and for the development of useful clinical applications. They can extract the relevant control signals directly from the brain enabling individuals with severe disabilities to communicate their intentions to other devices, like computers or various prostheses. Such microsystems are self-contained devices composed of a neural probe attached with an integrated circuit for extracting neural signals from multiple channels, and transferring the data outside the body. The greatest challenge facing development of such emerging devices into viable clinical systems involves addressing their small form factor and low-power consumption constraints, while providing superior resolution. In this paper, we survey the recent progress in the design and the implementation of multi-channel neural recording Microsystems, with particular emphasis on the design of recording and telemetry electronics. An overview of the numerous neural signal modalities is given and the existing microsystem topologies are covered. We present energy-efficient sensory circuits to retrieve weak signals from neural probes and we compare them. We cover data management and smart power scheduling approaches, and we review advances in low-power telemetry. Finally, we conclude by summarizing the remaining challenges and by highlighting the emerging trends in the field.

  4. Neural Networks: Implementations and Applications

    NARCIS (Netherlands)

    Vonk, E.; Veelenturf, L.P.J.; Jain, L.C.

    1996-01-01

    Artificial neural networks, also called neural networks, have been used successfully in many fields including engineering, science and business. This paper presents the implementation of several neural network simulators and their applications in character recognition and other engineering areas

  5. Neural Correlates of Predictive Saccades.

    Science.gov (United States)

    Lee, Stephen M; Peltsch, Alicia; Kilmade, Maureen; Brien, Donald C; Coe, Brian C; Johnsrude, Ingrid S; Munoz, Douglas P

    2016-08-01

    Every day we generate motor responses that are timed with external cues. This phenomenon of sensorimotor synchronization has been simplified and studied extensively using finger tapping sequences that are executed in synchrony with auditory stimuli. The predictive saccade paradigm closely resembles the finger tapping task. In this paradigm, participants follow a visual target that "steps" between two fixed locations on a visual screen at predictable ISIs. Eventually, the time from target appearance to saccade initiation (i.e., saccadic RT) becomes predictive with values nearing 0 msec. Unlike the finger tapping literature, neural control of predictive behavior described within the eye movement literature has not been well established and is inconsistent, especially between neuroimaging and patient lesion studies. To resolve these discrepancies, we used fMRI to investigate the neural correlates of predictive saccades by contrasting brain areas involved with behavior generated from the predictive saccade task with behavior generated from a reactive saccade task (saccades are generated toward targets that are unpredictably timed). We observed striking differences in neural recruitment between reactive and predictive conditions: Reactive saccades recruited oculomotor structures, as predicted, whereas predictive saccades recruited brain structures that support timing in motor responses, such as the crus I of the cerebellum, and structures commonly associated with the default mode network. Therefore, our results were more consistent with those found in the finger tapping literature.

  6. Secondary Sensory Area SII is Crucially Involved in the Preparation of Familiar Movements Compared to Movements Never Made Before

    NARCIS (Netherlands)

    Beudel, M.; Zijlstra, S.; Mulder, Th.; Zijdewind, I.; de Jong, B. M.

    Secondary sensorimotor regions are involved in sensorimotor integration and movement preparation. These regions take part in parietal-premotor circuitry that is not only active during motor execution but also during movement observation and imagery. This activation particularly occurs when observed

  7. Working memory circuitry in schizophrenia shows widespread cortical inefficiency and compensation.

    Science.gov (United States)

    Kim, Miyoung A; Tura, Emanuela; Potkin, Steven G; Fallon, James H; Manoach, Dara S; Calhoun, Vince D; Turner, Jessica A

    2010-03-01

    Working memory studies in schizophrenia (SZ), using functional magnetic resonance imaging (fMRI) and univariate analyses, have led to observations of hypo- or hyperactivation of discrete cortical regions and subsequent interpretations (e.g. neural inefficiencies). We employed a data-driven, multivariate analysis to identify the patterns of brain-behavior relationships in SZ during working memory. fMRI scans were collected from 13 SZ and 18 healthy control (HC) participants performing a modified Sternberg item recognition paradigm with three memory loads. We applied partial least squares analysis (PLS) to assess brain activation during the task both alone and with behavioral measures (accuracy and response time, RT) as covariates. While the HC primary pattern was not affected by increasing load demands, SZ participants showed an exaggerated change in the Blood Oxygenation Level Dependent (BOLD) signal from the low to moderate memory load conditions and subsequent decrease in the greatest memory load, in frontal, motor, parietal and subcortical areas. With behavioral covariates, the separate groups identified distinct brain-behavior relationships and circuits. Increased activation of the middle temporal gyrus was associated with greater accuracy and faster RT only in SZ. The inverted U-shaped curves in the SZ BOLD signal in the same areas that show flat activation in the HC data indicate widespread neural inefficiency in working memory in SZ. While both groups performed the task with similar levels of accuracy, participants with schizophrenia show a compensatory network of different sub-regions of the prefrontal cortex, parietal lobule, and the temporal gyri in this working memory task. (c) 2009 Elsevier B.V. All rights reserved.

  8. Spiraling dopaminergic circuitry from the ventral striatum to dorsal striatum is an effective feed-forward loop.

    Science.gov (United States)

    Ikeda, H; Saigusa, T; Kamei, J; Koshikawa, N; Cools, A R

    2013-06-25

    Central dopamine systems are key players in the cerebral organization of behavior and in various neurological and psychiatric diseases. We demonstrate the presence of a neurochemical feed-forward loop characterized by region-specific changes in dopamine efflux in serially connected striatal regions, providing evidence in favor of the existence of so-called spiraling striato-nigro-striatal connections. Using in vivo microdialysis of rats, we show that simultaneous stimulation of dopamine D1 and D2 receptors in the accumbal shell decreased dorsal striatal dopamine efflux via a direct or indirect feed-forward loop involving shell, core, ventrolateral and dorsal part of the striatum: simultaneous stimulation of dopamine D1 and D2 receptors in the shell decreased dopamine efflux in the core; flupenthixol-induced inhibition of dopamine D1 and D2 receptors in the core increased dopamine efflux in the ventrolateral part of the striatum, and simultaneous stimulation of dopamine D1 and D2 receptors in the ventrolateral part of the striatum decreased dopamine efflux in the dorsal part of the striatum. Finally, simultaneous stimulation of dopamine D1 and D2 receptors in the shell decreased dopamine efflux in the dorsal part of the striatum. Thus, distinct striatal regions act also in series, providing a better understanding of the neural mechanisms underlying dopamine-dependent behaviors and the progression of dopamine-dependent disorders such as depression, schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli.

    Science.gov (United States)

    Pannuri, Archana; Vakulskas, Christopher A; Zere, Tesfalem; McGibbon, Louise C; Edwards, Adrianne N; Georgellis, Dimitris; Babitzke, Paul; Romeo, Tony

    2016-11-01

    Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates csrB and csrC (csrB/C) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits csrB/C transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A crp deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of csrB-lacZ and csrC-lacZ transcriptional fusions, although modest stimulation of CsrB/C turnover by the crp deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the csrC promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites. In vitro transcription-translation experiments confirmed direct repression of csrC-lacZ expression by cAMP-CRP. In contrast, cAMP-CRP effects on csrB transcription may be mediated indirectly, as it bound nonspecifically to csrB DNA. In the reciprocal direction, CsrA bound to crp mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status. Csr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of Escherichia coli use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower

  10. Neural tube morphogenesis in synthetic 3D microenvironments

    National Research Council Canada - National Science Library

    Ranga, Aian; Girgin, Mehmet; Meinhardt, Anea; Eberle, Dominic; Caiazzo, Massimiliano; Tanaka, Elly M; Lutolf, Matthias P

    2016-01-01

    .... We demonstrate how key ECM parameters are involved in specifying cytoskeleton-mediated symmetry-breaking events that ultimately lead to neural tube-like patterning along the dorsal-ventral (DV) axis...

  11. Alexia and the Neural Basis of Reading.

    Science.gov (United States)

    Benson, D. Frank

    1984-01-01

    The historical background of alexia (loss or impairment of the ability to comprehend written or printed language based on damage to the brain) is reviewed, classification and symptomatology considered, theories on the involvement of right hemisphere reading are noted, and the neural basis of reading is postulated. (CL)

  12. Review: Neural correlates of consciousness | Negrao | African ...

    African Journals Online (AJOL)

    A basic understanding of consciousness and its neural correlates is of major importance for all clinicians, especially those involved with patients with altered states of consciousness. In this paper it is shown that consciousness is dependent on the brainstem and thalamus for arousal; that basic cognition is supported by ...

  13. Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry. Implications for drug addiction, sleep and pain

    Science.gov (United States)

    Ferré, S.; Diamond, I.; Goldberg, S.R.; Yao, L.; Hourani, S.M.O.; Huang, Z.L.; Urade, Y.; Kitchen, I.

    2007-01-01

    Adenosine A2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A2A receptors. A2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A2A receptor knockout mice suggest that A2A receptor antagonists might have some therapeutic potential in pain states, in particular where

  14. Critical Branching Neural Networks

    Science.gov (United States)

    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…

  15. Kunstige neurale net

    DEFF Research Database (Denmark)

    Hørning, Annette

    1994-01-01

    Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse.......Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse....

  16. Neural tube closure: cellular, molecular and biomechanical mechanisms.

    Science.gov (United States)

    Nikolopoulou, Evanthia; Galea, Gabriel L; Rolo, Ana; Greene, Nicholas D E; Copp, Andrew J

    2017-02-15

    Neural tube closure has been studied for many decades, across a range of vertebrates, as a paradigm of embryonic morphogenesis. Neurulation is of particular interest in view of the severe congenital malformations - 'neural tube defects' - that result when closure fails. The process of neural tube closure is complex and involves cellular events such as convergent extension, apical constriction and interkinetic nuclear migration, as well as precise molecular control via the non-canonical Wnt/planar cell polarity pathway, Shh/BMP signalling, and the transcription factors Grhl2/3, Pax3, Cdx2 and Zic2. More recently, biomechanical inputs into neural tube morphogenesis have also been identified. Here, we review these cellular, molecular and biomechanical mechanisms involved in neural tube closure, based on studies of various vertebrate species, focusing on the most recent advances in the field. © 2017. Published by The Company of Biologists Ltd.

  17. The neural circuit basis of learning

    Science.gov (United States)

    Patrick, Kaifosh William John

    The astounding capacity for learning ranks among the nervous system's most impressive features. This thesis comprises studies employing varied approaches to improve understanding, at the level of neural circuits, of the brain's capacity for learning. The first part of the thesis contains investigations of hippocampal circuitry -- both theoretical work and experimental work in the mouse Mus musculus -- as a model system for declarative memory. To begin, Chapter 2 presents a theory of hippocampal memory storage and retrieval that reflects nonlinear dendritic processing within hippocampal pyramidal neurons. As a prelude to the experimental work that comprises the remainder of this part, Chapter 3 describes an open source software platform that we have developed for analysis of data acquired with in vivo Ca2+ imaging, the main experimental technique used throughout the remainder of this part of the thesis. As a first application of this technique, Chapter 4 characterizes the content of signaling at synapses between GABAergic neurons of the medial septum and interneurons in stratum oriens of hippocampal area CA1. Chapter 5 then combines these techniques with optogenetic, pharmacogenetic, and pharmacological manipulations to uncover inhibitory circuit mechanisms underlying fear learning. The second part of this thesis focuses on the cerebellum-like electrosensory lobe in the weakly electric mormyrid fish Gnathonemus petersii, as a model system for non-declarative memory. In Chapter 6, we study how short-duration EOD motor commands are recoded into a complex temporal basis in the granule cell layer, which can be used to cancel Purkinje-like cell firing to the longer duration and temporally varying EOD-driven sensory responses. In Chapter 7, we consider not only the temporal aspects of the granule cell code, but also the encoding of body position provided from proprioceptive and efference copy sources. Together these studies clarify how the cerebellum-like circuitry of the

  18. Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4.

    Science.gov (United States)

    Stice, Eric; Yokum, Sonja; Bohon, Cara; Marti, Nate; Smolen, Andrew

    2010-05-01

    To determine whether responsivity of reward circuitry to food predicts future increases in body mass and whether polymorphisms in DRD2 and DRD4 moderate these relations. The functional magnetic resonance imaging (fMRI) paradigm investigated blood oxygen level dependent activation in response to imagined intake of palatable foods, unpalatable foods, and glasses of water shown in pictures. DNA was extracted from saliva samples using standard salting-out and solvent precipitation methods. Forty-four adolescent female high school students ranging from lean to obese. Future increases in body mass index (BMI). Weaker activation of the frontal operculum, lateral orbitofrontal cortex, and striatum in response to imagined intake of palatable foods, versus imagined intake of unpalatable foods or water, predicted future increases in body mass for those with the DRD2 TaqIA A1 allele or the DRD4-7R allele. Data also suggest that for those lacking these alleles, greater responsivity of these food reward regions predicted future increases in body mass. This novel prospective fMRI study indicates that responsivity of reward circuitry to food increases risk for future weight gain, but that genes that impact dopamine signaling capacity moderate the predictive effects, suggesting two qualitatively distinct pathways to unhealthy weight gain based on genetic risk. 2010 Elsevier Inc. All rights reserved.

  19. Positive autoregulation of cI is a dispensable feature of the phage lambda gene regulatory circuitry.

    Science.gov (United States)

    Michalowski, Christine B; Little, John W

    2005-09-01

    Complex gene regulatory circuits contain many features that are likely to contribute to their operation. It is unclear, however, whether all these features are necessary for proper circuit behavior or whether certain ones are refinements that make the circuit work better but are dispensable for qualitatively normal behavior. We have addressed this question using the phage lambda regulatory circuit, which can persist in two stable states, the lytic state and the lysogenic state. In the lysogenic state, the CI repressor positively regulates its own expression by stimulating transcription from the P(RM) promoter. We tested whether this feature is an essential part of the regulatory circuitry. Several phages with a cI mutation preventing positive autoregulation and an up mutation in the P(RM) promoter showed near-normal behavior. We conclude that positive autoregulation is not necessary for proper operation of the lambda circuitry and speculate that it serves a partially redundant function of stabilizing a bistable circuit, a form of redundancy we term "circuit-level redundancy." We discuss our findings in the context of a two-stage model for evolution and elaboration of regulatory circuits from simpler to more complex forms.

  20. Top-down gain control of the auditory space map by gaze control circuitry in the barn owl.

    Science.gov (United States)

    Winkowski, Daniel E; Knudsen, Eric I

    2006-01-19

    High-level circuits in the brain that control the direction of gaze are intimately linked with the control of visual spatial attention. Immediately before an animal directs its gaze towards a stimulus, both psychophysical sensitivity to that visual stimulus and the responsiveness of high-order neurons in the cerebral cortex that represent the stimulus increase dramatically. Equivalent effects on behavioural sensitivity and neuronal responsiveness to visual stimuli result from focal electrical microstimulation of gaze control centres in monkeys. Whether the gaze control system modulates neuronal responsiveness in sensory modalities other than vision is unknown. Here we show that electrical microstimulation applied to gaze control circuitry in the forebrain of barn owls regulates the gain of midbrain auditory responses in an attention-like manner. When the forebrain circuit was activated, midbrain responses to auditory stimuli at the location encoded by the forebrain site were enhanced and spatial selectivity was sharpened. The same stimulation suppressed responses to auditory stimuli represented at other locations in the midbrain map. Such space-specific, top-down regulation of auditory responses by gaze control circuitry in the barn owl suggests that the central nervous system uses a common strategy for dynamically regulating sensory gain that applies across modalities, brain areas and classes of vertebrate species. This approach provides a path for discovering mechanisms that underlie top-down gain control in the central nervous system.

  1. Processing of Multi-dimensional Sensorimotor Information in the Spinal and Cerebellar Neuronal Circuitry: A New Hypothesis

    Science.gov (United States)

    Spanne, Anton; Jörntell, Henrik

    2013-01-01

    Why are sensory signals and motor command signals combined in the neurons of origin of the spinocerebellar pathways and why are the granule cells that receive this input thresholded with respect to their spike output? In this paper, we synthesize a number of findings into a new hypothesis for how the spinocerebellar systems and the cerebellar cortex can interact to support coordination of our multi-segmented limbs and bodies. A central idea is that recombination of the signals available to the spinocerebellar neurons can be used to approximate a wide array of functions including the spatial and temporal dependencies between limb segments, i.e. information that is necessary in order to achieve coordination. We find that random recombination of sensory and motor signals is not a good strategy since, surprisingly, the number of granule cells severely limits the number of recombinations that can be represented within the cerebellum. Instead, we propose that the spinal circuitry provides useful recombinations, which can be described as linear projections through aspects of the multi-dimensional sensorimotor input space. Granule cells, potentially with the aid of differentiated thresholding from Golgi cells, enhance the utility of these projections by allowing the Purkinje cell to establish piecewise-linear approximations of non-linear functions. Our hypothesis provides a novel view on the function of the spinal circuitry and cerebellar granule layer, illustrating how the coordinating functions of the cerebellum can be crucially supported by the recombinations performed by the neurons of the spinocerebellar systems. PMID:23516353

  2. Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in iv mice.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Goto

    Full Text Available Although left-right (L-R asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.

  3. FOXA and master transcription factors recruit Mediator and Cohesin to the core transcriptional regulatory circuitry of cancer cells

    Science.gov (United States)

    Fournier, Michèle; Bourriquen, Gaëlle; Lamaze, Fabien C.; Côté, Maxime C.; Fournier, Éric; Joly-Beauparlant, Charles; Caron, Vicky; Gobeil, Stéphane; Droit, Arnaud; Bilodeau, Steve

    2016-10-01

    Controlling the transcriptional program is essential to maintain the identity and the biological functions of a cell. The Mediator and Cohesin complexes have been established as central cofactors controlling the transcriptional program in normal cells. However, the distribution, recruitment and importance of these complexes in cancer cells have not been fully investigated. Here we show that FOXA and master transcription factors are part of the core transcriptional regulatory circuitry of cancer cells and are essential to recruit M ediator and Cohesin. Indeed, Mediator and Cohesin occupied the enhancer and promoter regions of actively transcribed genes and maintained the proliferation and colony forming potential. Through integration of publically available ChIP-Seq datasets, we predicted the core transcriptional regulatory circuitry of each cancer cell. Unexpectedly, for all cells investigated, the pioneer transcription factors FOXA1 and/or FOXA2 were identified in addition to cell-specific master transcription factors. Loss of both types of transcription factors phenocopied the loss of Mediator and Cohesin. Lastly, the master and pioneer transcription factors were essential to recruit Mediator and Cohesin to regulatory regions of actively transcribed genes. Our study proposes that maintenance of the cancer cell state is dependent on recruitment of Mediator and Cohesin through FOXA and master transcription factors.

  4. EDITORIAL: Focus on the neural interface Focus on the neural interface

    Science.gov (United States)

    Durand, Dominique M.

    2009-10-01

    they can fail to record reliably neural signals for long periods of time. McConnell et al show that by measuring the impedance of the tissue, one can evaluate the extent of the tissue response to the presence of the electrode. Another problem with the neural interface is the mismatch of the mechanical properties between electrode and tissue. Basinger et al use finite element modeling to analyze this mismatch in retinal prostheses and guide the design of new implantable devices. Electrical stimulation has been the method of choice to activate externally the nervous system. However, Zhang et al show that a novel dual hybrid device integrating electrical and optical stimulation can provide an effective interface for simultaneous recording and stimulation. By interfacing an EMG recording system and a movement detection system, Johnson and Fuglevand develop a model capable of predicting muscle activity during movement that could be important for the development of motor prostheses. Sensory restoration is another unsolved problem in neural prostheses. By developing a novel interface between the dorsal root ganglia and electrodes arrays, Gaunt et al show that it is possible to recruit afferent fibers for sensory substitution. Finally, by interfacing directly with muscles, Jung and colleagues show that stimulation of muscles involved in locomotion following spinal cord damage in rats can provide an effective treatment modality for incomplete spinal cord injury. This series of articles clearly shows that the interface is indeed one of the keys to successful therapeutic neural devices. The next Neural Interfaces Conference will take place in Los Angeles, CA in June 2010 and one can expect to see new developments in neural engineering obtained by focusing on the neural interface.

  5. Integrating Neural Circuits Controlling Female Sexual Behavior

    Directory of Open Access Journals (Sweden)

    Paul E. Micevych

    2017-06-01

    Full Text Available The hypothalamus is most often associated with innate behaviors such as is hunger, thirst and sex. While the expression of these behaviors important for survival of the individual or the species is nested within the hypothalamus, the desire (i.e., motivation for them is centered within the mesolimbic reward circuitry. In this review, we will use female sexual behavior as a model to examine the interaction of these circuits. We will examine the evidence for a hypothalamic circuit that regulates consummatory aspects of reproductive behavior, i.e., lordosis behavior, a measure of sexual receptivity that involves estradiol membrane-initiated signaling in the arcuate nucleus (ARH, activating β-endorphin projections to the medial preoptic nucleus (MPN, which in turn modulate ventromedial hypothalamic nucleus (VMH activity—the common output from the hypothalamus. Estradiol modulates not only a series of neuropeptides, transmitters and receptors but induces dendritic spines that are for estrogenic induction of lordosis behavior. Simultaneously, in the nucleus accumbens of the mesolimbic system, the mating experience produces long term changes in dopamine signaling and structure. Sexual experience sensitizes the response of nucleus accumbens neurons to dopamine signaling through the induction of a long lasting early immediate gene. While estrogen alone increases spines in the ARH, sexual experience increases dendritic spine density in the nucleus accumbens. These two circuits appear to converge onto the medial preoptic area where there is a reciprocal influence of motivational circuits on consummatory behavior and vice versa. While it has not been formally demonstrated in the human, such circuitry is generally highly conserved and thus, understanding the anatomy, neurochemistry and physiology can provide useful insight into the motivation for sexual behavior and other innate behaviors in humans.

  6. Design of Robust Neural Network Classifiers

    DEFF Research Database (Denmark)

    Larsen, Jan; Andersen, Lars Nonboe; Hintz-Madsen, Mads

    1998-01-01

    This paper addresses a new framework for designing robust neural network classifiers. The network is optimized using the maximum a posteriori technique, i.e., the cost function is the sum of the log-likelihood and a regularization term (prior). In order to perform robust classification, we present...... a modified likelihood function which incorporates the potential risk of outliers in the data. This leads to the introduction of a new parameter, the outlier probability. Designing the neural classifier involves optimization of network weights as well as outlier probability and regularization parameters. We...

  7. Electronic device aspects of neural network memories

    Science.gov (United States)

    Lambe, J.; Moopenn, A.; Thakoor, A. P.

    1985-01-01

    The basic issues related to the electronic implementation of the neural network model (NNM) for content addressable memories are examined. A brief introduction to the principles of the NNM is followed by an analysis of the information storage of the neural network in the form of a binary connection matrix and the recall capability of such matrix memories based on a hardware simulation study. In addition, materials and device architecture issues involved in the future realization of such networks in VLSI-compatible ultrahigh-density memories are considered. A possible space application of such devices would be in the area of large-scale information storage without mechanical devices.

  8. Using Neural Networks in Decision Making for a Reconfigurable Electro Mechanical Actuator (EMA)

    Science.gov (United States)

    Latino, Carl D.

    2001-01-01

    The objectives of this project were to demonstrate applicability and advantages of a neural network approach for evaluating the performance of an electro-mechanical actuator (EMA). The EMA in question was intended for the X-37 Advanced Technology Vehicle. It will have redundant components for safety and reliability. The neural networks for this application are to monitor the operation of the redundant electronics that control the actuator in real time and decide on the operating configuration. The system we proposed consists of the actuator, sensors, control circuitry and dedicated (embedded) processors. The main purpose of the study was to develop suitable hardware and neural network capable of allowing real time reconfiguration decisions to be made. This approach was to be compared to other methods such as fuzzy logic and knowledge based systems considered for the same application. Over the course of the project a more general objective was the identification of the other neural network applications and the education of interested NASA personnel on the topic of Neural Networks.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. Dynamics of neural cryptography.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

    2007-05-01

    Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

  12. Neural mechanisms controlling seasonal reproduction: principles derived from the sheep model and its comparison with hamsters.

    Science.gov (United States)

    Weems, Peyton W; Goodman, Robert L; Lehman, Michael N

    2015-04-01

    Seasonal reproduction is a common adaptive strategy among mammals that allows for breeding to occur at times of the year when it is most advantageous for the subsequent survival and growth of offspring. A major mechanism responsible for seasonal reproduction is a striking increase in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the negative feedback effects of estradiol. The neural and neuroendocrine circuitry responsible for mammalian seasonal reproduction has been primarily studied in three animal models: the sheep, and two species of hamsters. In this review, we first describe the afferent signals, neural circuitry and transmitters/peptides responsible for seasonal reproductive transitions in sheep, and then compare these mechanisms with those derived from studies in hamsters. The results suggest common principles as well as differences in the role of specific brain nuclei and neuropeptides, including that of kisspeptin cells of the hypothalamic arcuate nucleus, in regulating seasonal reproduction among mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The Neural Correlates of “Food Addiction”

    Science.gov (United States)

    Gearhardt, Ashley N.; Yokum, Sonja; Orr, Patrick T.; Stice, Eric; Corbin, William R.; Brownell, Kelly D.

    2014-01-01

    Context Research has implicated an addictive process in the development and maintenance of obesity. Although parallels in neural functioning between obesity and substance dependence have been found, no studies have examined the neural correlates of addictive-like eating behavior. Objective To test the hypothesis that elevated “food addiction” scores are associated with similar patterns of neural activation as substance dependence. Design Between-Subjects fMRI study. Participants Forty-eight healthy adolescent females ranging from lean to obese recruited for a healthy weight maintenance trial. Main Outcome Measure The relation between elevated “food addiction” scores and blood oxygen level-dependent fMRI activation in response to receipt and anticipated receipt of palatable food (chocolate milkshake). Results Food addiction scores (N = 39) correlated with greater activation in the anterior cingulate cortex (ACC), medial orbitofrontal cortex (OFC), and amygdala in response to anticipated receipt of food (P <0.05, false-discovery rate (FDR) corrected for multiple comparisons in small volumes). Participants with higher (n=15) versus lower (n=11) food addiction scores showed greater activation in the dorsolateral prefrontal cortex (DLPFC) and the caudate in response to anticipated receipt of food, but less activation in the lateral OFC in response to receipt of food (pFDR <0.05). Conclusions Similar patterns of neural activation are implicated in addictive-like eating behavior and substance dependence; elevated activation in reward circuitry in response to food cues and reduced activation of inhibitory regions in response to food intake. PMID:21464344

  14. ANT Advanced Neural Tool

    Energy Technology Data Exchange (ETDEWEB)

    Labrador, I.; Carrasco, R.; Martinez, L.

    1996-07-01

    This paper describes a practical introduction to the use of Artificial Neural Networks. Artificial Neural Nets are often used as an alternative to the traditional symbolic manipulation and first order logic used in Artificial Intelligence, due the high degree of difficulty to solve problems that can not be handled by programmers using algorithmic strategies. As a particular case of Neural Net a Multilayer Perception developed by programming in C language on OS9 real time operating system is presented. A detailed description about the program structure and practical use are included. Finally, several application examples that have been treated with the tool are presented, and some suggestions about hardware implementations. (Author) 15 refs.

  15. Neural correlates of viewing paintings

    DEFF Research Database (Denmark)

    Vartanian, Oshin; Skov, Martin

    2014-01-01

    Many studies involving functional magnetic resonance imaging (fMRI) have exposed participants to paintings under varying task demands. To isolate neural systems that are activated reliably across fMRI studies in response to viewing paintings regardless of variation in task demands, a quantitative...... meta-analysis of fifteen experiments using the activation likelihood estimation (ALE) method was conducted. As predicted, viewing paintings was correlated with activation in a distributed system including the occipital lobes, temporal lobe structures in the ventral stream involved in object (fusiform...... gyrus) and scene (parahippocampal gyrus) perception, and the anterior insula-a key structure in experience of emotion. In addition, we also observed activation in the posterior cingulate cortex bilaterally-part of the brain's default network. These results suggest that viewing paintings engages not only...

  16. Pax7 lineage contributions to the mammalian neural crest.

    Directory of Open Access Journals (Sweden)

    Barbara Murdoch

    Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

  17. Obesity is associated with high serotonin 4 receptor availability in the brain reward circuitry

    DEFF Research Database (Denmark)

    Haahr, M. E.; Rasmussen, Peter Mondrup; Madsen, K.

    2012-01-01

    The neurobiology underlying obesity is not fully understood. The neurotransmitter serotonin (5-HT) is established as a satiety-generating signal, but its rewarding role in feeding is less well elucidated. From animal experiments there is now evidence that the 5-HT4 receptor (5-HT4R) is involved...... between body mass index and the 5-HT4R density bilaterally in the two reward ‘hot spots’ nucleus accumbens and ventral pallidum, and additionally in the left hippocampal region and orbitofrontal cortex.These findings suggest that the 5-HT4R is critically involved in reward circuits that regulate people...

  18. Neural Systems Involved When Attending to a Speaker.

    Science.gov (United States)

    Kamourieh, Salwa; Braga, Rodrigo M; Leech, Robert; Newbould, Rexford D; Malhotra, Paresh; Wise, Richard J S

    2015-11-01

    Remembering what a speaker said depends on attention. During conversational speech, the emphasis is on working memory, but listening to a lecture encourages episodic memory encoding. With simultaneous interference from background speech, the need for auditory vigilance increases. We recreated these context-dependent demands on auditory attention in 2 ways. The first was to require participants to attend to one speaker in either the absence or presence of a distracting background speaker. The second was to alter the task demand, requiring either an immediate or delayed recall of the content of the attended speech. Across 2 fMRI studies, common activated regions associated with segregating attended from unattended speech were the right anterior insula and adjacent frontal operculum (aI/FOp), the left planum temporale, and the precuneus. In contrast, activity in a ventral right frontoparietal system was dependent on both the task demand and the presence of a competing speaker. Additional multivariate analyses identified other domain-general frontoparietal systems, where activity increased during attentive listening but was modulated little by the need for speech stream segregation in the presence of 2 speakers. These results make predictions about impairments in attentive listening in different communicative contexts following focal or diffuse brain pathology. © The Author 2015. Published by Oxford University Press.

  19. Effect of GABRA2 Genotype on Development of Incentive-Motivation Circuitry in a Sample Enriched for Alcoholism Risk

    Science.gov (United States)

    Heitzeg, Mary M; Villafuerte, Sandra; Weiland, Barbara J; Enoch, Mary-Anne; Burmeister, Margit; Zubieta, Jon-Kar; Zucker, Robert A

    2014-01-01

    Heightened reactivity of the incentive-motivation system has been proposed to underlie adolescent-typical risky behaviors, including problem alcohol involvement. However, even in adolescence considerable individual variation in these behaviors exists, which may have genetic underpinnings and be related to variations in risk for later alcohol use disorder (AUD). Variants in GABRA2 have been associated with adult alcohol dependence as well as phenotypic precursors, including impulsiveness and externalizing behaviors. We investigated the impact of GABRA2 on the developmental trajectory of nucleus accumbens (NAcc) activation during anticipation of monetary reward from childhood to young adulthood. Functional MRI during a monetary incentive delay task was collected in 175 participants, with the majority (n=151) undergoing repeated scanning at 1- to 2-year intervals. One group entered the study at age 8–13 years (n=76) and another entered at age 18–23 years (n=99). Most participants were children of alcoholics (79%) and thus at heightened risk for AUD. A total of 473 sessions were completed, covering ages 8–27 years. NAcc activation was heightened during adolescence compared with childhood and young adulthood. GABRA2 genotype (SNP rs279858) was associated with individual differences in NAcc activation specifically during adolescence, with the minor allele (G) associated with greater activation. Furthermore, NAcc activation mediated an effect of genotype on alcohol problems (n=104). This work demonstrates an impact of GABRA2 genotype on incentive-motivation neurocircuitry in adolescence, with implications for vulnerability to alcoholism. These findings represent an important step toward understanding the genetic and neural basis of individual differences in how risk for addiction unfolds across development. PMID:24975023

  20. Effect of GABRA2 genotype on development of incentive-motivation circuitry in a sample enriched for alcoholism risk.

    Science.gov (United States)

    Heitzeg, Mary M; Villafuerte, Sandra; Weiland, Barbara J; Enoch, Mary-Anne; Burmeister, Margit; Zubieta, Jon-Kar; Zucker, Robert A

    2014-12-01

    Heightened reactivity of the incentive-motivation system has been proposed to underlie adolescent-typical risky behaviors, including problem alcohol involvement. However, even in adolescence considerable individual variation in these behaviors exists, which may have genetic underpinnings and be related to variations in risk for later alcohol use disorder (AUD). Variants in GABRA2 have been associated with adult alcohol dependence as well as phenotypic precursors, including impulsiveness and externalizing behaviors. We investigated the impact of GABRA2 on the developmental trajectory of nucleus accumbens (NAcc) activation during anticipation of monetary reward from childhood to young adulthood. Functional MRI during a monetary incentive delay task was collected in 175 participants, with the majority (n = 151) undergoing repeated scanning at 1- to 2-year intervals. One group entered the study at age 8-13 years (n = 76) and another entered at age 18-23 years (n = 99). Most participants were children of alcoholics (79%) and thus at heightened risk for AUD. A total of 473 sessions were completed, covering ages 8-27 years. NAcc activation was heightened during adolescence compared with childhood and young adulthood. GABRA2 genotype (SNP rs279858) was associated with individual differences in NAcc activation specifically during adolescence, with the minor allele (G) associated with greater activation. Furthermore, NAcc activation mediated an effect of genotype on alcohol problems (n = 104). This work demonstrates an impact of GABRA2 genotype on incentive-motivation neurocircuitry in adolescence, with implications for vulnerability to alcoholism. These findings represent an important step toward understanding the genetic and neural basis of individual differences in how risk for addiction unfolds across development.

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

    Science.gov (United States)

    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.

  2. Hidden neural networks

    DEFF Research Database (Denmark)

    Krogh, Anders Stærmose; Riis, Søren Kamaric

    1999-01-01

    A general framework for hybrids of hidden Markov models (HMMs) and neural networks (NNs) called hidden neural networks (HNNs) is described. The article begins by reviewing standard HMMs and estimation by conditional maximum likelihood, which is used by the HNN. In the HNN, the usual HMM probability...... parameters are replaced by the outputs of state-specific neural networks. As opposed to many other hybrids, the HNN is normalized globally and therefore has a valid probabilistic interpretation. All parameters in the HNN are estimated simultaneously according to the discriminative conditional maximum...... likelihood criterion. The HNN can be viewed as an undirected probabilistic independence network (a graphical model), where the neural networks provide a compact representation of the clique functions. An evaluation of the HNN on the task of recognizing broad phoneme classes in the TIMIT database shows clear...

  3. [Neural codes for perception].

    Science.gov (United States)

    Romo, R; Salinas, E; Hernández, A; Zainos, A; Lemus, L; de Lafuente, V; Luna, R

    This article describes experiments designed to show the neural codes associated with the perception and processing of tactile information. The results of these experiments have shown the neural activity correlated with tactile perception. The neurones of the primary somatosensory cortex (S1) represent the physical attributes of tactile perception. We found that these representations correlated with tactile perception. By means of intracortical microstimulation we demonstrated the causal relationship between S1 activity and tactile perception. In the motor areas of the frontal lobe is to be found the connection between sensorial and motor representation whilst decisions are being taken. S1 generates neural representations of the somatosensory stimuli which seen to be sufficient for tactile perception. These neural representations are subsequently processed by central areas to S1 and seem useful in perception, memory and decision making.

  4. Neural Oscillators Programming Simplified

    Directory of Open Access Journals (Sweden)

    Patrick McDowell

    2012-01-01

    Full Text Available The neurological mechanism used for generating rhythmic patterns for functions such as swallowing, walking, and chewing has been modeled computationally by the neural oscillator. It has been widely studied by biologists to model various aspects of organisms and by computer scientists and robotics engineers as a method for controlling and coordinating the gaits of walking robots. Although there has been significant study in this area, it is difficult to find basic guidelines for programming neural oscillators. In this paper, the authors approach neural oscillators from a programmer’s point of view, providing background and examples for developing neural oscillators to generate rhythmic patterns that can be used in biological modeling and robotics applications.

  5. Folate receptors and neural tube closure.

    Science.gov (United States)

    Saitsu, Hirotomo

    2017-09-01

    Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5-8.0/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse Folr1 (formerly referred to as Fbp1) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of Folr1 in developing mouse embryos, showing a close association between Folr1 and anterior neural tube closure. Transient transgenic analysis was performed using lacZ as a reporter; we identified a 1.1-kb enhancer that directs lacZ expression in the neural tube and optic vesicle in a manner that is similar to endogenous Folr1. The 1.1-kb enhancer sequences were highly conserved between humans and mice, suggesting that human FOLR1 is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD. © 2017 Japanese Teratology Society.

  6. Neural substrates of decision-making.

    Science.gov (United States)

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

    2016-06-01

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

  7. Neural cryptography with feedback.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  8. Neural cryptography with feedback

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  9. Neural network applications

    Science.gov (United States)

    Padgett, Mary L.; Desai, Utpal; Roppel, T.A.; White, Charles R.

    1993-01-01

    A design procedure is suggested for neural networks which accommodates the inclusion of such knowledge-based systems techniques as fuzzy logic and pairwise comparisons. The use of these procedures in the design of applications combines qualitative and quantitative factors with empirical data to yield a model with justifiable design and parameter selection procedures. The procedure is especially relevant to areas of back-propagation neural network design which are highly responsive to the use of precisely recorded expert knowledge.

  10. Building Neural Net Software

    OpenAIRE

    Neto, João Pedro; Costa, José Félix

    1999-01-01

    In a recent paper [Neto et al. 97] we showed that programming languages can be translated on recurrent (analog, rational weighted) neural nets. The goal was not efficiency but simplicity. Indeed we used a number-theoretic approach to machine programming, where (integer) numbers were coded in a unary fashion, introducing a exponential slow down in the computations, with respect to a two-symbol tape Turing machine. Implementation of programming languages in neural nets turns to be not only theo...

  11. NEMEFO: NEural MEteorological FOrecast

    Energy Technology Data Exchange (ETDEWEB)

    Pasero, E.; Moniaci, W.; Meindl, T.; Montuori, A. [Polytechnic of Turin (Italy). Dept. of Electronics

    2004-07-01

    Artificial Neural Systems are a well-known technique used to classify and recognize objects. Introducing the time dimension they can be used to forecast numerical series. NEMEFO is a ''nowcasting'' tool, which uses both statistical and neural systems to forecast meteorological data in a restricted area close to a meteorological weather station in a short time range (3 hours). Ice, fog, rain are typical events which can be anticipated by NEMEFO. (orig.)

  12. Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain.

    Science.gov (United States)

    Hulbert, Samuel W; Jiang, Yong-Hui

    2017-04-01

    Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders. Recently, researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time. Thus, a clearer picture is starting to emerge of the cell types, circuits, brain regions, and developmental time periods underlying ASDs. ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons, different neurotransmitter systems, and cells specific to the forebrain or cerebellum. In addition, mutations have been induced or corrected in adult mice, providing some evidence for the plasticity and reversibility of core ASD symptoms. The limited availability of Cre lines that are highly specific to certain cell types or time periods provides a challenge to determining the cellular and circuitry bases of autism, but other technological advances may eventually overcome this obstacle.

  13. In search of the next memory inside the circuitry from the oldest to the emerging non-volatile memories

    CERN Document Server

    Campardo, Giovanni

    2017-01-01

    This book provides students and practicing chip designers with an easy-to-follow yet thorough, introductory treatment of the most promising emerging memories under development in the industry. Focusing on the chip designer rather than the end user, this book offers expanded, up-to-date coverage of emerging memories circuit design. After an introduction on the old solid-state memories and the fundamental limitations soon to be encountered, the working principle and main technology issues of each of the considered technologies (PCRAM, MRAM, FeRAM, ReRAM) are reviewed and a range of topics related to design is explored: the array organization, sensing and writing circuitry, programming algorithms and error correction techniques are reviewed comparing the approach followed and the constraints for each of the technologies considered. Finally the issue of radiation effects on memory devices has been briefly treated. Additionally some considerations are entertained about how emerging memories can find a place in the...

  14. Influence of alcohol use and family history of alcoholism on neural response to alcohol cues in college drinkers.

    Science.gov (United States)

    Dager, Alecia D; Anderson, Beth M; Stevens, Michael C; Pulido, Carmen; Rosen, Rivkah; Jiantonio-Kelly, Rachel E; Sisante, Jason-Flor; Raskin, Sarah A; Tennen, Howard; Austad, Carol S; Wood, Rebecca M; Fallahi, Carolyn R; Pearlson, Godfrey D

    2013-01-01

    personal drinking. Heavy drinking and family history of alcoholism may have differential impacts on neural circuitry involved in cue reactivity. Copyright © 2012 by the Research Society on Alcoholism.

  15. The neural basis of unwanted thoughts during resting state.

    Science.gov (United States)

    Kühn, Simone; Vanderhasselt, Marie-Anne; De Raedt, Rudi; Gallinat, Jürgen

    2014-09-01

    Human beings are constantly engaged in thought. Sometimes thoughts occur repetitively and can become distressing. Up to now the neural bases of these intrusive or unwanted thoughts is largely unexplored. To study the neural correlates of unwanted thoughts, we acquired resting-state fMRI data of 41 female healthy subjects and assessed the self-reported amount of unwanted thoughts during measurement. We analyzed local connectivity by means of regional homogeneity (ReHo) and functional connectivity of a seed region. More unwanted thoughts (state) were associated with lower ReHo in right dorsolateral prefrontal cortex (DLPFC) and higher ReHo in left striatum (putamen). Additional seed-based analysis revealed higher functional connectivity of the left striatum with left inferior frontal gyrus (IFG) in participants reporting more unwanted thoughts. The state-dependent higher connectivty in left striatum was positively correlated with rumination assessed with a dedicated questionnaire focussing on trait aspects. Unwanted thoughts are associated with activity in the fronto-striatal brain circuitry. The reduction of local connectivity in DLPFC could reflect deficiencies in thought suppression processes, whereas the hightened activity in left striatum could imply an imbalance of gating mechanisms housed in basal ganglia. Its functional connectivity to left IFG is discussed as the result of thought-related speech processes. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Nonlinear modeling of neural population dynamics for hippocampal prostheses.

    Science.gov (United States)

    Song, Dong; Chan, Rosa H M; Marmarelis, Vasilis Z; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W

    2009-11-01

    Developing a neural prosthesis for the damaged hippocampus requires restoring the transformation of population neural activities performed by the hippocampal circuitry. To bypass a damaged region, output spike trains need to be predicted from the input spike trains and then reinstated through stimulation. We formulate a multiple-input, multiple-output (MIMO) nonlinear dynamic model for the input-output transformation of spike trains. In this approach, a MIMO model comprises a series of physiologically-plausible multiple-input, single-output (MISO) neuron models that consist of five components each: (1) feedforward Volterra kernels transforming the input spike trains into the synaptic potential, (2) a feedback kernel transforming the output spikes into the spike-triggered after-potential, (3) a noise term capturing the system uncertainty, (4) an adder generating the pre-threshold potential, and (5) a threshold function generating output spikes. It is shown that this model is equivalent to a generalized linear model with a probit link function. To reduce model complexity and avoid overfitting, statistical model selection and cross-validation methods are employed to choose the significant inputs and interactions between inputs. The model is applied successfully to the hippocampal CA3-CA1 population dynamics. Such a model can serve as a computational basis for the development of hippocampal prostheses.

  17. Neural and neurochemical basis of reinforcement-guided decision making.

    Science.gov (United States)

    Khani, Abbas; Rainer, Gregor

    2016-08-01

    Decision making is an adaptive behavior that takes into account several internal and external input variables and leads to the choice of a course of action over other available and often competing alternatives. While it has been studied in diverse fields ranging from mathematics, economics, ecology, and ethology to psychology and neuroscience, recent cross talk among perspectives from different fields has yielded novel descriptions of decision processes. Reinforcement-guided decision making models are based on economic and reinforcement learning theories, and their focus is on the maximization of acquired benefit over a defined period of time. Studies based on reinforcement-guided decision making have implicated a large network of neural circuits across the brain. This network includes a wide range of cortical (e.g., orbitofrontal cortex and anterior cingulate cortex) and subcortical (e.g., nucleus accumbens and subthalamic nucleus) brain areas and uses several neurotransmitter systems (e.g., dopaminergic and serotonergic systems) to communicate and process decision-related information. This review discusses distinct as well as overlapping contributions of these networks and neurotransmitter systems to the processing of decision making. We end the review by touching on neural circuitry and neuromodulatory regulation of exploratory decision making. Copyright © 2016 the American Physiological Society.

  18. TUTORIAL: The dynamic neural field approach to cognitive robotics

    Science.gov (United States)

    Erlhagen, Wolfram; Bicho, Estela

    2006-09-01

    This tutorial presents an architecture for autonomous robots to generate behavior in joint action tasks. To efficiently interact with another agent in solving a mutual task, a robot should be endowed with cognitive skills such as memory, decision making, action understanding and prediction. The proposed architecture is strongly inspired by our current understanding of the processing principles and the neuronal circuitry underlying these functionalities in the primate brain. As a mathematical framework, we use a coupled system of dynamic neural fields, each representing the basic functionality of neuronal populations in different brain areas. It implements goal-directed behavior in joint action as a continuous process that builds on the interpretation of observed movements in terms of the partner's action goal. We validate the architecture in two experimental paradigms: (1) a joint search task; (2) a reproduction of an observed or inferred end state of a grasping-placing sequence. We also review some of the mathematical results about dynamic neural fields that are important for the implementation work. .

  19. TPX2-p53-GLIPR1 regulatory circuitry in cell proliferation, invasion, and tumor growth of bladder cancer.

    Science.gov (United States)

    Yan, Liang; Li, Qi; Yang, Juan; Qiao, Baoping

    2017-08-11

    The targeting protein for Xenopus kinesin-like protein 2 (TPX2) is associated with the metastasis and prognosis of bladder cancer. p53 is closely related to the progression of bladder cancer. Human glioma pathogenesis-related protein 1 (GLIPR1) is a p53 target gene with antitumor activity. This study aims to explore the interplay between TPX2, p53, and GLIPR1 and its correlation with cell proliferation, invasion, and tumor growth in bladder cancer. Here, Western blot and qRT-PCR analysis revealed that TPX2 at both mRNA and protein levels was up-regulated in bladder carcinoma tissues compared to their paired adjacent normal tissues. Additionally, tissues expressing high TPX2 level exhibited high p53 level and low GLIPR1 level. The expressions of TPX2 and p53 in non-muscle-invasive bladder cancer cells (KK47 and RT4) were lower than those in muscle-invasive bladder cancer cells (T24, 5637, and UM-UC-3), while GLIPR1 showed the converse expression pattern. Further investigation revealed that TPX2 activated the synthesis of p53; and GLIPR1 is up-regulated by wild-type (wt)-p53 but not affected by mutated p53; Additionally, GLIPR1 inhibited TPX2. These data suggested a TPX2-p53-GLIPR1 regulatory circuitry. Meanwhile, TPX2 overexpression promoted while overexpression of GLIPR1 or p53 inhibited bladder cancer growth. Interestingly, in T24 cells with mutated p53, p53 silence suppressed bladder cancer growth. This study identified a novel TPX2-p53-GLIPR1 regulatory circuitry which modulated cell proliferation, migration, invasion, and tumorigenicity of bladder cancer. Our findings provide new insight into underlying mechanisms of tumorigenesis and novel therapeutic options in bladder cancer. © 2017 Wiley Periodicals, Inc.

  20. Neural correlates of motor learning, transfer of learning, and learning to learn.

    Science.gov (United States)

    Seidler, Rachael D

    2010-01-01

    Recent studies on the neural bases of sensorimotor adaptation demonstrate that the cerebellar and striatal thalamocortical pathways contribute to early learning. Transfer of learning involves a reduction in the contribution of early learning networks and increased reliance on the cerebellum. The neural correlates of learning to learn remain to be determined but likely involve enhanced functioning of the general aspects of early learning.

  1. Artificial astrocytes improve neural network performance.

    Science.gov (United States)

    Porto-Pazos, Ana B; Veiguela, Noha; Mesejo, Pablo; Navarrete, Marta; Alvarellos, Alberto; Ibáñez, Oscar; Pazos, Alejandro; Araque, Alfonso

    2011-04-19

    Compelling evidence indicates the existence of bidirectional communication between astrocytes and neurons. Astrocytes, a type of glial cells classically considered to be passive supportive cells, have been recently demonstrated to be actively involved in the processing and regulation of synaptic information, suggesting that brain function arises from the activity of neuron-glia networks. However, the actual impact of astrocytes in neural network function is largely unknown and its application in artificial intelligence remains untested. We have investigated the consequences of including artificial astrocytes, which present the biologically defined properties involved in astrocyte-neuron communication, on artificial neural network performance. Using connectionist systems and evolutionary algorithms, we have compared the performance of artificial neural networks (NN) and artificial neuron-glia networks (NGN) to solve classification problems. We show that the degree of success of NGN is superior to NN. Analysis of performances of NN with different number of neurons or different architectures indicate that the effects of NGN cannot be accounted for an increased number of network elements, but rather they are specifically due to astrocytes. Furthermore, the relative efficacy of NGN vs. NN increases as the complexity of the network increases. These results indicate that artificial astrocytes improve neural network performance, and established the concept of Artificial Neuron-Glia Networks, which represents a novel concept in Artificial Intelligence with implications in computational science as well as in the understanding of brain function.

  2. Neural mechanisms supporting the extraction of general knowledge across episodic memories

    NARCIS (Netherlands)

    Sweegers, C.C.; Takashima, A.; Fernandez, G.S.E.; Talamini, L.M.

    2014-01-01

    General knowledge acquisition entails the extraction of statistical regularities from the environment. At high levels of complexity, this may involve the extraction, and consolidation, of associative regularities across event memories. The underlying neural mechanisms would likely involve a

  3. The neural basis of theory of mind and its relationship to social functioning and social anhedonia in individuals with schizophrenia

    Directory of Open Access Journals (Sweden)

    David Dodell-Feder

    2014-01-01

    Full Text Available Theory of mind (ToM, the ability to attribute and reason about the mental states of others, is a strong determinant of social functioning among individuals with schizophrenia. Identifying the neural bases of ToM and their relationship to social functioning may elucidate functionally relevant neurobiological targets for intervention. ToM ability may additionally account for other social phenomena that affect social functioning, such as social anhedonia (SocAnh. Given recent research in schizophrenia demonstrating improved neural functioning in response to increased use of cognitive skills, it is possible that SocAnh, which decreases one's opportunity to engage in ToM, could compromise social functioning through its deleterious effect on ToM-related neural circuitry. Here, twenty individuals with schizophrenia and 18 healthy controls underwent fMRI while performing the False-Belief Task. Aspects of social functioning were assessed using multiple methods including self-report (Interpersonal Reactivity Index, Social Adjustment Scale, clinician-ratings (Global Functioning Social Scale, and performance-based tasks (MSCEIT—Managing Emotions. SocAnh was measured with the Revised Social Anhedonia Scale. Region-of-interest and whole-brain analyses revealed reduced recruitment of medial prefrontal cortex (MPFC for ToM in individuals with schizophrenia. Across all participants, activity in this region correlated with most social variables. Mediation analysis revealed that neural activity for ToM in MPFC accounted for the relationship between SocAnh and social functioning. These findings demonstrate that reduced recruitment of MPFC for ToM is an important neurobiological determinant of social functioning. Furthermore, SocAhn may affect social functioning through its impact on ToM-related neural circuitry. Together, these findings suggest ToM ability as an important locus for intervention.

  4. Risperidone and Divalproex Differentially Engage the Fronto-Striato-Temporal Circuitry in Pediatric Mania: A Pharmacological Functional Magnetic Resonance Imaging Study

    Science.gov (United States)

    Pavuluri, Mani N.; Passarotti, Alessandra M.; Fitzgerald, Jacklynn M.; Wegbreit, Ezra; Sweeney, John A.

    2012-01-01

    Objective: The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD). Method: This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 [plus or minus] 2.5…

  5. Neural network modeling of emotion

    Science.gov (United States)

    Levine, Daniel S.

    2007-03-01

    This article reviews the history and development of computational neural network modeling of cognitive and behavioral processes that involve emotion. The exposition starts with models of classical conditioning dating from the early 1970s. Then it proceeds toward models of interactions between emotion and attention. Then models of emotional influences on decision making are reviewed, including some speculative (not and not yet simulated) models of the evolution of decision rules. Through the late 1980s, the neural networks developed to model emotional processes were mainly embodiments of significant functional principles motivated by psychological data. In the last two decades, network models of these processes have become much more detailed in their incorporation of known physiological properties of specific brain regions, while preserving many of the psychological principles from the earlier models. Most network models of emotional processes so far have dealt with positive and negative emotion in general, rather than specific emotions such as fear, joy, sadness, and anger. But a later section of this article reviews a few models relevant to specific emotions: one family of models of auditory fear conditioning in rats, and one model of induced pleasure enhancing creativity in humans. Then models of emotional disorders are reviewed. The article concludes with philosophical statements about the essential contributions of emotion to intelligent behavior and the importance of quantitative theories and models to the interdisciplinary enterprise of understanding the interactions of emotion, cognition, and behavior.

  6. The neural subjective frame: from bodily signals to perceptual consciousness

    Science.gov (United States)

    Park, Hyeong-Dong; Tallon-Baudry, Catherine

    2014-01-01

    The report ‘I saw the stimulus’ operationally defines visual consciousness, but where does the ‘I’ come from? To account for the subjective dimension of perceptual experience, we introduce the concept of the neural subjective frame. The neural subjective frame would be based on the constantly updated neural maps of the internal state of the body and constitute a neural referential from which first person experience can be created. We propose to root the neural subjective frame in the neural representation of visceral information which is transmitted through multiple anatomical pathways to a number of target sites, including posterior insula, ventral anterior cingulate cortex, amygdala and somatosensory cortex. We review existing experimental evidence showing that the processing of external stimuli can interact with visceral function. The neural subjective frame is a low-level building block of subjective experience which is not explicitly experienced by itself which is necessary but not sufficient for perceptual experience. It could also underlie other types of subjective experiences such as self-consciousness and emotional feelings. Because the neural subjective frame is tightly linked to homeostatic regulations involved in vigilance, it could also make a link between state and content consciousness. PMID:24639580

  7. Conducting Polymers for Neural Prosthetic and Neural Interface Applications

    Science.gov (United States)

    2015-01-01

    Neural interfacing devices are an artificial mechanism for restoring or supplementing the function of the nervous system lost as a result of injury or disease. Conducting polymers (CPs) are gaining significant attention due to their capacity to meet the performance criteria of a number of neuronal therapies including recording and stimulating neural activity, the regeneration of neural tissue and the delivery of bioactive molecules for mediating device-tissue interactions. CPs form a flexible platform technology that enables the development of tailored materials for a range of neuronal diagnostic and treatment therapies. In this review the application of CPs for neural prostheses and other neural interfacing devices are discussed, with a specific focus on neural recording, neural stimulation, neural regeneration, and therapeutic drug delivery. PMID:26414302

  8. Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours.

    Science.gov (United States)

    Voon, Valerie; Mole, Thomas B; Banca, Paula; Porter, Laura; Morris, Laurel; Mitchell, Simon; Lapa, Tatyana R; Karr, Judy; Harrison, Neil A; Potenza, Marc N; Irvine, Michael

    2014-01-01

    Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions.

  9. Young adult smokers' neural response to graphic cigarette warning labels

    Directory of Open Access Journals (Sweden)

    Adam E. Green

    2016-06-01

    Conclusions: In this sample of young adult smokers, GWLs promoted neural activation in brain regions involved in cognitive and affective decision-making and memory formation and the effects of GWLs did not differ on branded or plain cigarette packaging. These findings complement other recent neuroimaging GWL studies conducted with older adult smokers and with adolescents by demonstrating similar patterns of neural activation in response to GWLs among young adult smokers.

  10. Hyperbolic Hopfield neural networks.

    Science.gov (United States)

    Kobayashi, M

    2013-02-01

    In recent years, several neural networks using Clifford algebra have been studied. Clifford algebra is also called geometric algebra. Complex-valued Hopfield neural networks (CHNNs) are the most popular neural networks using Clifford algebra. The aim of this brief is to construct hyperbolic HNNs (HHNNs) as an analog of CHNNs. Hyperbolic algebra is a Clifford algebra based on Lorentzian geometry. In this brief, a hyperbolic neuron is defined in a manner analogous to a phasor neuron, which is a typical complex-valued neuron model. HHNNs share common concepts with CHNNs, such as the angle and energy. However, HHNNs and CHNNs are different in several aspects. The states of hyperbolic neurons do not form a circle, and, therefore, the start and end states are not identical. In the quantized version, unlike complex-valued neurons, hyperbolic neurons have an infinite number of states.

  11. Neural Semantic Encoders.

    Science.gov (United States)

    Munkhdalai, Tsendsuren; Yu, Hong

    2017-04-01

    We present a memory augmented neural network for natural language understanding: Neural Semantic Encoders. NSE is equipped with a novel memory update rule and has a variable sized encoding memory that evolves over time and maintains the understanding of input sequences through read, compose and write operations. NSE can also access multiple and shared memories. In this paper, we demonstrated the effectiveness and the flexibility of NSE on five different natural language tasks: natural language inference, question answering, sentence classification, document sentiment analysis and machine translation where NSE achieved state-of-the-art performance when evaluated on publically available benchmarks. For example, our shared-memory model showed an encouraging result on neural machine translation, improving an attention-based baseline by approximately 1.0 BLEU.

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

    Science.gov (United States)

    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

  13. Psychological and neural mechanisms of experimental extinction: a selective review.

    Science.gov (United States)

    Delamater, Andrew R; Westbrook, R Frederick

    2014-02-01

    The present review examines key psychological concepts in the study of experimental extinction and implications these have for an understanding of the underlying neurobiology of extinction learning. We suggest that many of the signature characteristics of extinction learning (spontaneous recovery, renewal, reinstatement, rapid reacquisition) can be accommodated by the standard associative learning theory assumption that extinction results in partial erasure of the original learning together with new inhibitory learning. Moreover, we consider recent behavioral and neural evidence that supports the partial erasure view of extinction, but also note shortcomings in our understanding of extinction circuits as these relate to the negative prediction error concept. Recent work suggests that common prediction error and stimulus-specific prediction error terms both may be required to explain neural plasticity both in acquisition and extinction learning. In addition, we suggest that many issues in the content of extinction learning have not been fully addressed in current research, but that neurobiological approaches should be especially helpful in addressing such issues. These include questions about the nature of extinction learning (excitatory CS-No US, inhibitory CS-US learning, occasion setting processes), especially as this relates to studies of the micro-circuitry of extinction, as well as its representational content (sensory, motivational, response). An additional understudied problem in extinction research is the role played by attention processes and their underlying neural networks, although some research and theory converge on the idea that extinction is accompanied by attention decrements (i.e., habituation-like processes). Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Neural correlates of human wayfinding in stroke patients.

    NARCIS (Netherlands)

    Asselen, M. van; Kessels, R.P.C.; Kappelle, L.J.; Neggers, S.F.W.; Frijns, C.J.M.; Postma, A.

    2006-01-01

    Wayfinding is a complex cognitive function involving different types of information, such as knowledge about landmarks and direction information. This variety of processes suggest that multiple neural mechanisms are involved, e.g., the hippocampal system, the posterior parietal and temporal cortical

  15. Neural networks of human nature and nurture

    Directory of Open Access Journals (Sweden)

    Daniel S. Levine

    2009-11-01

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

  16. A neural basis for general intelligence

    OpenAIRE

    Duncan, J.; Seitz, R.J.; Kolodny, J.; Bor, D.; Herzog, H; Ahmed, A.; Newell, F. N.; Emslie, H

    2000-01-01

    Universal positive correlations between different cognitive tests motivate the concept of "general intelligence" or Spearman's g. Here the neural basis for g is investigated by means of positron emission tomography. Spatial, verbal, and perceptuo-motor tasks with high-g involvement are compared with matched Low-g control tasks. In contrast to the common view that g reflects a broad sample of major cognitive functions, high-g tasks do not show diffuse recruitment of multiple brain regions. Ins...

  17. Introduction to Artificial Neural Networks

    DEFF Research Database (Denmark)

    Larsen, Jan

    1999-01-01

    The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks.......The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks....

  18. Deconvolution using a neural network

    Energy Technology Data Exchange (ETDEWEB)

    Lehman, S.K.

    1990-11-15

    Viewing one dimensional deconvolution as a matrix inversion problem, we compare a neural network backpropagation matrix inverse with LMS, and pseudo-inverse. This is a largely an exercise in understanding how our neural network code works. 1 ref.

  19. Dopamine and extinction: A convergence of theory with fear and reward circuitry

    Science.gov (United States)

    Abraham, Antony D.; Neve, Kim A.; Lattal, K. Matthew

    2014-01-01

    Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine’s function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes. PMID:24269353

  20. Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia.

    Directory of Open Access Journals (Sweden)

    Martina Krenzer

    Full Text Available Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM sleep.To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2 or vesicular GABA-glycine transporter (VGAT genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG and lateral pontine tegmentum (LPT are not critically involved in REM sleep control.These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD.

  1. Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity.

    Science.gov (United States)

    Bazan, Nicolas G; Musto, Alberto E; Knott, Eric J

    2011-10-01

    , pharmaceutical intervention, and clinical translation involving DHA-mediated signaling.

  2. Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: interaction with postnatal nutritional environment.

    Directory of Open Access Journals (Sweden)

    Hui Chen

    Full Text Available OBJECTIVE: Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY and suppressor proopiomelanocortin (POMC in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD consumption are unclear. RESEARCH DESIGN AND METHODS: Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control. At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid metabolic markers were measured. RESULTS: Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain. CONCLUSIONS: Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via different neuroendocrine mechanism. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring.

  3. Balancing the excitability of M1 circuitry during movement observation without overt replication

    Directory of Open Access Journals (Sweden)

    Pablo eArias

    2014-09-01

    Full Text Available Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE, and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: i electric cervicomedullary stimulation, to test spinal excitability, ii paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition SICI and intracortical facilitation ICF and iii continuous theta-burst stimulation (cTBS, to modulate the excitability of M1cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.

  4. Neural systems for tactual memories.

    Science.gov (United States)

    Bonda, E; Petrides, M; Evans, A

    1996-04-01

    1. The aim of this study was to investigate the neural systems involved in the memory processing of experiences through touch. 2. Regional cerebral blood flow was measured with positron emission tomography by means of the water bolus H2(15)O methodology in human subjects as they performed tasks involving different levels of tactual memory. In one of the experimental tasks, the subjects had to palpate nonsense shapes to match each one to a previously learned set, thus requiring constant reference to long-term memory. The other experimental task involved judgements of the recent recurrence of shapes during the scanning period. A set of three control tasks was used to control for the type of exploratory movements and sensory processing inherent in the two experimental tasks. 3. Comparisons of the distribution of activity between the experimental and the control tasks were carried out by means of the subtraction method. In relation to the control conditions, the two experimental tasks requiring memory resulted in significant changes within the posteroventral insula and the central opercular region. In addition, the task requiring recall from long-term memory yielded changes in the perirhinal cortex. 4. The above findings demonstrated that a ventrally directed parietoinsular pathway, leading to the posteroventral insula and the perirhinal cortex, constitutes a system by which long-lasting representations of tactual experiences are formed. It is proposed that the posteroventral insula is involved in tactual feature analysis, by analogy with the similar role of the inferotemporal cortex in vision, whereas the perirhinal cortex is further involved in the integration of these features into long-lasting representations of somatosensory experiences.

  5. Neural Network Ensembles

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Salamon, Peter

    1990-01-01

    We propose several means for improving the performance an training of neural networks for classification. We use crossvalidation as a tool for optimizing network parameters and architecture. We show further that the remaining generalization error can be reduced by invoking ensembles of similar...... networks....

  6. Neural systems for control

    National Research Council Canada - National Science Library

    Omidvar, Omid; Elliott, David L

    1997-01-01

    ... is reprinted with permission from A. Barto, "Reinforcement Learning," Handbook of Brain Theory and Neural Networks, M.A. Arbib, ed.. The MIT Press, Cambridge, MA, pp. 804-809, 1995. Chapter 4, Figures 4-5 and 7-9 and Tables 2-5, are reprinted with permission, from S. Cho, "Map Formation in Proprioceptive Cortex," International Jour...

  7. Neural Tube Defects

    Science.gov (United States)

    ... pregnancies each year in the United States. A baby’s neural tube normally develops into the brain and spinal cord. ... fluid in the brain. This is called hydrocephalus. Babies with this condition are treated with surgery to insert a tube (called a shunt) into the brain. The shunt ...

  8. CHD7 cooperates with PBAF to control multipotent neural crest formation

    Science.gov (United States)

    Bajpai, Ruchi; Chen, Denise A.; Rada-Iglesias, Alvaro; Zhang, Junmei; Xiong, Yiqin; Helms, Jill; Chang, Ching-Pin; Zhao, Yingming; Swigut, Tomek; Wysocka, Joanna

    2010-01-01

    Summary Heterozygous mutations in the gene encoding CHD7, an ATP-dependent chromatin remodeler result in a complex constellation of congenital anomalies called CHARGE syndrome. Here we show that in humans and in Xenopus, CHD7 is essential for the formation of multipotent migratory neural crest cells, a transient cell population that is ectodermal in origin, but undergoes a major gene expression reprogramming to acquire a remarkably broad differentiation potential and ability to migrate throughout the body to give rise to bones, cartilages, nerves, and cardiac structures. We demonstrate that CHD7 function is essential for activation of core components of neural crest transcriptional circuitry, including Sox9, Twist and Slug. Moreover, the major features of CHARGE are recapitulated in Xenopus embryo by the downregulation of CHD7 levels or overexpression of its catalytically inactive ATP-ase mutant. We further show that in human multipotent neural crest cells, CHD7 associates with a BRG1-containing complex PBAF, and both factors co-occupy a neural crest-specific distal SOX9 enhancer, as well as a novel genomic element located upstream from TWIST1 gene and marked by H3K4me1. Furthermore, in the embryo CHD7 and PBAF act synergistically to promote neural crest gene expression and cell migration. Our work identifies an evolutionary conserved role for CHD7 in orchestrating neural crest gene expression programs, provides insights into the synergistic regulation of distal genomic elements by two distinct chromatin remodelers, and illuminates the patho-embryology of CHARGE syndrome. PMID:20130577

  9. Epigenomic Landscapes of hESC-Derived Neural Rosettes: Modeling Neural Tube Formation and Diseases.

    Science.gov (United States)

    Valensisi, Cristina; Andrus, Colin; Buckberry, Sam; Doni Jayavelu, Naresh; Lund, Riikka J; Lister, Ryan; Hawkins, R David

    2017-08-08

    We currently lack a comprehensive understanding of the mechanisms underlying neural tube formation and their contributions to neural tube defects (NTDs). Developing a model to study such a complex morphogenetic process, especially one that models human-specific aspects, is critical. Three-dimensional, human embryonic stem cell (hESC)-derived neural rosettes (NRs) provide a powerful resource for in vitro modeling of human neural tube formation. Epigenomic maps reveal enhancer elements unique to NRs relative to 2D systems. A master regulatory network illustrates that key NR properties are related to their epigenomic landscapes. We found that folate-associated DNA methylation changes were enriched within NR regulatory elements near genes involved in neural tube formation and metabolism. Our comprehensive regulatory maps offer insights into the mechanisms by which folate may prevent NTDs. Lastly, our distal regulatory maps provide a better understanding of the potential role of neurological-disorder-associated SNPs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. A low-cost dielectric spectroscopic system using metamaterial open horn-ring resonator-inspired BSF and detection circuitry

    Science.gov (United States)

    Kumari, Ratnesh; Patel, Piyush N.

    2016-07-01

    The sensitivity in a lower microwave band dielectric spectroscopic system is relatively less compared to that of millimeter wave and terahertz system. This work reports modeling and development of an epsilon-negative metamaterial resonator-inspired microwave band-stop filter as a prototype device and its detection circuitry for the spectroscopic analysis of dielectric samples in S-band. The device structure consists of a diamond-shaped patch with a complementary open split horn-ring resonator, fabricated on a Neltech substrate of relative permittivity ( ɛ r = 3.2). The measured transmission coefficient at 2.2 GHz and simulated result at 2.24 GHz demonstrate an excellent accuracy in the device fabrication. A low-cost connector-type microwave signal detection system was assembled for the real-time transduction of device signal into an equivalent DC voltage. Further, a single channel cavity developed using polydimethylsiloxane was placed over the resonator gap for analyzing the perturbation effect of electric field intensity on the resonance and circuit output DC level for different dielectric samples under test. The performed calibrations show linearity up to 82.5 % in the device response.

  11. Broadband wireless radio frequency power telemetry using a metamaterial resonator embedded with non-foster impedance circuitry

    Science.gov (United States)

    Fu, Guoqing; Sonkusale, Sameer

    2015-05-01

    Wireless powering of implantable biomedical devices and smart radio frequency identification (RFID) tags with very low profile antennas is desired. We propose a low profile electrically small antenna for near-field wireless power telemetry employing a metamaterial Split Ring Resonator (SRR) antenna. SRRs can be designed for operation over wide frequencies from RF to visible. However, they are inherently narrowband making them sensitive to component mismatch with respect to external transmit antenna. Here, we propose an embedding of a non-foster impedance circuitry into the metamaterial SRR structure that imparts conjugate negative complex impedance to this resonator antenna thereby increasing the effective bandwidth and thus overcoming the fundamental limit for efficient signal coupling. We demonstrate the concept through extensive numerical simulations and a prototype system at the board level using discrete off-the-shelf components and printed circuit SRR antenna at 500 MHz. We show that the power transfer between SRR receive antenna and the external transmit loop antenna is improved by more than 8 dB over a wide frequency band (from 525 MHz to 635 MHz), before and after non-foster circuit activation.

  12. A digitally controlled AGC loop circuitry for GNSS receiver chip with a binary weighted accurate dB-linear PGA

    Science.gov (United States)

    Gang, Jin; Yiqi, Zhuang; Yue, Yin; Miao, Cui

    2015-03-01

    A novel digitally controlled automatic gain control (AGC) loop circuitry for the global navigation satellite system (GNSS) receiver chip is presented. The entire AGC loop contains a programmable gain amplifier (PGA), an AGC circuit and an analog-to-digital converter (ADC), which is implemented in a 0.18 μm complementary metal-oxide-semiconductor (CMOS) process and measured. A binary-weighted approach is proposed in the PGA to achieve wide dB-linear gain control with small gain error. With binary-weighted cascaded amplifiers for coarse gain control, and parallel binary-weighted trans-conductance amplifier array for fine gain control, the PGA can provide a 64 dB dynamic range from -4 to 60 dB in 1.14 dB gain steps with a less than 0.15 dB gain error. Based on the Gaussian noise statistic characteristic of the GNSS signal, a digital AGC circuit is also proposed with low area and fast settling. The feed-backward AGC loop occupies an area of 0.27 mm2 and settles within less than 165 μs while consuming an average current of 1.92 mA at 1.8 V.

  13. Netrin-1-dependent spinal interneuron subtypes are required for the formation of left-right alternating locomotor circuitry.

    Science.gov (United States)

    Rabe, Nadine; Gezelius, Henrik; Vallstedt, Anna; Memic, Fatima; Kullander, Klas

    2009-12-16

    Neuronal circuits in the spinal cord that produce the rhythmic and coordinated activities necessary for limb movements are referred to as locomotor central pattern generators (CPGs). The identities and preceding development of neurons essential for coordination between left and right limbs are not yet known. We show that the ventral floor plate chemoattractant Netrin-1 preferentially guides dorsally originating subtypes of commissural interneurons, the majority of which are inhibitory. In contrast, the excitatory and ventralmost V3 subtype of interneurons have a normal number of commissural fibers in Netrin-1 mutant mice, thus being entirely independent of Netrin-1-mediated attraction. This selective loss of commissural fibers in Netrin-1 mutant m