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Sample records for neural reward circuits

  1. Acute Stress Influences Neural Circuits of Reward Processing

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    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.

  2. Neural bases of food-seeking: affect, arousal and reward in corticostriatolimbic circuits.

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    Balleine, Bernard W

    2005-12-15

    Recent studies suggest that there are multiple 'reward' or 'reward-like' systems that control food seeking; evidence points to two distinct learning processes and four modulatory processes that contribute to the performance of food-related instrumental actions. The learning processes subserve the acquisition of goal-directed and habitual actions and involve the dorsomedial and dorsolateral striatum, respectively. Access to food can function both to reinforce habits and as a reward or goal for actions. Encoding and retrieving the value of a goal appears to be mediated by distinct processes that, contrary to the somatic marker hypothesis, do not appear to depend on a common mechanism but on emotional and more abstract evaluative processes, respectively. The anticipation of reward on the basis of environmental events exerts a further modulatory influence on food seeking that can be dissociated from that of reward itself; earning a reward and anticipating a reward appear to be distinct processes and have been doubly dissociated at the level of the nucleus accumbens. Furthermore, the excitatory influence of reward-related cues can be both quite specific, based on the identity of the reward anticipated, or more general based on its motivational significance. The influence of these two processes on instrumental actions has also been doubly dissociated at the level of the amygdala. Although the complexity of food seeking provides a hurdle for the treatment of eating disorders, the suggestion that these apparently disparate determinants are functionally integrated within larger neural systems may provide novel approaches to these problems.

  3. Neural circuits for long-term water-reward memory processing in thirsty Drosophila.

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    Shyu, Wei-Huan; Chiu, Tai-Hsiang; Chiang, Meng-Hsuan; Cheng, Yu-Chin; Tsai, Ya-Lun; Fu, Tsai-Feng; Wu, Tony; Wu, Chia-Lin

    2017-05-15

    The intake of water is important for the survival of all animals and drinking water can be used as a reward in thirsty animals. Here we found that thirsty Drosophila melanogaster can associate drinking water with an odour to form a protein-synthesis-dependent water-reward long-term memory (LTM). Furthermore, we found that the reinforcement of LTM requires water-responsive dopaminergic neurons projecting to the restricted region of mushroom body (MB) β' lobe, which are different from the neurons required for the reinforcement of learning and short-term memory (STM). Synaptic output from α'β' neurons is required for consolidation, whereas the output from γ and αβ neurons is required for the retrieval of LTM. Finally, two types of MB efferent neurons retrieve LTM from γ and αβ neurons by releasing glutamate and acetylcholine, respectively. Our results therefore cast light on the cellular and molecular mechanisms responsible for processing water-reward LTM in Drosophila.

  4. Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder.

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    Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

    2017-01-01

    Neuroimaging studies have demonstrated that major depressive disorder (MDD) patients show blunted activity responses to reward-related tasks. However, whether abnormal reward circuits affect cognition and depression in MDD patients remains unclear. Seventy-five drug-naive MDD patients and 42 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. The bilateral nucleus accumbens (NAc) were selected as seeds to construct reward circuits across all subjects. A multivariate linear regression analysis was employed to investigate the neural substrates of cognitive function and depression severity on the reward circuits in MDD patients. The common pathway underlying cognitive deficits and depression was identified with conjunction analysis. Compared with CN subjects, MDD patients showed decreased reward network connectivity that was primarily located in the prefrontal-striatal regions. Importantly, distinct and common neural pathways underlying cognition and depression were identified, implying the independent and synergistic effects of cognitive deficits and depression severity on reward circuits. This study demonstrated that disrupted topological organization within reward circuits was significantly associated with cognitive deficits and depression severity in MDD patients. These findings suggest that in addition to antidepressant treatment, normalized reward circuits should be a focus and a target for improving depression and cognitive deficits in MDD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Neural processing of reward in adolescent rodents

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    Nicholas W. Simon

    2015-02-01

    Full Text Available Immaturities in adolescent reward processing are thought to contribute to poor decision making and increased susceptibility to develop addictive and psychiatric disorders. Very little is known; however, about how the adolescent brain processes reward. The current mechanistic theories of reward processing are derived from adult models. Here we review recent research focused on understanding of how the adolescent brain responds to rewards and reward-associated events. A critical aspect of this work is that age-related differences are evident in neuronal processing of reward-related events across multiple brain regions even when adolescent rats demonstrate behavior similar to adults. These include differences in reward processing between adolescent and adult rats in orbitofrontal cortex and dorsal striatum. Surprisingly, minimal age related differences are observed in ventral striatum, which has been a focal point of developmental studies. We go on to discuss the implications of these differences for behavioral traits affected in adolescence, such as impulsivity, risk-taking, and behavioral flexibility. Collectively, this work suggests that reward-evoked neural activity differs as a function of age and that regions such as the dorsal striatum that are not traditionally associated with affective processing in adults may be critical for reward processing and psychiatric vulnerability in adolescents.

  6. Complexity and competition in appetitive and aversive neural circuits

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    Crista L. Barberini

    2012-11-01

    Full Text Available Decision-making often involves using sensory cues to predict possible rewarding or punishing reinforcement outcomes before selecting a course of action. Recent work has revealed complexity in how the brain learns to predict rewards and punishments. Analysis of neural signaling during and after learning in the amygdala and orbitofrontal cortex, two brain areas that process appetitive and aversive stimuli, reveals a dynamic relationship between appetitive and aversive circuits. Specifically, the relationship between signaling in appetitive and aversive circuits in these areas shifts as a function of learning. Furthermore, although appetitive and aversive circuits may often drive opposite behaviors – approaching or avoiding reinforcement depending upon its valence – these circuits can also drive similar behaviors, such as enhanced arousal or attention; these processes also may influence choice behavior. These data highlight the formidable challenges ahead in dissecting how appetitive and aversive neural circuits interact to produce a complex and nuanced range of behaviors.

  7. The neural correlates of temporal reward discounting.

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    Scheres, Anouk; de Water, Erik; Mies, Gabry W

    2013-09-01

    Temporal reward discounting (TD) refers to the decrease in subjective value of a reward when the delay to that reward increases. In recent years, a growing number of studies on the neural correlates of temporal reward discounting have been conducted. This article focuses on functional magnetic resonance imaging (fMRI) studies on TD in humans. First, we describe the different types of tasks (also from behavioral studies) and the dependent variables. Subsequently, we discuss the evidence for three neurobiological models of TD: the dual-systems model, the single-system model and the self-control model. Further, studies in which nontraditional tasks (e.g., with nonmonetary rewards) were used to study TD are reviewed. Finally, we discuss the neural correlates of individual differences in discounting, and its development across the lifespan. We conclude that the evidence for each of the three neurobiological models of TD is mixed, in that all models receive (partial) support, and several studies provide support for multiple models. Because of large differences between studies in task design and analytical approach, it is difficult to draw a firm conclusion regarding which model provides the best explanation of the neural correlates of temporal discounting. We propose that some components of these models can complement each other, and future studies should test the predictions offered by different models against each other. Several future research directions are suggested, including studying the connectivity between brain regions in relation to discounting, and directly comparing the neural mechanisms involved in discounting of monetary and primary rewards. WIREs Cogn Sci 2013, 4:523-545. doi: 10.1002/wcs.1246 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.

  8. Neural sensitivity to absolute and relative anticipated reward in adolescents.

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    Vaidya, Jatin G; Knutson, Brian; O'Leary, Daniel S; Block, Robert I; Magnotta, Vincent

    2013-01-01

    Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID) task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards). This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude). While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing), adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards) correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity.

  9. Neural sensitivity to absolute and relative anticipated reward in adolescents.

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    Jatin G Vaidya

    Full Text Available Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards. This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude. While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing, adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity.

  10. Flavor vs Energy Sensing in Brain Reward Circuits

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    Ivan E De Araujo

    2014-07-01

    manifestation ranges from flies to rodents and to humans. Future research must determine the molecular and circuit bases for the existence of a sugar-monitoring system at the service of mammal reward neural pathways.

  11. Differentiating neural reward responsiveness in autism versus ADHD

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    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.

  12. Positive mood enhances reward-related neural activity.

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    Young, Christina B; Nusslock, Robin

    2016-06-01

    Although behavioral research has shown that positive mood leads to desired outcomes in nearly every major life domain, no studies have directly examined the effects of positive mood on the neural processes underlying reward-related affect and goal-directed behavior. To address this gap, participants in the present fMRI study experienced either a positive (n = 20) or neutral (n = 20) mood induction and subsequently completed a monetary incentive delay task that assessed reward and loss processing. Consistent with prediction, positive mood elevated activity specifically during reward anticipation in corticostriatal neural regions that have been implicated in reward processing and goal-directed behavior, including the nucleus accumbens, caudate, lateral orbitofrontal cortex and putamen, as well as related paralimbic regions, including the anterior insula and ventromedial prefrontal cortex. These effects were not observed during reward outcome, loss anticipation or loss outcome. Critically, this is the first study to report that positive mood enhances reward-related neural activity. Our findings have implications for uncovering the neural mechanisms by which positive mood enhances goal-directed behavior, understanding the malleability of reward-related neural activity, and developing targeted treatments for psychiatric disorders characterized by deficits in reward processing. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Adaptive neural reward processing during anticipation and receipt of monetary rewards in mindfulness meditators.

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    Kirk, Ulrich; Brown, Kirk Warren; Downar, Jonathan

    2015-05-01

    Reward seeking is ubiquitous and adaptive in humans. But excessive reward seeking behavior, such as chasing monetary rewards, may lead to diminished subjective well-being. This study examined whether individuals trained in mindfulness meditation show neural evidence of lower susceptibility to monetary rewards. Seventy-eight participants (34 meditators, 44 matched controls) completed the monetary incentive delay task while undergoing functional magnetic resonance imaging. The groups performed equally on the task, but meditators showed lower neural activations in the caudate nucleus during reward anticipation, and elevated bilateral posterior insula activation during reward anticipation. Meditators also evidenced reduced activations in the ventromedial prefrontal cortex during reward receipt compared with controls. Connectivity parameters between the right caudate and bilateral anterior insula were attenuated in meditators during incentive anticipation. In summary, brain regions involved in reward processing-both during reward anticipation and receipt of reward-responded differently in mindfulness meditators than in nonmeditators, indicating that the former are less susceptible to monetary incentives. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning.

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    Kim, Sang Hee; Yoon, HeungSik; Kim, Hackjin; Hamann, Stephan

    2015-09-01

    In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

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    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.

  16. Neural processing of reward magnitude under varying attentional demands.

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    Stoppel, Christian Michael; Boehler, Carsten Nicolas; Strumpf, Hendrik; Heinze, Hans-Jochen; Hopf, Jens-Max; Schoenfeld, Mircea Ariel

    2011-04-06

    Central to the organization of behavior is the ability to represent the magnitude of a prospective reward and the costs related to obtaining it. Therein, reward-related neural activations are discounted in dependence of the effort required to resolve a given task. Varying attentional demands of the task might however affect reward-related neural activations. Here we employed fMRI to investigate the neural representation of expected values during a monetary incentive delay task with varying attentional demands. Following a cue, indicating at the same time the difficulty (hard/easy) and the reward magnitude (high/low) of the upcoming trial, subjects performed an attention task and subsequently received feedback about their monetary reward. Consistent with previous results, activity in anterior-cingulate, insular/orbitofrontal and mesolimbic regions co-varied with the anticipated reward-magnitude, but also with the attentional requirements of the task. These activations occurred contingent on action-execution and resembled the response time pattern of the subjects. In contrast, cue-related activations, signaling the forthcoming task-requirements, were only observed within attentional control structures. These results suggest that anticipated reward-magnitude and task-related attentional demands are concurrently processed in partially overlapping neural networks of anterior-cingulate, insular/orbitofrontal, and mesolimbic regions. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Neural correlates of reward in autism

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    Schmitz, Nicole; Rubia, Katya; van Amelsvoort, Therese; Daly, Eileen; Smith, Anna; Murphy, Declan G. M.

    2008-01-01

    BACKGROUND: Lack of social interaction, which is characteristically seen in people with autistic-spectrum disorder, may be caused by malfunctioning of the frontostriatal reward systems. However, no reported in vivo brain imaging studies have investigated reward mechanisms in autistic-spectrum

  18. Overlapping neural systems represent cognitive effort and reward anticipation.

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    Eliana Vassena

    Full Text Available Anticipating a potential benefit and how difficult it will be to obtain it are valuable skills in a constantly changing environment. In the human brain, the anticipation of reward is encoded by the Anterior Cingulate Cortex (ACC and Striatum. Naturally, potential rewards have an incentive quality, resulting in a motivational effect improving performance. Recently it has been proposed that an upcoming task requiring effort induces a similar anticipation mechanism as reward, relying on the same cortico-limbic network. However, this overlapping anticipatory activity for reward and effort has only been investigated in a perceptual task. Whether this generalizes to high-level cognitive tasks remains to be investigated. To this end, an fMRI experiment was designed to investigate anticipation of reward and effort in cognitive tasks. A mental arithmetic task was implemented, manipulating effort (difficulty, reward, and delay in reward delivery to control for temporal confounds. The goal was to test for the motivational effect induced by the expectation of bigger reward and higher effort. The results showed that the activation elicited by an upcoming difficult task overlapped with higher reward prospect in the ACC and in the striatum, thus highlighting a pivotal role of this circuit in sustaining motivated behavior.

  19. Astrocytes: Tailored to Support the Demand of Neural Circuits?

    DEFF Research Database (Denmark)

    Rasmussen, Rune

    2017-01-01

    Anatomy, physiology, proteomics, and genomics reveal the prospect of distinct highly specialized astrocyte subtypes within neural circuits.......Anatomy, physiology, proteomics, and genomics reveal the prospect of distinct highly specialized astrocyte subtypes within neural circuits....

  20. Enhanced neural responsiveness to reward associated with obesity in the absence of food-related stimuli.

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    Opel, Nils; Redlich, Ronny; Grotegerd, Dominik; Dohm, Katharina; Haupenthal, Cordula; Heindel, Walter; Kugel, Harald; Arolt, Volker; Dannlowski, Udo

    2015-06-01

    Obesity has been characterized by alterations in brain structure and function associated with emotion processing and regulation. Particularly, aberrations in food-related reward processing have been frequently demonstrated in obese subjects. However, it remains unclear whether reward-associated functional aberrations in obesity are specific for food-related stimuli or represent a general deficit in reward processing, extending to other stimulus domains. Given the crucial role of rewarding effects in the development of obesity and the ongoing discussion on overlapping neurobiological traits of obesity and psychiatric disorders such as depression and substance-related disorders, this study aimed to investigate the possibility of altered reward processing in obese subjects to occur in the absence of food-related stimuli during a monetary reward condition. Twenty-nine healthy obese subjects (body mass index >30) and 29 healthy, age-, and sex-matched control subjects of normal weight underwent functional MRI during a frequently used card guessing paradigm. A Group × Condition (win vs. loss) ANOVA was conducted to investigate differences between obese and normal-weight subjects. We found significant Group × Condition interaction effects in brain areas involved in emotion regulation and reward processing including the insula, the striatum, and the orbitofrontal cortex (OFC). This interaction was predominantly driven by a significant increase in blood oxygenation level dependent (BOLD) response in obese individuals while experiencing reward. Enhanced neural activation in obesity during reward processing seems to be apparent even in the absence of food-related stimuli and, thus, might point to generalized dysfunctions in reward-related brain circuits in obese individuals. © 2015 Wiley Periodicals, Inc.

  1. Neural reward and punishment sensitivity in cigarette smokers.

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    Potts, Geoffrey F; Bloom, Erika L; Evans, David E; Drobes, David J

    2014-11-01

    Nicotine addiction remains a major public health problem but the neural substrates of addictive behavior remain unknown. One characteristic of smoking behavior is impulsive choice, selecting the immediate reward of smoking despite the potential long-term negative consequences. This suggests that drug users, including cigarette smokers, may be more sensitive to rewards and less sensitive to punishment. We used event-related potentials (ERPs) to test the hypothesis that smokers are more responsive to reward signals and less responsive to punishment, potentially predisposing them to risky behavior. We conducted two experiments, one using a reward prediction design to elicit a Medial Frontal Negativity (MFN) and one using a reward- and punishment-motivated flanker task to elicit an Error Related Negativity (ERN), ERP components thought to index activity in the cortical projection of the dopaminergic reward system. The smokers had a greater MFN response to unpredicted rewards, and non-smokers, but not smokers, had a larger ERN on punishment motivated trials indicating that smokers are more reward sensitive and less punishment sensitive than nonsmokers, overestimating the appetitive value and underestimating aversive outcomes of stimuli and actions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Reward-related neural responses are dependent on the beneficiary.

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    Braams, Barbara R; Güroğlu, Berna; de Water, Erik; Meuwese, Rosa; Koolschijn, P Cédric; Peper, Jiska S; Crone, Eveline A

    2014-07-01

    Prior studies have suggested that positive social interactions are experienced as rewarding. Yet, it is not well understood how social relationships influence neural responses to other persons' gains. In this study, we investigated neural responses during a gambling task in which healthy participants (N = 31; 18 females) could win or lose money for themselves, their best friend or a disliked other (antagonist). At the moment of receiving outcome, person-related activity was observed in the dorsal medial prefrontal cortex (dmPFC), precuneus and temporal parietal junction (TPJ), showing higher activity for friends and antagonists than for self, and this activity was independent of outcome. The only region showing an interaction between the person-participants played for and outcome was the ventral striatum. Specifically, the striatum was more active following gains than losses for self and friends, whereas for the antagonist this pattern was reversed. Together, these results show that, in a context with social and reward information, social aspects are processed in brain regions associated with social cognition (mPFC, TPJ), and reward aspects are processed in primary reward areas (striatum). Furthermore, there is an interaction of social and reward information in the striatum, such that reward-related activity was dependent on social relationship. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  3. Document analysis with neural net circuits

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    Graf, Hans Peter

    1994-01-01

    Document analysis is one of the main applications of machine vision today and offers great opportunities for neural net circuits. Despite more and more data processing with computers, the number of paper documents is still increasing rapidly. A fast translation of data from paper into electronic format is needed almost everywhere, and when done manually, this is a time consuming process. Markets range from small scanners for personal use to high-volume document analysis systems, such as address readers for the postal service or check processing systems for banks. A major concern with present systems is the accuracy of the automatic interpretation. Today's algorithms fail miserably when noise is present, when print quality is poor, or when the layout is complex. A common approach to circumvent these problems is to restrict the variations of the documents handled by a system. In our laboratory, we had the best luck with circuits implementing basic functions, such as convolutions, that can be used in many different algorithms. To illustrate the flexibility of this approach, three applications of the NET32K circuit are described in this short viewgraph presentation: locating address blocks, cleaning document images by removing noise, and locating areas of interest in personal checks to improve image compression. Several of the ideas realized in this circuit that were inspired by neural nets, such as analog computation with a low resolution, resulted in a chip that is well suited for real-world document analysis applications and that compares favorably with alternative, 'conventional' circuits.

  4. Reward-based training of recurrent neural networks for cognitive and value-based tasks

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    Song, H Francis; Yang, Guangyu R; Wang, Xiao-Jing

    2017-01-01

    Trained neural network models, which exhibit features of neural activity recorded from behaving animals, may provide insights into the circuit mechanisms of cognitive functions through systematic analysis of network activity and connectivity. However, in contrast to the graded error signals commonly used to train networks through supervised learning, animals learn from reward feedback on definite actions through reinforcement learning. Reward maximization is particularly relevant when optimal behavior depends on an animal’s internal judgment of confidence or subjective preferences. Here, we implement reward-based training of recurrent neural networks in which a value network guides learning by using the activity of the decision network to predict future reward. We show that such models capture behavioral and electrophysiological findings from well-known experimental paradigms. Our work provides a unified framework for investigating diverse cognitive and value-based computations, and predicts a role for value representation that is essential for learning, but not executing, a task. DOI: http://dx.doi.org/10.7554/eLife.21492.001 PMID:28084991

  5. Fairness influences early signatures of reward-related neural processing.

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    Massi, Bart; Luhmann, Christian C

    2015-12-01

    Many humans exhibit a strong preference for fairness during decision-making. Although there is evidence that social factors influence reward-related and affective neural processing, it is unclear if this effect is mediated by compulsory outcome evaluation processes or results from slower deliberate cognition. Here we show that the feedback-related negativity (FRN) and late positive potential (LPP), two signatures of early hedonic processing, are modulated by the fairness of rewards during a passive rating task. We find that unfair payouts elicit larger FRNs than fair payouts, whereas fair payouts elicit larger LPPs than unfair payouts. This is true both in the time-domain, where the FRN and LPP are related, and in the time-frequency domain, where the two signals are largely independent. Ultimately, this work demonstrates that fairness affects the early stages of reward and affective processing, suggesting a common biological mechanism for social and personal reward evaluation.

  6. I can't wait! Neural reward signals in impulsive individuals exaggerate the difference between immediate and future rewards.

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    Schmidt, Barbara; Holroyd, Clay B; Debener, Stefan; Hewig, Johannes

    2017-03-01

    Waiting for rewards is difficult, and highly impulsive individuals with low self-control have an especially hard time with it. Here, we investigated whether neural responses to rewards in a delayed gratification task predict impulsivity and self-control. The EEG was recorded from participants engaged in a guessing game in which on each trial they could win either a large or small reward, paid either now or after 6 months. Ratings confirmed that participants preferred immediate, large rewards over small, delayed rewards. Electrophysiological reward signals reflecting the difference between immediate and future rewards predicted self-report measures of impulsivity and self-control. Further, these signals were highly reliable across two sessions over a 1-week interval, showing high temporal stability like stable personality traits. These results suggest that greater valuation of immediate rewards causes impulsive individuals to redirect control away from delayed rewards, indicating why it is so hard for them to wait. © 2016 Society for Psychophysiological Research.

  7. Separate neural systems value immediate and delayed monetary rewards.

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    McClure, Samuel M; Laibson, David I; Loewenstein, George; Cohen, Jonathan D

    2004-10-15

    When humans are offered the choice between rewards available at different points in time, the relative values of the options are discounted according to their expected delays until delivery. Using functional magnetic resonance imaging, we examined the neural correlates of time discounting while subjects made a series of choices between monetary reward options that varied by delay to delivery. We demonstrate that two separate systems are involved in such decisions. Parts of the limbic system associated with the midbrain dopamine system, including paralimbic cortex, are preferentially activated by decisions involving immediately available rewards. In contrast, regions of the lateral prefrontal cortex and posterior parietal cortex are engaged uniformly by intertemporal choices irrespective of delay. Furthermore, the relative engagement of the two systems is directly associated with subjects' choices, with greater relative fronto-parietal activity when subjects choose longer term options.

  8. Robust information propagation through noisy neural circuits.

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    Zylberberg, Joel; Pouget, Alexandre; Latham, Peter E; Shea-Brown, Eric

    2017-04-01

    Sensory neurons give highly variable responses to stimulation, which can limit the amount of stimulus information available to downstream circuits. Much work has investigated the factors that affect the amount of information encoded in these population responses, leading to insights about the role of covariability among neurons, tuning curve shape, etc. However, the informativeness of neural responses is not the only relevant feature of population codes; of potentially equal importance is how robustly that information propagates to downstream structures. For instance, to quantify the retina's performance, one must consider not only the informativeness of the optic nerve responses, but also the amount of information that survives the spike-generating nonlinearity and noise corruption in the next stage of processing, the lateral geniculate nucleus. Our study identifies the set of covariance structures for the upstream cells that optimize the ability of information to propagate through noisy, nonlinear circuits. Within this optimal family are covariances with "differential correlations", which are known to reduce the information encoded in neural population activities. Thus, covariance structures that maximize information in neural population codes, and those that maximize the ability of this information to propagate, can be very different. Moreover, redundancy is neither necessary nor sufficient to make population codes robust against corruption by noise: redundant codes can be very fragile, and synergistic codes can-in some cases-optimize robustness against noise.

  9. Robust information propagation through noisy neural circuits.

    Directory of Open Access Journals (Sweden)

    Joel Zylberberg

    2017-04-01

    Full Text Available Sensory neurons give highly variable responses to stimulation, which can limit the amount of stimulus information available to downstream circuits. Much work has investigated the factors that affect the amount of information encoded in these population responses, leading to insights about the role of covariability among neurons, tuning curve shape, etc. However, the informativeness of neural responses is not the only relevant feature of population codes; of potentially equal importance is how robustly that information propagates to downstream structures. For instance, to quantify the retina's performance, one must consider not only the informativeness of the optic nerve responses, but also the amount of information that survives the spike-generating nonlinearity and noise corruption in the next stage of processing, the lateral geniculate nucleus. Our study identifies the set of covariance structures for the upstream cells that optimize the ability of information to propagate through noisy, nonlinear circuits. Within this optimal family are covariances with "differential correlations", which are known to reduce the information encoded in neural population activities. Thus, covariance structures that maximize information in neural population codes, and those that maximize the ability of this information to propagate, can be very different. Moreover, redundancy is neither necessary nor sufficient to make population codes robust against corruption by noise: redundant codes can be very fragile, and synergistic codes can-in some cases-optimize robustness against noise.

  10. 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.

  11. 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.

  12. Neural correlates of reward and loss sensitivity in psychopathy.

    Science.gov (United States)

    Pujara, Maia; Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

    2014-06-01

    Psychopathy is a personality disorder associated with callous and impulsive behavior and criminal recidivism. It has long been theorized that psychopaths have deficits in processing reward and punishment. Here, we use structural and functional magnetic resonance imaging to examine the neural correlates of reward and loss sensitivity in a group of criminal psychopaths. Forty-one adult male prison inmates (n = 18 psychopaths and n = 23 non-psychopaths) completed a functional magnetic resonance imaging task involving the gain or loss of money. Across the entire sample of participants, monetary gains elicited robust activation within the ventral striatum (VS). Although psychopaths and non-psychopaths did not significantly differ with respect to overall levels of VS response to reward vs loss, we observed significantly different correlations between VS responses and psychopathy severity within each group. Volumetric analyses of striatal subregions revealed a similar pattern of correlations, specifically for the right accumbens area within VS. In a separate sample of inmates (n = 93 psychopaths and n = 117 non-psychopaths) who completed a self-report measure of appetitive motivation, we again found that the correlation with psychopathy severity differed between groups. These convergent results offer novel insight into the neural substrates of reward and loss processing in psychopathy. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity.

    Science.gov (United States)

    van Rijn, Inge; Griffioen-Roose, Sanne; de Graaf, Cees; Smeets, Paul A M

    2015-01-01

    A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth and trait reward sensitivity in different hunger states. Firstly, we assessed this in data from a functional neuroimaging study (van Rijn et al., 2015), in which participants (n = 30) tasted simple solutions of a non-caloric sweetener with or without a non-sweet carbohydrate (maltodextrin) during hunger and satiety. Secondly, we expanded these analyses to regular drinks by assessing the same relationship in data from a study in which soft drinks sweetened with either sucrose or a non-caloric sweetener were administered during hunger (n = 18) (Griffioen-Roose et al., 2013). First, taste activation by the non-caloric solution/soft drink was subtracted from that by the caloric solution/soft drink to eliminate sweetness effects and retain activation induced by calories. Subsequently, this difference in taste activation was correlated with reward sensitivity as measured with the BAS drive subscale of the Behavioral Activation System (BAS) questionnaire. When participants were hungry and tasted calories from the simple solution, brain activation in the right ventral striatum (caudate), right amygdala and anterior cingulate cortex (bilaterally) correlated negatively with BAS drive scores. In contrast, when participants were satiated, taste responses correlated positively with BAS drive scores in the left caudate. These results were not replicated for soft drinks. Thus, neural responses to oral calories from maltodextrin were modulated by reward sensitivity in reward-related brain areas. This was not the case for sucrose. This may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. Also, in a familiar beverage, detection of calories per se may be

  14. Neural circuit mechanisms of posttraumatic epilepsy

    Directory of Open Access Journals (Sweden)

    Robert F Hunt

    2013-06-01

    Full Text Available Traumatic brain injury (TBI greatly increases the risk for a number of mental health problems and is one of the most common causes of medically intractable epilepsy in humans. Several models of TBI have been developed to investigate the relationship between trauma, seizures, and epilepsy-related changes in neural circuit function. These studies have shown that the brain initiates immediate neuronal and glial responses following an injury, usually leading to significant cell loss in areas of the injured brain. Over time, long-term changes in the organization of neural circuits, particularly in neocortex and hippocampus, lead to an imbalance between excitatory and inhibitory neurotransmission and increased risk for spontaneous seizures. These include alterations to inhibitory interneurons and formation of new, excessive recurrent excitatory synaptic connectivity. Here, we review in vivo models of TBI as well as key cellular mechanisms of synaptic reorganization associated with posttraumatic epilepsy. The potential role of inflammation and increased blood brain barrier permeability in the pathophysiology of posttraumatic epilepsy is also discussed. A better understanding of mechanisms that promote the generation of epileptic activity versus those that promote compensatory brain repair and functional recovery should aid development of successful new therapies for posttraumatic epilepsy.

  15. Marginalization in neural circuits with divisive normalization

    Science.gov (United States)

    Beck, J.M.; Latham, P.E.; Pouget, A.

    2011-01-01

    A wide range of computations performed by the nervous system involves a type of probabilistic inference known as marginalization. This computation comes up in seemingly unrelated tasks, including causal reasoning, odor recognition, motor control, visual tracking, coordinate transformations, visual search, decision making, and object recognition, to name just a few. The question we address here is: how could neural circuits implement such marginalizations? We show that when spike trains exhibit a particular type of statistics – associated with constant Fano factors and gain-invariant tuning curves, as is often reported in vivo – some of the more common marginalizations can be achieved with networks that implement a quadratic nonlinearity and divisive normalization, the latter being a type of nonlinear lateral inhibition that has been widely reported in neural circuits. Previous studies have implicated divisive normalization in contrast gain control and attentional modulation. Our results raise the possibility that it is involved in yet another, highly critical, computation: near optimal marginalization in a remarkably wide range of tasks. PMID:22031877

  16. Explicit logic circuits discriminate neural states.

    Directory of Open Access Journals (Sweden)

    Lane Yoder

    Full Text Available The magnitude and apparent complexity of the brain's connectivity have left explicit networks largely unexplored. As a result, the relationship between the organization of synaptic connections and how the brain processes information is poorly understood. A recently proposed retinal network that produces neural correlates of color vision is refined and extended here to a family of general logic circuits. For any combination of high and low activity in any set of neurons, one of the logic circuits can receive input from the neurons and activate a single output neuron whenever the input neurons have the given activity state. The strength of the output neuron's response is a measure of the difference between the smallest of the high inputs and the largest of the low inputs. The networks generate correlates of known psychophysical phenomena. These results follow directly from the most cost-effective architectures for specific logic circuits and the minimal cellular capabilities of excitation and inhibition. The networks function dynamically, making their operation consistent with the speed of most brain functions. The networks show that well-known psychophysical phenomena do not require extraordinarily complex brain structures, and that a single network architecture can produce apparently disparate phenomena in different sensory systems.

  17. Intelligence moderates neural responses to monetary reward and punishment.

    Science.gov (United States)

    Hawes, Daniel R; DeYoung, Colin G; Gray, Jeremy R; Rustichini, Aldo

    2014-05-01

    The relations between intelligence (IQ) and neural responses to monetary gains and losses were investigated in a simple decision task. In 94 healthy adults, typical responses of striatal blood oxygen level-dependent (BOLD) signal after monetary reward and punishment were weaker for subjects with higher IQ. IQ-moderated differential responses to gains and losses were also found for regions in the medial prefrontal cortex, posterior cingulate cortex, and left inferior frontal cortex. These regions have previously been identified with the subjective utility of monetary outcomes. Analysis of subjects' behavior revealed a correlation between IQ and the extent to which choices were related to experienced decision outcomes in preceding trials. Specifically, higher IQ predicted behavior to be more strongly correlated with an extended period of previously experienced decision outcomes, whereas lower IQ predicted behavior to be correlated exclusively to the most recent decision outcomes. We link these behavioral and imaging findings to a theoretical model capable of describing a role for intelligence during the evaluation of rewards generated by unknown probabilistic processes. Our results demonstrate neural differences in how people of different intelligence respond to experienced monetary rewards and punishments. Our theoretical discussion offers a functional description for how these individual differences may be linked to choice behavior. Together, our results and model support the hypothesis that observed correlations between intelligence and preferences may be rooted in the way decision outcomes are experienced ex post, rather than deriving exclusively from how choices are evaluated ex ante.

  18. Neural correlates of reward-based spatial learning in persons with cocaine dependence.

    Science.gov (United States)

    Tau, Gregory Z; Marsh, Rachel; Wang, Zhishun; Torres-Sanchez, Tania; Graniello, Barbara; Hao, Xuejun; Xu, Dongrong; Packard, Mark G; Duan, Yunsuo; Kangarlu, Alayar; Martinez, Diana; Peterson, Bradley S

    2014-02-01

    Dysfunctional learning systems are thought to be central to the pathogenesis of and impair recovery from addictions. The functioning of the brain circuits for episodic memory or learning that support goal-directed behavior has not been studied previously in persons with cocaine dependence (CD). Thirteen abstinent CD and 13 healthy participants underwent MRI scanning while performing a task that requires the use of spatial cues to navigate a virtual-reality environment and find monetary rewards, allowing the functional assessment of the brain systems for spatial learning, a form of episodic memory. Whereas both groups performed similarly on the reward-based spatial learning task, we identified disturbances in brain regions involved in learning and reward in CD participants. In particular, CD was associated with impaired functioning of medial temporal lobe (MTL), a brain region that is crucial for spatial learning (and episodic memory) with concomitant recruitment of striatum (which normally participates in stimulus-response, or habit, learning), and prefrontal cortex. CD was also associated with enhanced sensitivity of the ventral striatum to unexpected rewards but not to expected rewards earned during spatial learning. We provide evidence that spatial learning in CD is characterized by disturbances in functioning of an MTL-based system for episodic memory and a striatum-based system for stimulus-response learning and reward. We have found additional abnormalities in distributed cortical regions. Consistent with findings from animal studies, we provide the first evidence in humans describing the disruptive effects of cocaine on the coordinated functioning of multiple neural systems for learning and memory.

  19. When "Your" reward is the same as "My" reward: self-construal priming shifts neural responses to own vs. friends' rewards.

    Science.gov (United States)

    Varnum, Michael E W; Shi, Zhenhao; Chen, Antao; Qiu, Jiang; Han, Shihui

    2014-02-15

    Is it possible for neural responses to others' rewards to be as strong as those for the self? Although prior fMRI studies have demonstrated that watching others get rewards can activate one's own reward centers, such vicarious reward activation has always been less strong than responses to rewards for oneself. In the present study we manipulated participants' self-construal (independent vs. interdependent) and found that, when an independent self-construal was primed, subjects showed greater activation in the bilateral ventral striatum in response to winning money for the self (vs. for a friend) during a gambling game. However, priming an interdependent self-construal resulted in comparable activation in these regions in response to winning money for the self and for a friend. Our findings suggest that interdependence may cause people to experience rewards for a close other as strongly as they experience rewards for the self. © 2013 Elsevier Inc. All rights reserved.

  20. Favorite brands as cultural objects modulate reward circuit.

    Science.gov (United States)

    Schaefer, Michael; Rotte, Michael

    2007-01-22

    On the basis of the hypothesis that brands may function as reward stimuli, we investigated brain responses to favorite brands. Participants viewed brand logos while we measured cortical activity with functional magnetic resonance imaging. Results revealed activity in the striatum for favorite brands that positively correlated with sports and luxury characteristics, but negatively with attributions to a brand of rational choice. Reduced activation of a single region in the dorsolateral prefrontal cortex was demonstrated when viewing the most beloved brand, possibly suggesting reduced strategic reasoning on the basis of affect. The results propose that brands that have been associated with appetitive stimuli owing to marketing efforts engage brain networks similar to those engaged by artificially associated reward stimuli. Moreover, social stimuli may function as secondary inducers of reward mechanisms.

  1. Motivated To Win: Relationship between Anticipatory and Outcome Reward-Related Neural Activity

    Science.gov (United States)

    Nusslock, Robin

    2015-01-01

    Reward-processing involves two temporal stages characterized by two distinct neural processes: reward-anticipation and reward-outcome. Intriguingly, very little research has examined the relationship between neural processes involved in reward-anticipation and reward-outcome. To investigate this, one needs to consider the heterogeneity of reward-processing within each stage. To identify different stages of reward processing, we adapted a reward time-estimation task. While EEG data were recorded, participants were instructed to button-press 3.5 s after the onset of an Anticipation-Cue and received monetary reward for good time-estimation on the Reward trials, but not on No-Reward trials. We first separated reward-anticipation into event related potentials (ERPs) occurring at three sub-stages: reward/no-reward cue-evaluation, motor-preparation and feedback-anticipation. During reward/no-reward cue-evaluation, the Reward-Anticipation Cue led to a smaller N2 and larger P3. During motor-preparation, we report, for the first time, that the Reward-Anticipation Cue enhanced the Readiness Potential (RP), starting approximately 1 s before movement. At the subsequent feedback-anticipation stage, the Reward-Anticipation Cue elevated the Stimulus-Preceding Negativity (SPN). We also separated reward-outcome ERPs into different components occurring at different time-windows: the Feedback-Related Negativity (FRN), Feedback-P3 (FB-P3) and Late-Positive Potentials (LPP). Lastly, we examined the relationship between reward-anticipation and reward-outcome ERPs. We report that individual-differences in specific reward-anticipation ERPs uniquely predicted specific reward-outcome ERPs. In particular, the reward-anticipation Early-RP (1 to .8 s before movement) predicted early reward-outcome ERPs (FRN and FB-P3), whereas, the reward-anticipation SPN most strongly predicted a later reward-outcome ERP (LPP). Results have important implications for understanding the nature of the

  2. Motivated to win: Relationship between anticipatory and outcome reward-related neural activity.

    Science.gov (United States)

    Pornpattananangkul, Narun; Nusslock, Robin

    2015-11-01

    Reward-processing involves two temporal stages characterized by two distinct neural processes: reward-anticipation and reward-outcome. Intriguingly, very little research has examined the relationship between neural processes involved in reward-anticipation and reward-outcome. To investigate this, one needs to consider the heterogeneity of reward-processing within each stage. To identify different stages of reward processing, we adapted a reward time-estimation task. While EEG data were recorded, participants were instructed to button-press 3.5s after the onset of an Anticipation-Cue and received monetary reward for good time-estimation on the Reward trials, but not on No-Reward trials. We first separated reward-anticipation into event related potentials (ERPs) occurring at three sub-stages: reward/no-reward cue-evaluation, motor-preparation and feedback-anticipation. During reward/no-reward cue-evaluation, the Reward-Anticipation Cue led to a smaller N2 and larger P3. During motor-preparation, we report, for the first time, that the Reward-Anticipation Cue enhanced the Readiness Potential (RP), starting approximately 1s before movement. At the subsequent feedback-anticipation stage, the Reward-Anticipation Cue elevated the Stimulus-Preceding Negativity (SPN). We also separated reward-outcome ERPs into different components occurring at different time-windows: the Feedback-Related Negativity (FRN), Feedback-P3 (FB-P3) and Late-Positive Potentials (LPP). Lastly, we examined the relationship between reward-anticipation and reward-outcome ERPs. We report that individual-differences in specific reward-anticipation ERPs uniquely predicted specific reward-outcome ERPs. In particular, the reward-anticipation Early-RP (1-.8s before movement) predicted early reward-outcome ERPs (FRN and FB-P3), whereas, the reward-anticipation SPN most strongly predicted a later reward-outcome ERP (LPP). Results have important implications for understanding the nature of the relationship

  3. Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology.

    Science.gov (United States)

    Schultz, Wolfram

    2004-04-01

    Neurons in a small number of brain structures detect rewards and reward-predicting stimuli and are active during the expectation of predictable food and liquid rewards. These neurons code the reward information according to basic terms of various behavioural theories that seek to explain reward-directed learning, approach behaviour and decision-making. The involved brain structures include groups of dopamine neurons, the striatum including the nucleus accumbens, the orbitofrontal cortex and the amygdala. The reward information is fed to brain structures involved in decision-making and organisation of behaviour, such as the dorsolateral prefrontal cortex and possibly the parietal cortex. The neural coding of basic reward terms derived from formal theories puts the neurophysiological investigation of reward mechanisms on firm conceptual grounds and provides neural correlates for the function of rewards in learning, approach behaviour and decision-making.

  4. How instructed knowledge modulates the neural systems of reward learning.

    Science.gov (United States)

    Li, Jian; Delgado, Mauricio R; Phelps, Elizabeth A

    2011-01-04

    Recent research in neuroeconomics has demonstrated that the reinforcement learning model of reward learning captures the patterns of both behavioral performance and neural responses during a range of economic decision-making tasks. However, this powerful theoretical model has its limits. Trial-and-error is only one of the means by which individuals can learn the value associated with different decision options. Humans have also developed efficient, symbolic means of communication for learning without the necessity for committing multiple errors across trials. In the present study, we observed that instructed knowledge of cue-reward probabilities improves behavioral performance and diminishes reinforcement learning-related blood-oxygen level-dependent (BOLD) responses to feedback in the nucleus accumbens, ventromedial prefrontal cortex, and hippocampal complex. The decrease in BOLD responses in these brain regions to reward-feedback signals was functionally correlated with activation of the dorsolateral prefrontal cortex (DLPFC). These results suggest that when learning action values, participants use the DLPFC to dynamically adjust outcome responses in valuation regions depending on the usefulness of action-outcome information.

  5. Common neural mechanisms underlying reversal learning by reward and punishment.

    Science.gov (United States)

    Xue, Gui; Xue, Feng; Droutman, Vita; Lu, Zhong-Lin; Bechara, Antoine; Read, Stephen

    2013-01-01

    Impairments in flexible goal-directed decisions, often examined by reversal learning, are associated with behavioral abnormalities characterized by impulsiveness and disinhibition. Although the lateral orbital frontal cortex (OFC) has been consistently implicated in reversal learning, it is still unclear whether this region is involved in negative feedback processing, behavioral control, or both, and whether reward and punishment might have different effects on lateral OFC involvement. Using a relatively large sample (N = 47), and a categorical learning task with either monetary reward or moderate electric shock as feedback, we found overlapping activations in the right lateral OFC (and adjacent insula) for reward and punishment reversal learning when comparing correct reversal trials with correct acquisition trials, whereas we found overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when negative feedback signaled contingency change. The right lateral OFC and DLPFC also showed greater sensitivity to punishment than did their left homologues, indicating an asymmetry in how punishment is processed. We propose that the right lateral OFC and anterior insula are important for transforming affective feedback to behavioral adjustment, whereas the right DLPFC is involved in higher level attention control. These results provide insight into the neural mechanisms of reversal learning and behavioral flexibility, which can be leveraged to understand risky behaviors among vulnerable populations.

  6. Reward Motivation Accelerates the Onset of Neural Novelty Signals in Humans to 85 Milliseconds

    National Research Council Canada - National Science Library

    Bunzeck, Nico; Doeller, Christian F; Fuentemilla, Lluis; Dolan, Raymond J; Duzel, Emrah

    2009-01-01

    ... are rewarded [8] . In human recognition memory studies, on the other hand, reward is not used to motivate the detection of novel or familiar items. Remarkably, the possibility that the timing of neural novelty signals might be affected if the discrimination of novel and familiar items is rewarded has not yet been tested. Indeed, novelty proces...

  7. Cross-talk between the epigenome and neural circuits in drug addiction.

    Science.gov (United States)

    Mews, Philipp; Calipari, Erin S

    2017-01-01

    Drug addiction is a behavioral disorder characterized by dysregulated learning about drugs and associated cues that result in compulsive drug seeking and relapse. Learning about drug rewards and predictive cues is a complex process controlled by a computational network of neural connections interacting with transcriptional and molecular mechanisms within each cell to precisely guide behavior. The interplay between rapid, temporally specific neuronal activation, and longer-term changes in transcription is of critical importance in the expression of appropriate, or in the case of drug addiction, inappropriate behaviors. Thus, these factors and their interactions must be considered together, especially in the context of treatment. Understanding the complex interplay between epigenetic gene regulation and circuit connectivity will allow us to formulate novel therapies to normalize maladaptive reward behaviors, with a goal of modulating addictive behaviors, while leaving natural reward-associated behavior unaffected. © 2017 Elsevier B.V. All rights reserved.

  8. A neural circuit for angular velocity computation

    Directory of Open Access Journals (Sweden)

    Samuel B Snider

    2010-12-01

    Full Text Available In one of the most remarkable feats of motor control in the animal world, some Diptera, such as the housefly, can accurately execute corrective flight maneuvers in tens of milliseconds. These reflexive movements are achieved by the halteres, gyroscopic force sensors, in conjunction with rapidly-tunable wing-steering muscles. Specifically, the mechanosensory campaniform sensilla located at the base of the halteres transduce and transform rotation-induced gyroscopic forces into information about the angular velocity of the fly's body. But how exactly does the fly's neural architecture generate the angular velocity from the lateral strain forces on the left and right halteres? To explore potential algorithms, we built a neuro-mechanical model of the rotation detection circuit. We propose a neurobiologically plausible method by which the fly could accurately separate and measure the three-dimensional components of an imposed angular velocity. Our model assumes a single sign-inverting synapse and formally resembles some models of directional selectivity by the retina. Using multidimensional error analysis, we demonstrate the robustness of our model under a variety of input conditions. Our analysis reveals the maximum information available to the fly given its physical architecture and the mathematics governing the rotation-induced forces at the haltere's end knob.

  9. A neural circuit for angular velocity computation.

    Science.gov (United States)

    Snider, Samuel B; Yuste, Rafael; Packer, Adam M

    2010-01-01

    In one of the most remarkable feats of motor control in the animal world, some Diptera, such as the housefly, can accurately execute corrective flight maneuvers in tens of milliseconds. These reflexive movements are achieved by the halteres, gyroscopic force sensors, in conjunction with rapidly tunable wing steering muscles. Specifically, the mechanosensory campaniform sensilla located at the base of the halteres transduce and transform rotation-induced gyroscopic forces into information about the angular velocity of the fly's body. But how exactly does the fly's neural architecture generate the angular velocity from the lateral strain forces on the left and right halteres? To explore potential algorithms, we built a neuromechanical model of the rotation detection circuit. We propose a neurobiologically plausible method by which the fly could accurately separate and measure the three-dimensional components of an imposed angular velocity. Our model assumes a single sign-inverting synapse and formally resembles some models of directional selectivity by the retina. Using multidimensional error analysis, we demonstrate the robustness of our model under a variety of input conditions. Our analysis reveals the maximum information available to the fly given its physical architecture and the mathematics governing the rotation-induced forces at the haltere's end knob.

  10. Dynamical foundations of the neural circuit for bayesian decision making.

    Science.gov (United States)

    Morita, Kenji

    2009-07-01

    On the basis of accumulating behavioral and neural evidences, it has recently been proposed that the brain neural circuits of humans and animals are equipped with several specific properties, which ensure that perceptual decision making implemented by the circuits can be nearly optimal in terms of Bayesian inference. Here, I introduce the basic ideas of such a proposal and discuss its implications from the standpoint of biophysical modeling developed in the framework of dynamical systems.

  11. Neural Control of Energy Balance: Translating Circuits to Therapies

    OpenAIRE

    Gautron, Laurent; Elmquist, Joel K.; Williams, Kevin W.

    2015-01-01

    Recent insights into the neural circuits controlling energy balance and glucose homeostasis have rekindled the hope for development of novel treatments for obesity and diabetes. However, many therapies contribute relatively modest beneficial gains with accompanying side effects, and the mechanisms of action for other interventions remain undefined. This Review summarizes current knowledge linking the neural circuits regulating energy and glucose balance with current and potential pharmacother...

  12. 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

  13. Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity

    NARCIS (Netherlands)

    van Rijn, Inge; Griffioen-Roose, Sanne; de Graaf, Cees; Smeets, Paul A M|info:eu-repo/dai/nl/304817740

    A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth

  14. Fear and Reward Circuit Alterations in Pediatric CRPS.

    Science.gov (United States)

    Simons, Laura E; Erpelding, Nathalie; Hernandez, Jessica M; Serrano, Paul; Zhang, Kunyu; Lebel, Alyssa A; Sethna, Navil F; Berde, Charles B; Prabhu, Sanjay P; Becerra, Lino; Borsook, David

    2015-01-01

    In chronic pain, a number of brain regions involved in emotion (e.g., amygdala, hippocampus, nucleus accumbens, insula, anterior cingulate, and prefrontal cortex) show significant functional and morphometric changes. One phenotypic manifestation of these changes is pain-related fear (PRF). PRF is associated with profoundly altered behavioral adaptations to chronic pain. For example, patients with a neuropathic pain condition known as complex regional pain syndrome (CRPS) often avoid use of and may even neglect the affected body area(s), thus maintaining and likely enhancing PRF. These changes form part of an overall maladaptation to chronic pain. To examine fear-related brain circuit alterations in humans, 20 pediatric patients with CRPS and 20 sex- and age-matched healthy controls underwent functional magnetic resonance imaging (fMRI) in response to a well-established fearful faces paradigm. Despite no significant differences on self-reported emotional valence and arousal between the two groups, CRPS patients displayed a diminished response to fearful faces in regions associated with emotional processing compared to healthy controls. Additionally, increased PRF levels were associated with decreased activity in a number of brain regions including the right amygdala, insula, putamen, and caudate. Blunted activation in patients suggests that (a) individuals with chronic pain may have deficits in cognitive-affective brain circuits that may represent an underlying vulnerability or consequence to the chronic pain state; and (b) fear of pain may contribute and/or maintain these brain alterations. Our results shed new light on altered affective circuits in patients with chronic pain and identify PRF as a potentially important treatment target.

  15. Fear and Reward Circuit Alterations in Pediatric CRPS

    Science.gov (United States)

    Simons, Laura E.; Erpelding, Nathalie; Hernandez, Jessica M.; Serrano, Paul; Zhang, Kunyu; Lebel, Alyssa A.; Sethna, Navil F.; Berde, Charles B.; Prabhu, Sanjay P.; Becerra, Lino; Borsook, David

    2016-01-01

    In chronic pain, a number of brain regions involved in emotion (e.g., amygdala, hippocampus, nucleus accumbens, insula, anterior cingulate, and prefrontal cortex) show significant functional and morphometric changes. One phenotypic manifestation of these changes is pain-related fear (PRF). PRF is associated with profoundly altered behavioral adaptations to chronic pain. For example, patients with a neuropathic pain condition known as complex regional pain syndrome (CRPS) often avoid use of and may even neglect the affected body area(s), thus maintaining and likely enhancing PRF. These changes form part of an overall maladaptation to chronic pain. To examine fear-related brain circuit alterations in humans, 20 pediatric patients with CRPS and 20 sex- and age-matched healthy controls underwent functional magnetic resonance imaging (fMRI) in response to a well-established fearful faces paradigm. Despite no significant differences on self-reported emotional valence and arousal between the two groups, CRPS patients displayed a diminished response to fearful faces in regions associated with emotional processing compared to healthy controls. Additionally, increased PRF levels were associated with decreased activity in a number of brain regions including the right amygdala, insula, putamen, and caudate. Blunted activation in patients suggests that (a) individuals with chronic pain may have deficits in cognitive-affective brain circuits that may represent an underlying vulnerability or consequence to the chronic pain state; and (b) fear of pain may contribute and/or maintain these brain alterations. Our results shed new light on altered affective circuits in patients with chronic pain and identify PRF as a potentially important treatment target. PMID:26834606

  16. Neural dynamics of reward probability coding: a Magnetoencephalographic study in humans

    Directory of Open Access Journals (Sweden)

    Julie eThomas

    2013-11-01

    Full Text Available Prediction of future rewards and discrepancy between actual and expected outcomes (prediction error are crucial signals for adaptive behavior. In humans, a number of fMRI studies demonstrated that reward probability modulates these two signals in a large brain network. Yet, the spatio-temporal dynamics underlying the neural coding of reward probability remains unknown. Here, using magnetoencephalography, we investigated the neural dynamics of prediction and reward prediction error computations while subjects learned to associate cues of slot machines with monetary rewards with different probabilities. We showed that event-related magnetic fields (ERFs arising from the visual cortex coded the expected reward value 155 ms after the cue, demonstrating that reward value signals emerge early in the visual stream. Moreover, a prediction error was reflected in ERF peaking 300 ms after the rewarded outcome and showing decreasing amplitude with higher reward probability. This prediction error signal was generated in a network including the anterior and posterior cingulate cortex. These findings pinpoint the spatio-temporal characteristics underlying reward probability coding. Together, our results provide insights into the neural dynamics underlying the ability to learn probabilistic stimuli-reward contingencies.

  17. Classes of feedforward neural networks and their circuit complexity

    NARCIS (Netherlands)

    Shawe-Taylor, John S.; Anthony, Martin H.G.; Kern, Walter

    1992-01-01

    This paper aims to place neural networks in the context of boolean circuit complexity. We define appropriate classes of feedforward neural networks with specified fan-in, accuracy of computation and depth and using techniques of communication complexity proceed to show that the classes fit into a

  18. Japanese studies on neural circuits and behavior of Caenorhabditis elegans

    Science.gov (United States)

    Sasakura, Hiroyuki; Tsukada, Yuki; Takagi, Shin; Mori, Ikue

    2013-01-01

    The nematode Caenorhabditis elegans is an ideal organism for studying neural plasticity and animal behaviors. A total of 302 neurons of a C. elegans hermaphrodite have been classified into 118 neuronal groups. This simple neural circuit provides a solid basis for understanding the mechanisms of the brains of higher animals, including humans. Recent studies that employ modern imaging and manipulation techniques enable researchers to study the dynamic properties of nervous systems with great precision. Behavioral and molecular genetic analyses of this tiny animal have contributed greatly to the advancement of neural circuit research. Here, we will review the recent studies on the neural circuits of C. elegans that have been conducted in Japan. Several laboratories have established unique and clever methods to study the underlying neuronal substrates of behavioral regulation in C. elegans. The technological advances applied to studies of C. elegans have allowed new approaches for the studies of complex neural systems. Through reviewing the studies on the neuronal circuits of C. elegans in Japan, we will analyze and discuss the directions of neural circuit studies. PMID:24348340

  19. Mapping brain circuits of reward and motivation: in the footsteps of Ann Kelley.

    Science.gov (United States)

    Richard, Jocelyn M; Castro, Daniel C; Difeliceantonio, Alexandra G; Robinson, Mike J F; Berridge, Kent C

    2013-11-01

    Ann Kelley was a scientific pioneer in reward neuroscience. Her many notable discoveries included demonstrations of accumbens/striatal circuitry roles in eating behavior and in food reward, explorations of limbic interactions with hypothalamic regulatory circuits, and additional interactions of motivation circuits with learning functions. Ann Kelley's accomplishments inspired other researchers to follow in her footsteps, including our own laboratory group. Here we describe results from several lines of our research that sprang in part from earlier findings by Kelley and colleagues. We describe hedonic hotspots for generating intense pleasure 'liking', separate identities of 'wanting' versus 'liking' systems, a novel role for dorsal neostriatum in generating motivation to eat, a limbic keyboard mechanism in nucleus accumbens for generating intense desire versus intense dread, and dynamic limbic transformations of learned memories into motivation. We describe how origins for each of these themes can be traced to fundamental contributions by Ann Kelley. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Altered neural reward and loss processing and prediction error signalling in depression

    Science.gov (United States)

    Ubl, Bettina; Kuehner, Christine; Kirsch, Peter; Ruttorf, Michaela

    2015-01-01

    Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression. PMID:25567763

  1. Rare neural correlations implement robotic conditioning with delayed rewards and disturbances

    Directory of Open Access Journals (Sweden)

    Andrea eSoltoggio

    2013-04-01

    Full Text Available Neural conditioning associates cues and actions with following rewards. The environments in which robots operate, however, are pervaded by a variety of disturbing stimuli and uncertain timing. In particular, variable reward delays make it difficult to reconstruct which previous actions are responsible for following rewards. Such an uncertainty is handled by biological neural networks, but represents a challenge for computational models, suggesting the lack of a satisfactory theory for robotic neural conditioning. The present study demonstrates the use of rare neural correlations in making correct associations between rewards and previous cues or actions. Rare correlations are functional in selecting sparse synapses to be eligible for later weight updates if a reward occurs. The repetition of this process singles out the associating and reward-triggering pathways, and thereby copes with distal rewards. The neural network displays macro-level classical and operant conditioning, which is demonstrated in an interactive real-life human-robot interaction. The proposed mechanism models realistic conditioning in humans and animals and implements similar behaviours in neuro-robotic platforms.

  2. Neural mechanisms of reward processing associated with depression-related personality traits.

    Science.gov (United States)

    Umemoto, Akina; Holroyd, Clay B

    2017-07-01

    Although impaired reward processing in depression has been well-documented, the exact nature of that deficit remains poorly understood. To investigate the link between depression and the neural mechanisms of reward processing, we examined individual differences in personality. We recorded the electroencephalogram from healthy college students engaged in a probabilistic reinforcement learning task. Participants also completed several personality questionnaires that assessed traits related to reward sensitivity, motivation, and depression. We examined whether behavioral measures of reward learning and event-related potential components related to outcome processing and reward anticipation-namely, the cue and feedback-related reward positivity (RewP) and the stimulus preceding negativity (SPN)-would link these personality traits to depression. Participants who scored high in reward sensitivity produced a relatively larger feedback-RewP. By contrast, participants who scored high in depression learned the contingencies for infrequently rewarded cue-response combinations relatively poorly, exhibited a larger SPN, and produced a smaller feedback-RewP, especially to outcomes following cue-response combinations that were frequently rewarded. These results point to a primary deficit in reward valuation in individuals who score high in depression, with secondary consequences that impact reward learning and anticipation. Despite recent evidence arguing for an anticipatory deficit in depression, impaired reward valuation as a primary deficit should be further examined in clinical samples. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  3. Neural control of energy balance: translating circuits to therapies.

    Science.gov (United States)

    Gautron, Laurent; Elmquist, Joel K; Williams, Kevin W

    2015-03-26

    Recent insights into the neural circuits controlling energy balance and glucose homeostasis have rekindled the hope for development of novel treatments for obesity and diabetes. However, many therapies contribute relatively modest beneficial gains with accompanying side effects, and the mechanisms of action for other interventions remain undefined. This Review summarizes current knowledge linking the neural circuits regulating energy and glucose balance with current and potential pharmacotherapeutic and surgical interventions for the treatment of obesity and diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. 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.

  5. NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY RESPONSE IN ANXIETY AND DEPRESSION.

    Science.gov (United States)

    Burkhouse, Katie L; Kujawa, Autumn; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Phan, K Luan; Klumpp, Heide

    2016-04-01

    Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. The majority of the sample (68%; 35 out of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward-processing deficits prior to treatment. © 2016 Wiley Periodicals, Inc.

  6. Social Reward in Youth at Risk for Depression: A Preliminary Investigation of Subjective and Neural Differences.

    Science.gov (United States)

    Olino, Thomas M; Silk, Jennifer S; Osterritter, Catherine; Forbes, Erika E

    2015-11-01

    Offspring of depressed parents are at risk for developing depression at rates higher than the general population. One potential mechanism linking parent and offspring depression involves attenuated reward function. Despite the importance of social incentives for adolescents, no previous studies have relied on active social incentive reward paradigms in youth at risk for depression. The present study examined differences in youth self- and parent-report measures of and neural response to social reward between youth of mothers with and those of mothers without a history of depression. Imaging data were collected on 10 youth with a depressed parent and 23 youth without depressed parent, which included a task examining neural response to social rewards. Youth and parents also completed self-report measures of social reward. Offspring of depressed parents had lower levels of parent-reported affiliation and reduced neural response to social reward in the ventral striatum and anterior cingulate cortex than offspring of parents without a history of depression. Higher parent-reported affiliation was associated with greater ventral striatal response to social reward. Data suggest that risk status differences in ventral striatal response to social acceptance may be accounted for by affiliation. No differences were found in youth self-reports of behavior. The results suggest that attenuated response to social reward, assessed through neurobiology and behavior, may be mechanistically linked to the etiology and pathophysiology of depression. Targeting social interest and engagement may be a new direction in preventing the onset of depressive disorders in youth.

  7. Relief as a reward: hedonic and neural responses to safety from pain.

    Directory of Open Access Journals (Sweden)

    Siri Leknes

    2011-04-01

    Full Text Available Relief fits the definition of a reward. Unlike other reward types the pleasantness of relief depends on the violation of a negative expectation, yet this has not been investigated using neuroimaging approaches. We hypothesized that the degree of negative expectation depends on state (dread and trait (pessimism sensitivity. Of the brain regions that are involved in mediating pleasure, the nucleus accumbens also signals unexpected reward and positive prediction error. We hypothesized that accumbens activity reflects the level of negative expectation and subsequent pleasant relief. Using fMRI and two purpose-made tasks, we compared hedonic and BOLD responses to relief with responses during an appetitive reward task in 18 healthy volunteers. We expected some similarities in task responses, reflecting common neural substrates implicated across reward types. However, we also hypothesized that relief responses would differ from appetitive rewards in the nucleus accumbens, since only relief pleasantness depends on negative expectations. The results confirmed these hypotheses. Relief and appetitive reward task activity converged in the ventromedial prefrontal cortex, which also correlated with appetitive reward pleasantness ratings. In contrast, dread and pessimism scores correlated with relief but not with appetitive reward hedonics. Moreover, only relief pleasantness covaried with accumbens activation. Importantly, the accumbens signal appeared to specifically reflect individual differences in anticipation of the adverse event (dread, pessimism but was uncorrelated to appetitive reward hedonics. In conclusion, relief differs from appetitive rewards due to its reliance on negative expectations, the violation of which is reflected in relief-related accumbens activation.

  8. Adolescents' Reward-related Neural Activation: Links to Thoughts of Nonsuicidal Self-Injury.

    Science.gov (United States)

    Poon, Jennifer A; Thompson, James C; Forbes, Erika E; Chaplin, Tara M

    2018-01-19

    Adolescence is a critical developmental period marked by an increase in risk behaviors, including nonsuicidal self-injury (NSSI). Heightened reward-related brain activation and relatively limited recruitment of prefrontal regions contribute to the initiation of risky behaviors in adolescence. However, neural reward processing has not been examined among adolescents who are at risk for future engagement for NSSI specifically, but who have yet to actually engage in this behavior. In the current fMRI study (N = 71), we hypothesized that altered reward processing would be associated with adolescents' thoughts of NSSI. Results showed that NSSI youth exhibited heightened activation in the bilateral putamen in response to a monetary reward. This pattern of findings suggests that heightened neural sensitivity to reward is associated with thoughts of NSSI in early adolescence. Implications for prevention are discussed. © 2018 The American Association of Suicidology.

  9. Neural responses during the anticipation and receipt of olfactory reward and punishment in human

    DEFF Research Database (Denmark)

    Zou, Lai-Quan; Zhou, Han-Yu; Zhuang, Yuan

    2018-01-01

    Pleasure experience is an important part of normal healthy life and is essential for general and mental well-being. Many neuroimaging studies have investigated the underlying neural processing of verbal and visual modalities of reward. However, how the brain processes rewards in the olfactory...... modality is not fully understood. This study aimed to examine the neural basis of olfactory rewards in 25 healthy participants using functional magnetic resonance imaging (fMRI). We developed an Olfactory Incentive Delay (OLID) imaging task distinguishing between the anticipation and receipt of olfactory...... rewards and punishments. We found that the pallidum was activated during the anticipation of both olfactory rewards and punishments. The bilateral insula was activated independently from the odours' hedonic valence during the receipt phase. In addition, right caudate activation during the anticipation...

  10. Amygdala neural activity reflects spatial attention towards stimuli promising reward or threatening punishment.

    Science.gov (United States)

    Peck, Christopher J; Salzman, C Daniel

    2014-10-30

    Humans and other animals routinely identify and attend to sensory stimuli so as to rapidly acquire rewards or avoid aversive experiences. Emotional arousal, a process mediated by the amygdala, can enhance attention to stimuli in a non-spatial manner. However, amygdala neural activity was recently shown to encode spatial information about reward-predictive stimuli, and to correlate with spatial attention allocation. If representing the motivational significance of sensory stimuli within a spatial framework reflects a general principle of amygdala function, then spatially selective neural responses should also be elicited by sensory stimuli threatening aversive events. Recordings from amygdala neurons were therefore obtained while monkeys directed spatial attention towards stimuli promising reward or threatening punishment. Neural responses encoded spatial information similarly for stimuli associated with both valences of reinforcement, and responses reflected spatial attention allocation. The amygdala therefore may act to enhance spatial attention to sensory stimuli associated with rewarding or aversive experiences.

  11. Genetic control of active neural circuits

    Directory of Open Access Journals (Sweden)

    Leon Reijmers

    2009-12-01

    Full Text Available The use of molecular tools to study the neurobiology of complex behaviors has been hampered by an inability to target the desired changes to relevant groups of neurons. Specific memories and specific sensory representations are sparsely encoded by a small fraction of neurons embedded in a sea of morphologically and functionally similar cells. In this review we discuss genetics techniques that are being developed to address this difficulty. In several studies the use of promoter elements that are responsive to neural activity have been used to drive long lasting genetic alterations into neural ensembles that are activated by natural environmental stimuli. This approach has been used to examine neural activity patterns during learning and retrieval of a memory, to examine the regulation of receptor trafficking following learning and to functionally manipulate a specific memory trace. We suggest that these techniques will provide a general approach to experimentally investigate the link between patterns of environmentally activated neural firing and cognitive processes such as perception and memory.

  12. Adaptive Neurotechnology for Making Neural Circuits Functional .

    Science.gov (United States)

    Jung, Ranu

    2008-03-01

    Two of the most important trends in recent technological developments are that technology is increasingly integrated with biological systems and that it is increasingly adaptive in its capabilities. Neuroprosthetic systems that provide lost sensorimotor function after a neural disability offer a platform to investigate this interplay between biological and engineered systems. Adaptive neurotechnology (hardware and software) could be designed to be biomimetic, guided by the physical and programmatic constraints observed in biological systems, and allow for real-time learning, stability, and error correction. An example will present biomimetic neural-network hardware that can be interfaced with the isolated spinal cord of a lower vertebrate to allow phase-locked real-time neural control. Another will present adaptive neural network control algorithms for functional electrical stimulation of the peripheral nervous system to provide desired movements of paralyzed limbs in rodents or people. Ultimately, the frontier lies in being able to utilize the adaptive neurotechnology to promote neuroplasticity in the living system on a long-time scale under co-adaptive conditions.

  13. Integrated Circuit For Simulation Of Neural Network

    Science.gov (United States)

    Thakoor, Anilkumar P.; Moopenn, Alexander W.; Khanna, Satish K.

    1988-01-01

    Ballast resistors deposited on top of circuit structure. Cascadable, programmable binary connection matrix fabricated in VLSI form as basic building block for assembly of like units into content-addressable electronic memory matrices operating somewhat like networks of neurons. Connections formed during storage of data, and data recalled from memory by prompting matrix with approximate or partly erroneous signals. Redundancy in pattern of connections causes matrix to respond with correct stored data.

  14. Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa.

    Science.gov (United States)

    Cowdrey, Felicity A; Park, Rebecca J; Harmer, Catherine J; McCabe, Ciara

    2011-10-15

    Recent evidence has shown that individuals with acute anorexia nervosa and those recovered have aberrant physiological responses to rewarding stimuli. We hypothesized that women recovered from anorexia nervosa would show aberrant neural responses to both rewarding and aversive disorder-relevant stimuli. Using functional magnetic resonance imaging (fMRI), the neural response to the sight and flavor of chocolate, and their combination, in 15 women recovered from restricting-type anorexia nervosa and 16 healthy control subjects matched for age and body mass index was investigated. The neural response to a control aversive condition, consisting of the sight of moldy strawberries and a corresponding unpleasant taste, was also measured. Participants simultaneously recorded subjective ratings of "pleasantness," "intensity," and "wanting." Despite no differences between the groups in subjective ratings, individuals recovered from anorexia nervosa showed increased neural response to the pleasant chocolate taste in the ventral striatum and pleasant chocolate sight in the occipital cortex. The recovered participants also showed increased neural response to the aversive strawberry taste in the insula and putamen and to the aversive strawberry sight in the anterior cingulate cortex and caudate. Individuals recovered from anorexia nervosa have increased neural responses to both rewarding and aversive food stimuli. These findings suggest that even after recovery, women with anorexia nervosa have increased salience attribution to food stimuli. These results aid our neurobiological understanding and support the view that the neural response to reward may constitute a neural biomarker for anorexia nervosa. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  15. Classical Conditioning with Pulsed Integrated Neural Networks: Circuits and System

    DEFF Research Database (Denmark)

    Lehmann, Torsten

    1998-01-01

    In this paper we investigate on-chip learning for pulsed, integrated neural networks. We discuss the implementational problems the technology imposes on learning systems and we find that abiologically inspired approach using simple circuit structures is most likely to bring success. We develop a ...... chip to solve simple classical conditioning tasks, thus verifying the design methodologies put forward in the paper....

  16. Railway Track Circuit Fault Diagnosis Using Recurrent Neural Networks

    NARCIS (Netherlands)

    de Bruin, T.D.; Verbert, K.A.J.; Babuska, R.

    2017-01-01

    Timely detection and identification of faults in railway track circuits are crucial for the safety and availability of railway networks. In this paper, the use of the long-short-term memory (LSTM) recurrent neural network is proposed to accomplish these tasks based on the commonly available

  17. Railway track circuit fault diagnosis using recurrent neural networks

    NARCIS (Netherlands)

    de Bruin, T.D.; Verbert, K.A.J.; Babuska, R.

    2017-01-01

    Timely detection and identification of faults in railway track circuits are crucial for the safety and availability of railway networks. In this paper, the use of the long-short-term memory (LSTM) recurrent neural network is proposed to accomplish these tasks based on the commonly available

  18. Distinct neural circuits subserve interpersonal and non-interpersonal emotions.

    Science.gov (United States)

    Landa, Alla; Wang, Zhishun; Russell, James A; Posner, Jonathan; Duan, Yunsuo; Kangarlu, Alayar; Huo, Yuankai; Fallon, Brian A; Peterson, Bradley S

    2013-01-01

    Emotions elicited by interpersonal versus non-interpersonal experiences have different effects on neurobiological functioning in both animals and humans. However, the extent to which the brain circuits underlying interpersonal and non-interpersonal emotions are distinct still remains unclear. The goal of our study was to assess whether different neural circuits are implicated in the processing of arousal and valence of interpersonal versus non-interpersonal emotions. During functional magnetic resonance imaging, participants imagined themselves in emotion-eliciting interpersonal or non-interpersonal situations and then rated the arousal and valence of emotions they experienced. We identified (1) separate neural circuits that are implicated in the arousal and valence dimensions of interpersonal versus non-interpersonal emotions, (2) circuits that are implicated in arousal and valence for both types of emotion, and (3) circuits that are responsive to the type of emotion, regardless of the valence or arousal level of the emotion. We found extensive recruitment of limbic (for arousal) and temporal-parietal (for valence) systems associated with processing of specifically interpersonal emotions compared to non-interpersonal ones. The neural bases of interpersonal and non-interpersonal emotions may, therefore, be largely distinct.

  19. Distinct Neural Circuits Subserve Interpersonal and Non-interpersonal Emotions

    Science.gov (United States)

    Landa, Alla; Wang, Zhishun; Russell, James A.; Posner, Jonathan; Duan, Yunsuo; Kangarlu, Alayar; Huo, Yuankai; Fallon, Brian A.; Peterson, Bradley S.

    2013-01-01

    Emotions elicited by interpersonal versus non-interpersonal experiences have different effects on neurobiological functioning in both animals and humans. However, the extent to which the brain circuits underlying interpersonal and non-interpersonal emotions are distinct still remains unclear. The goal of our study was to assess whether different neural circuits are implicated in the processing of arousal and valence of interpersonal versus non-interpersonal emotions. During functional magnetic resonance imaging, participants imagined themselves in emotion-eliciting interpersonal or non-interpersonal situations and then rated the arousal and valence of emotions they experienced. We identified (a) separate neural circuits that are implicated in the arousal and valence dimensions of interpersonal versus non-interpersonal emotions, (b) circuits that are implicated in arousal and valence for both types of emotion, and (c) circuits that are responsive to the type of emotion, regardless of the valence or arousal level of the emotion. We found extensive recruitment of limbic (for arousal) and temporal-parietal (for valence) systems associated with processing of specifically interpersonal emotions compared to non-interpersonal ones. The neural bases of interpersonal and non-interpersonal emotions may, therefore, be largely distinct. PMID:24028312

  20. Neural Correlates of Reward Processing in Typical and Atypical Development

    Directory of Open Access Journals (Sweden)

    Emma G. Duerden PhD

    2016-09-01

    Full Text Available Atypically developing children including those born preterm or who have autism spectrum disorder can display difficulties with evaluating rewarding stimuli, which may result from impaired maturation of reward and cognitive control brain regions. During functional magnetic resonance imaging, 58 typically and atypically developing children (6-12 years participated in a set-shifting task that included the presentation of monetary reward stimuli. In typically developing children, reward stimuli were associated with age-related increases in activation in cognitive control centers, with weaker changes in reward regions. In atypically developing children, no age-related changes were evident. Maturational disturbances in the frontostriatal regions during atypical development may underlie task-based differences in activation.

  1. Hox genes: choreographers in neural development, architects of circuit organization.

    Science.gov (United States)

    Philippidou, Polyxeni; Dasen, Jeremy S

    2013-10-02

    The neural circuits governing vital behaviors, such as respiration and locomotion, are comprised of discrete neuronal populations residing within the brainstem and spinal cord. Work over the past decade has provided a fairly comprehensive understanding of the developmental pathways that determine the identity of major neuronal classes within the neural tube. However, the steps through which neurons acquire the subtype diversities necessary for their incorporation into a particular circuit are still poorly defined. Studies on the specification of motor neurons indicate that the large family of Hox transcription factors has a key role in generating the subtypes required for selective muscle innervation. There is also emerging evidence that Hox genes function in multiple neuronal classes to shape synaptic specificity during development, suggesting a broader role in circuit assembly. This Review highlights the functions and mechanisms of Hox gene networks and their multifaceted roles during neuronal specification and connectivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Neuronify: An Educational Simulator for Neural Circuits.

    Science.gov (United States)

    Dragly, Svenn-Arne; Hobbi Mobarhan, Milad; Våvang Solbrå, Andreas; Tennøe, Simen; Hafreager, Anders; Malthe-Sørenssen, Anders; Fyhn, Marianne; Hafting, Torkel; Einevoll, Gaute T

    2017-01-01

    Educational software (apps) can improve science education by providing an interactive way of learning about complicated topics that are hard to explain with text and static illustrations. However, few educational apps are available for simulation of neural networks. Here, we describe an educational app, Neuronify, allowing the user to easily create and explore neural networks in a plug-and-play simulation environment. The user can pick network elements with adjustable parameters from a menu, i.e., synaptically connected neurons modelled as integrate-and-fire neurons and various stimulators (current sources, spike generators, visual, and touch) and recording devices (voltmeter, spike detector, and loudspeaker). We aim to provide a low entry point to simulation-based neuroscience by allowing students with no programming experience to create and simulate neural networks. To facilitate the use of Neuronify in teaching, a set of premade common network motifs is provided, performing functions such as input summation, gain control by inhibition, and detection of direction of stimulus movement. Neuronify is developed in C++ and QML using the cross-platform application framework Qt and runs on smart phones (Android, iOS) and tablet computers as well personal computers (Windows, Mac, Linux).

  3. Girls’ Challenging Social Experiences in Early Adolescence Predict Neural Response to Rewards and Depressive Symptoms1

    Science.gov (United States)

    Casement, Melynda D.; Guyer, Amanda E.; Hipwell, Alison; McAloon, Rose L.; Hoffmann, Amy M.; Keenan, Kathryn; Forbes, Erika E.

    2014-01-01

    Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. PMID:24397999

  4. Girls' challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms.

    Science.gov (United States)

    Casement, Melynda D; Guyer, Amanda E; Hipwell, Alison E; McAloon, Rose L; Hoffmann, Amy M; Keenan, Kathryn E; Forbes, Erika E

    2014-04-01

    Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Girls’ challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms

    Directory of Open Access Journals (Sweden)

    Melynda D. Casement

    2014-04-01

    Full Text Available Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC, striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence.

  6. Influences of social reward experience on behavioral responses to drugs of abuse: Review of shared and divergent neural plasticity mechanisms for sexual reward and drugs of abuse.

    Science.gov (United States)

    Beloate, Lauren N; Coolen, Lique M

    2017-12-01

    Different factors influence the development of drug addiction in humans, including social reward experiences. In animals, experience with social rewards, such as sexual behavior, pair bonding, social and environmental enrichment, can be protective. However, loss or lack of social rewards can lead to a vulnerability to drug-seeking behavior. The effects of social reward experience on drug-seeking behavior are associated with changes in the neural pathways that control drug-related behavior. This review will provide an introduction and overview of the mesolimbic pathway and the influence of social reward experience on drug-seeking behavior in rodents. Moreover, the research from our laboratory on effects of sexual experience and loss of sex reward on psychostimulant and opiate reward will be reviewed. Finally, we will review current knowledge of the neural mechanisms that underlie these interactions. Investigations of the neural underpinnings by which social and drug rewards interact contribute to improved understanding of the neural basis of vulnerability for drug addiction and reward-related behaviors in general. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. At what stage of neural processing does cocaine act to boost pursuit of rewards?

    Directory of Open Access Journals (Sweden)

    Giovanni Hernandez

    2010-11-01

    Full Text Available Dopamine-containing neurons have been implicated in reward and decision making. One element of the supporting evidence is that cocaine, like other drugs that increase dopaminergic neurotransmission, powerfully potentiates reward seeking. We analyze this phenomenon from a novel perspective, introducing a new conceptual framework and new methodology for determining the stage(s of neural processing at which drugs, lesions and physiological manipulations act to influence reward-seeking behavior. Cocaine strongly boosts the proclivity of rats to work for rewarding electrical brain stimulation. We show that the conventional conceptual framework and methods do not distinguish between three conflicting accounts of how the drug produces this effect: increased sensitivity of brain reward circuitry, increased gain, or decreased subjective reward costs. Sensitivity determines the stimulation strength required to produce a reward of a given intensity (a measure analogous to the KM of an enzyme whereas gain determines the maximum intensity attainable (a measure analogous to the vmax of an enzyme-catalyzed reaction. To distinguish sensitivity changes from the other determinants, we measured and modeled reward seeking as a function of both stimulation strength and opportunity cost. The principal effect of cocaine was a two-fourfold increase in willingness to pay for the electrical reward, an effect consistent with increased gain or decreased subjective cost. This finding challenges the long-standing view that cocaine increases the sensitivity of brain reward circuitry. We discuss the implications of the results and the analytic approach for theories of how dopaminergic neurons and other diffuse modulatory brain systems contribute to reward pursuit, and we explore the implications of the conceptual framework for the study of natural rewards, drug reward, and mood.

  8. Localizing complex neural circuits with MEG data.

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    Belardinelli, P; Ciancetta, L; Pizzella, V; Del Gratta, C; Romani, G L

    2006-03-01

    During cognitive processing, the various cortical areas, with specialized functions, supply for different tasks. In most cases then, the information flows are processed in a parallel way by brain networks which work together integrating the single performances for a common goal. Such a step is generally performed at higher processing levels in the associative areas. The frequency range at which neuronal pools oscillate is generally wider than the one which is detectable by bold changes in fMRI studies. A high time resolution technique like magnetoencephalography or electroencephalography is therefore required as well as new data processing algorithms for detecting different coherent brain areas cooperating for one cognitive task. Our experiments show that no algorithm for the inverse problem solution is immune from bias. We propose therefore, as a possible solution, our software LOCANTO (LOcalization and Coherence ANalysis TOol). This new package features a set of tools for the detection of coherent areas. For such a task, as a default, it employs the algorithm with best performances for the neural landscape to be detected. If the neural landscape under attention involves more than two interacting areas the SLoreta algorithm is used. Our study shows in fact that SLoreta performance is not biased when the correlation among multiple sources is high. On the other hand, the Beamforming algorithm is more precise than SLoreta at localizing single or double sources but it gets a relevant localization bias when the sources are more than three and are highly correlated.

  9. Neural processing of reward and punishment in young people at increased familial risk of depression.

    Science.gov (United States)

    McCabe, Ciara; Woffindale, Caroline; Harmer, Catherine J; Cowen, Philip J

    2012-10-01

    Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16-21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Eveningness among late adolescent males predicts neural reactivity to reward and alcohol dependence 2 years later.

    Science.gov (United States)

    Hasler, Brant P; Casement, Melynda D; Sitnick, Stephanie L; Shaw, Daniel S; Forbes, Erika E

    2017-06-01

    Eveningness, a preference for later sleep-wake timing, is linked to altered reward function, which may explain a consistent association with substance abuse. Notably, the extant literature rests largely on cross-sectional data, yet both eveningness and reward function show developmental changes. We examined whether circadian preference during late adolescence predicted the neural response to reward 2 years later. A sample of 93 males reported circadian preference and completed a monetary reward fMRI paradigm at ages 20 and 22. Primary analyses examined longitudinal paths from circadian preference to medial prefrontal cortex (mPFC) and ventral striatal (VS) reward responses. We also explored whether reward responses mediated longitudinal associations between circadian preference and alcohol dependence, frequency of alcohol use, and/or frequency of cannabis use. Age 20 eveningness was positively associated with age 22 mPFC and VS responses to win, but not associated with age 22 reactivity to reward anticipation. Age 20 eveningness was indirectly related to age 22 alcohol dependence via age 22 mPFC response to win. Our findings provide novel evidence that altered reward-related brain function could underlie associations between eveningness and alcohol use problems. Eveningness may be an under-recognized but modifiable risk factor for reward-related problems such as mood and substance use disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Developmental plasticity in neural circuits for a learned behavior.

    Science.gov (United States)

    Bottjer, S W; Arnold, A P

    1997-01-01

    The neural substrate underlying learned vocal behavior in songbirds provides a textbook illustration of anatomical localization of function for a complex learned behavior in vertebrates. The song-control system has become an important model for studying neural systems related to learning, behavior, and development. The song system of zebra finches is characterized by a heightened capacity for both neural and behavioral change during development and has taught us valuable information regarding sensitive periods, rearrangement of synaptic connections, topographic specificity, cell death and neurogenesis, experience-dependent neural plasticity, and sexual differentiation. The song system differs in some interesting ways from some well-studied mammalian model systems and thus offers fresh perspectives on specific theoretical issues. In this highly selective review, we concentrate on two major questions: What are the developmental changes in the song system responsible for song learning and the restriction of learning to a sensitive period, and what factors explain the highly sexually dimorphic development of this system? We discuss the important role of sex steroid hormones and of neurotrophins in creating a male-typical neural song circuit (which can learn to produce complex vocalizations) instead of a reduced, female-typical song circuit that does not produce learned song.

  12. Neural mechanisms of individual differences in temporal discounting of monetary and primary rewards in adolescents.

    Science.gov (United States)

    de Water, Erik; Mies, Gabry W; Figner, Bernd; Yoncheva, Yuliya; van den Bos, Wouter; Castellanos, F Xavier; Cillessen, Antonius H N; Scheres, Anouk

    2017-06-01

    Adolescents are generally characterized as impulsive. However, impulsivity is a multi-dimensional construct that involves multiple component processes. Which of these components contribute to adolescent impulsivity is currently unclear. This study focused on the neural mechanisms underlying individual differences in distinct components of temporal discounting (TD), i.e., the preference for smaller immediate rewards over larger delayed rewards. Participants were 58 adolescents (12-16 years-old) who performed an fMRI TD task with both monetary and snack rewards. Using mixed-effects modeling, we determined participants' average impatience, and further decomposed TD choices into: 1) amount sensitivity (unique contribution of the magnitude of the immediate reward); and 2) delay sensitivity (unique contribution of delay duration). Adolescents' average impatience was positively correlated with frontoparietal and ventral striatal activity during delayed reward choices, and with ventromedial prefrontal cortex activity during immediate reward choices. Adolescents' amount sensitivity was positively associated with ventral striatal and dorsal anterior cingulate cortex activity during immediate reward choices. Delay sensitivity was positively correlated with inferior parietal cortex activity during delayed reward choices. As expected, snacks were discounted more steeply than money, and TD of both reward types was associated with overlapping activation in the inferior parietal cortex. Exploring whether testosterone or estradiol were associated with TD and its neural correlates revealed no significant associations. These findings indicate that distinct components contribute uniquely to TD choice and that individual differences in amount sensitivity are uniquely associated with activation of reward valuation areas, while individual differences in delay sensitivity are uniquely associated with activation of cognitive control areas. Copyright © 2017 Elsevier Inc. All rights

  13. Synchrony and neural coding in cerebellar circuits

    Directory of Open Access Journals (Sweden)

    Abigail L Person

    2012-12-01

    circuits.

  14. Functional neural circuits that underlie developmental stuttering.

    Directory of Open Access Journals (Sweden)

    Jianping Qiao

    Full Text Available The aim of this study was to identify differences in functional and effective brain connectivity between persons who stutter (PWS and typically developing (TD fluent speakers, and to assess whether those differences can serve as biomarkers to distinguish PWS from TD controls. We acquired resting-state functional magnetic resonance imaging data in 44 PWS and 50 TD controls. We then used Independent Component Analysis (ICA together with Hierarchical Partner Matching (HPM to identify networks of robust, functionally connected brain regions that were highly reproducible across participants, and we assessed whether connectivity differed significantly across diagnostic groups. We then used Granger Causality (GC to study the causal interactions (effective connectivity between the regions that ICA and HPM identified. Finally, we used a kernel support vector machine to assess how well these measures of functional connectivity and granger causality discriminate PWS from TD controls. Functional connectivity was stronger in PWS compared with TD controls in the supplementary motor area (SMA and primary motor cortices, but weaker in inferior frontal cortex (IFG, Broca's area, caudate, putamen, and thalamus. Additionally, causal influences were significantly weaker in PWS from the IFG to SMA, and from the basal ganglia to IFG through the thalamus, compared to TD controls. ICA and GC indices together yielded an accuracy of 92.7% in classifying PWS from TD controls. Our findings suggest the presence of dysfunctional circuits that support speech planning and timing cues for the initiation and execution of motor sequences in PWS. Our high accuracy of classification further suggests that these aberrant brain features may serve as robust biomarkers for PWS.

  15. Functional neural circuits that underlie developmental stuttering

    Science.gov (United States)

    Zhao, Guihu; Huo, Yuankai; Herder, Carl L.; Sikora, Chamonix O.; Peterson, Bradley S.

    2017-01-01

    The aim of this study was to identify differences in functional and effective brain connectivity between persons who stutter (PWS) and typically developing (TD) fluent speakers, and to assess whether those differences can serve as biomarkers to distinguish PWS from TD controls. We acquired resting-state functional magnetic resonance imaging data in 44 PWS and 50 TD controls. We then used Independent Component Analysis (ICA) together with Hierarchical Partner Matching (HPM) to identify networks of robust, functionally connected brain regions that were highly reproducible across participants, and we assessed whether connectivity differed significantly across diagnostic groups. We then used Granger Causality (GC) to study the causal interactions (effective connectivity) between the regions that ICA and HPM identified. Finally, we used a kernel support vector machine to assess how well these measures of functional connectivity and granger causality discriminate PWS from TD controls. Functional connectivity was stronger in PWS compared with TD controls in the supplementary motor area (SMA) and primary motor cortices, but weaker in inferior frontal cortex (IFG, Broca’s area), caudate, putamen, and thalamus. Additionally, causal influences were significantly weaker in PWS from the IFG to SMA, and from the basal ganglia to IFG through the thalamus, compared to TD controls. ICA and GC indices together yielded an accuracy of 92.7% in classifying PWS from TD controls. Our findings suggest the presence of dysfunctional circuits that support speech planning and timing cues for the initiation and execution of motor sequences in PWS. Our high accuracy of classification further suggests that these aberrant brain features may serve as robust biomarkers for PWS. PMID:28759567

  16. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function.

    Science.gov (United States)

    Subramaniam, Karuna; Hooker, Christine I; Biagianti, Bruno; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

    2015-01-01

    Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal-striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal-striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life.

  17. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

    Directory of Open Access Journals (Sweden)

    Karuna Subramaniam

    2015-01-01

    Full Text Available Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC participants, reward anticipation is associated with activity in frontal–striatal networks. By contrast, schizophrenia (SZ participants show hypoactivation within these frontal–striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life.

  18. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

    Science.gov (United States)

    Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2017-02-01

    Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

  19. Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

    Science.gov (United States)

    Subramaniam, Karuna; Hooker, Christine I.; Biagianti, Bruno; Fisher, Melissa; Nagarajan, Srikantan; Vinogradov, Sophia

    2015-01-01

    Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal–striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal–striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life. PMID:26413478

  20. Neural representation of reward probability: evidence from the illusion of control.

    Science.gov (United States)

    Kool, Wouter; Getz, Sarah J; Botvinick, Matthew M

    2013-06-01

    To support reward-based decision-making, the brain must encode potential outcomes both in terms of their incentive value and their probability of occurrence. Recent research has made it clear that the brain bears multiple representations of reward magnitude, meaning that a single choice option may be represented differently-and even inconsistently-in different brain areas. There are some hints that the same may be true for reward probability. Preliminary evidence hints that, even as systematic distortions of probability are expressed in behavior, these may not always be uniformly reflected at the neural level: Some neural representations of probability may be immune from such distortions. This study provides new evidence consistent with this possibility. Participants in a behavioral experiment displayed a classic "illusion of control," providing higher estimates of reward probability for gambles they had chosen than for identical gambles that were imposed on them. However, an fMRI study of the same task revealed that neural prediction error signals, arising when gamble outcomes were revealed, were unaffected by the illusion of control. The resulting behavioral-neural dissociation reinforces the case for multiple, inconsistent internal representations of reward probability, while also prompting a reinterpretation of the illusion of control effect itself.

  1. Breathtaking Songs: Coordinating the Neural Circuits for Breathing and Singing.

    Science.gov (United States)

    Schmidt, Marc F; Goller, Franz

    2016-11-01

    The vocal behavior of birds is remarkable for its diversity, and songs can feature elaborate characteristics such as long duration, rapid temporal pattern, and broad frequency range. The respiratory system plays a central role in generating the complex song patterns that must be integrated with its life-sustaining functions. Here, we explore how precise coordination between the neural circuits for breathing and singing is fundamental to production of these remarkable behaviors. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

  2. Oxytocin modulation of neural circuits for social behavior.

    Science.gov (United States)

    Marlin, Bianca J; Froemke, Robert C

    2017-02-01

    Oxytocin is a hypothalamic neuropeptide that has gained attention for the effects on social behavior. Recent findings shed new light on the mechanisms of oxytocin in synaptic plasticity and adaptively modifying neural circuits for social interactions such as conspecific recognition, pair bonding, and maternal care. Here, we review several of these newer studies on oxytocin in the context of previous findings, with an emphasis on social behavior and circuit plasticity in various brain regions shown to be enriched for oxytocin receptors. We provide a framework that highlights current circuit-level mechanisms underlying the widespread action of oxytocin. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 169-189, 2017. © 2016 Wiley Periodicals, Inc.

  3. Neural reactivity to reward in school-age offspring of depressed mothers.

    Science.gov (United States)

    Wiggins, Jillian Lee; Schwartz, Karen T G; Kryza-Lacombe, Maria; Spechler, Philip A; Blankenship, Sarah L; Dougherty, Lea R

    2017-05-01

    Identifying neural profiles predictive of future psychopathology in at-risk individuals is important to efficiently direct preventive care. Alterations in reward processing may be a risk factor for depression. The current study characterized neural substrates of reward processing in children at low- and high-risk for psychopathology due to maternal depression status. Children with (n=27) and without (n=19) maternal depression (ages 5.9-9.6 years) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during fMRI acquisition. Multiple dorsal prefrontal, temporal, and striatal regions showed significant Group (high- vs. low-risk)×Performance (hit vs. miss)×Condition (no reward vs. reward) interactions in a whole-brain analysis. All regions exhibited similar patterns, whereby the high-risk group showed blunted activation differences between trials with vs. without rewards when participants hit the target. Moreover, high-risk children showed activation differences between trials with vs. without rewards in the opposite direction, compared to the low-risk group, when they missed the target. This study had a modest sample size, though larger than existing studies. Children with maternal depression are at elevated risk for future psychopathology, yet not all experience clinically significant symptoms; longitudinal research is necessary to fully track the pathway from risk to disorder. Children of depressed mothers exhibited attenuated neural activation differences and activation patterns opposite to children without depressed mothers. Our findings may provide targets for hypothesis-driven preventive interventions and lead to earlier identification of individuals at risk. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Trait Rumination Influences Neural Correlates of the Anticipation but Not the Consumption Phase of Reward Processing

    Directory of Open Access Journals (Sweden)

    Natália Kocsel

    2017-05-01

    Full Text Available Cumulative evidence suggests that trait rumination can be defined as an abstract information processing mode, which leads people to constantly anticipate the likely impact of present events on future events and experiences. A previous study with remitted depressed patients suggested that enhanced rumination tendencies distort brain mechanisms of anticipatory processes associated with reward and loss cues. In the present study, we explored the impact of trait rumination on neural activity during reward and loss anticipation among never-depressed people. We analyzed the data of 37 healthy controls, who performed the monetary incentive delay (MID task which was designed for the simultaneous measurement of the anticipation (motivational and consumption (hedonic phase of reward processing, during functional magnetic resonance imaging (fMRI. Our results show that rumination—after controlling for age, gender, and current mood—significantly influenced neural responses to reward (win cues compared to loss cues. Blood-oxygenation-level-dependent (BOLD activity in the left inferior frontal gyrus (IFG triangularis, left anterior insula, and left rolandic operculum was positively related to Ruminative Response Scale (RRS scores. We did not detect any significant rumination-related activations associated with win-neutral or loss-neutral cues and with reward or loss consumption. Our results highlight the influence of trait rumination on reward anticipation in a non-depressed sample. They also suggest that for never-depressed ruminators rewarding cues are more salient than loss cues. BOLD response during reward consumption did not relate to rumination, suggesting that rumination mainly relates to processing of the motivational (wanting aspect of reward rather than the hedonic (liking aspect, at least in the absence of pathological mood.

  5. KCNQ potassium channels in sensory system and neural circuits.

    Science.gov (United States)

    Wang, Jing-jing; Li, Yang

    2016-01-01

    M channels, an important regulator of neural excitability, are composed of four subunits of the Kv7 (KCNQ) K(+) channel family. M channels were named as such because their activity was suppressed by stimulation of muscarinic acetylcholine receptors. These channels are of particular interest because they are activated at the subthreshold membrane potentials. Furthermore, neural KCNQ channels are drug targets for the treatments of epilepsy and a variety of neurological disorders, including chronic and neuropathic pain, deafness, and mental illness. This review will update readers on the roles of KCNQ channels in the sensory system and neural circuits as well as discuss their respective mechanisms and the implications for physiology and medicine. We will also consider future perspectives and the development of additional pharmacological models, such as seizure, stroke, pain and mental illness, which work in combination with drug-design targeting of KCNQ channels. These models will hopefully deepen our understanding of KCNQ channels and provide general therapeutic prospects of related channelopathies.

  6. Enhanced neural response to anticipation, effort and consummation of reward and aversion during bupropion treatment.

    Science.gov (United States)

    Dean, Z; Horndasch, S; Giannopoulos, P; McCabe, C

    2016-08-01

    We have previously shown that the selective serotonergic reuptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear. Seventeen healthy volunteers (9 female, 8 male) received 7 days bupropion (150 mg/day) and 7 days placebo treatment, in a double-blind crossover design. Our functional magnetic resonance imaging task consisted of three phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes. Relative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase. Our results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect.

  7. Is avoiding an aversive outcome rewarding? Neural substrates of avoidance learning in the human brain.

    Directory of Open Access Journals (Sweden)

    Hackjin Kim

    2006-07-01

    Full Text Available Avoidance learning poses a challenge for reinforcement-based theories of instrumental conditioning, because once an aversive outcome is successfully avoided an individual may no longer experience extrinsic reinforcement for their behavior. One possible account for this is to propose that avoiding an aversive outcome is in itself a reward, and thus avoidance behavior is positively reinforced on each trial when the aversive outcome is successfully avoided. In the present study we aimed to test this possibility by determining whether avoidance of an aversive outcome recruits the same neural circuitry as that elicited by a reward itself. We scanned 16 human participants with functional MRI while they performed an instrumental choice task, in which on each trial they chose from one of two actions in order to either win money or else avoid losing money. Neural activity in a region previously implicated in encoding stimulus reward value, the medial orbitofrontal cortex, was found to increase, not only following receipt of reward, but also following successful avoidance of an aversive outcome. This neural signal may itself act as an intrinsic reward, thereby serving to reinforce actions during instrumental avoidance.

  8. Enhanced Neural Responses to Imagined Primary Rewards Predict Reduced Monetary Temporal Discounting.

    Science.gov (United States)

    Hakimi, Shabnam; Hare, Todd A

    2015-09-23

    The pervasive tendency to discount the value of future rewards varies considerably across individuals and has important implications for health and well-being. Here, we used fMRI with human participants to examine whether an individual's neural representation of an imagined primary reward predicts the degree to which the value of delayed monetary payments is discounted. Because future rewards can never be experienced at the time of choice, imagining or simulating the benefits of a future reward may play a critical role in decisions between alternatives with either immediate or delayed benefits. We found that enhanced ventromedial prefrontal cortex response during imagined primary reward receipt was correlated with reduced discounting in a separate monetary intertemporal choice task. Furthermore, activity in enhanced ventromedial prefrontal cortex during reward imagination predicted temporal discounting behavior both between- and within-individual decision makers with 62% and 73% mean balanced accuracy, respectively. These results suggest that the quality of reward imagination may impact the degree to which future outcomes are discounted. Significance statement: We report a novel test of the hypothesis that an important factor influencing the discount rate for future rewards is the quality with which they are imagined or estimated in the present. Previous work has shown that temporal discounting is linked to individual characteristics ranging from general intelligence to the propensity for addiction. We demonstrate that individual differences in a neurobiological measure of primary reward imagination are significantly correlated with discounting rates for future monetary payments. Moreover, our neurobiological measure of imagination can be used to accurately predict choice behavior both between and within individuals. These results suggest that improving reward imagination may be a useful therapeutic target for individuals whose high discount rates promote

  9. Led into temptation? Rewarding brand logos bias the neural encoding of incidental economic decisions.

    Directory of Open Access Journals (Sweden)

    Carsten Murawski

    Full Text Available Human decision-making is driven by subjective values assigned to alternative choice options. These valuations are based on reward cues. It is unknown, however, whether complex reward cues, such as brand logos, may bias the neural encoding of subjective value in unrelated decisions. In this functional magnetic resonance imaging (fMRI study, we subliminally presented brand logos preceding intertemporal choices. We demonstrated that priming biased participants' preferences towards more immediate rewards in the subsequent temporal discounting task. This was associated with modulations of the neural encoding of subjective values of choice options in a network of brain regions, including but not restricted to medial prefrontal cortex. Our findings demonstrate the general susceptibility of the human decision making system to apparently incidental contextual information. We conclude that the brain incorporates seemingly unrelated value information that modifies decision making outside the decision-maker's awareness.

  10. Led into temptation? Rewarding brand logos bias the neural encoding of incidental economic decisions.

    Science.gov (United States)

    Murawski, Carsten; Harris, Philip G; Bode, Stefan; Domínguez D, Juan F; Egan, Gary F

    2012-01-01

    Human decision-making is driven by subjective values assigned to alternative choice options. These valuations are based on reward cues. It is unknown, however, whether complex reward cues, such as brand logos, may bias the neural encoding of subjective value in unrelated decisions. In this functional magnetic resonance imaging (fMRI) study, we subliminally presented brand logos preceding intertemporal choices. We demonstrated that priming biased participants' preferences towards more immediate rewards in the subsequent temporal discounting task. This was associated with modulations of the neural encoding of subjective values of choice options in a network of brain regions, including but not restricted to medial prefrontal cortex. Our findings demonstrate the general susceptibility of the human decision making system to apparently incidental contextual information. We conclude that the brain incorporates seemingly unrelated value information that modifies decision making outside the decision-maker's awareness.

  11. Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats.

    Science.gov (United States)

    Alvandi, Mina Sadighi; Bourmpoula, Maria; Homberg, Judith R; Fathollahi, Yaghoub

    2017-11-01

    Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse. © 2017 Society for the Study of Addiction.

  12. Healthy Adolescents' Neural Response to Reward: Associations with Puberty, Positive Affect, and Depressive Symptoms

    Science.gov (United States)

    Forbes, Erika E.; Ryan, Neal D.; Phillips, Mary L.; Manuck, Stephen B.; Worthman, Carol M.; Moyles, Donna L.; Tarr, Jill A.; Sciarrillo, Samantha R.; Dahl, Ronald E.

    2010-01-01

    Objective: Changes in reward-related behavior are an important component of normal adolescent affective development. Understanding the neural underpinnings of these normative changes creates a foundation for investigating adolescence as a period of vulnerability to affective disorders, substance use disorders, and health problems. Studies of…

  13. 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.

  14. 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

  15. Neural Reward Processing Mediates the Relationship between Insomnia Symptoms and Depression in Adolescence.

    Science.gov (United States)

    Casement, Melynda D; Keenan, Kate E; Hipwell, Alison E; Guyer, Amanda E; Forbes, Erika E

    2016-02-01

    Emerging evidence suggests that insomnia may disrupt reward-related brain function-a potentially important factor in the development of depressive disorder. Adolescence may be a period during which such disruption is especially problematic given the rise in the incidence of insomnia and ongoing development of neural systems that support reward processing. The present study uses longitudinal data to test the hypothesis that disruption of neural reward processing is a mechanism by which insomnia symptoms-including nocturnal insomnia symptoms (NIS) and nonrestorative sleep (NRS)-contribute to depressive symptoms in adolescent girls. Participants were 123 adolescent girls and their caregivers from an ongoing longitudinal study of precursors to depression across adolescent development. NIS and NRS were assessed annually from ages 9 to 13 years. Girls completed a monetary reward task during a functional MRI scan at age 16 years. Depressive symptoms were assessed at ages 16 and 17 years. Multivariable regression tested the prospective associations between NIS and NRS, neural response during reward anticipation, and the mean number of depressive symptoms (omitting sleep problems). NRS, but not NIS, during early adolescence was positively associated with late adolescent dorsal medial prefrontal cortex (dmPFC) response to reward anticipation and depressive symptoms. DMPFC response mediated the relationship between early adolescent NRS and late adolescent depressive symptoms. These results suggest that NRS may contribute to depression by disrupting reward processing via altered activity in a region of prefrontal cortex involved in affective control. The results also support the mechanistic differentiation of NIS and NRS. © 2016 Associated Professional Sleep Societies, LLC.

  16. Controlling the elements: an optogenetic approach to understanding the neural circuits of fear.

    Science.gov (United States)

    Johansen, Joshua P; Wolff, Steffen B E; Lüthi, Andreas; LeDoux, Joseph E

    2012-06-15

    Neural circuits underlie our ability to interact in the world and to learn adaptively from experience. Understanding neural circuits and how circuit structure gives rise to neural firing patterns or computations is fundamental to our understanding of human experience and behavior. Fear conditioning is a powerful model system in which to study neural circuits and information processing and relate them to learning and behavior. Until recently, technological limitations have made it difficult to study the causal role of specific circuit elements during fear conditioning. However, newly developed optogenetic tools allow researchers to manipulate individual circuit components such as anatomically or molecularly defined cell populations, with high temporal precision. Applying these tools to the study of fear conditioning to control specific neural subpopulations in the fear circuit will facilitate a causal analysis of the role of these circuit elements in fear learning and memory. By combining this approach with in vivo electrophysiological recordings in awake, behaving animals, it will also be possible to determine the functional contribution of specific cell populations to neural processing in the fear circuit. As a result, the application of optogenetics to fear conditioning could shed light on how specific circuit elements contribute to neural coding and to fear learning and memory. Furthermore, this approach may reveal general rules for how circuit structure and neural coding within circuits gives rise to sensory experience and behavior. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Food and drug reward: overlapping circuits in human obesity and addiction

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-01

    Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects - partly mediated by dopamine increases in the limbic system - that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioral inhibition), stress reactivity and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that investigate the role of dopamine in drug addiction and in obesity and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.

  18. The Complexity of Dynamics in Small Neural Circuits.

    Directory of Open Access Journals (Sweden)

    Diego Fasoli

    2016-08-01

    Full Text Available Mean-field approximations are a powerful tool for studying large neural networks. However, they do not describe well the behavior of networks composed of a small number of neurons. In this case, major differences between the mean-field approximation and the real behavior of the network can arise. Yet, many interesting problems in neuroscience involve the study of mesoscopic networks composed of a few tens of neurons. Nonetheless, mathematical methods that correctly describe networks of small size are still rare, and this prevents us to make progress in understanding neural dynamics at these intermediate scales. Here we develop a novel systematic analysis of the dynamics of arbitrarily small networks composed of homogeneous populations of excitatory and inhibitory firing-rate neurons. We study the local bifurcations of their neural activity with an approach that is largely analytically tractable, and we numerically determine the global bifurcations. We find that for strong inhibition these networks give rise to very complex dynamics, caused by the formation of multiple branching solutions of the neural dynamics equations that emerge through spontaneous symmetry-breaking. This qualitative change of the neural dynamics is a finite-size effect of the network, that reveals qualitative and previously unexplored differences between mesoscopic cortical circuits and their mean-field approximation. The most important consequence of spontaneous symmetry-breaking is the ability of mesoscopic networks to regulate their degree of functional heterogeneity, which is thought to help reducing the detrimental effect of noise correlations on cortical information processing.

  19. Neural processing of gustatory information in insular circuits.

    Science.gov (United States)

    Maffei, Arianna; Haley, Melissa; Fontanini, Alfredo

    2012-08-01

    The insular cortex is the primary cortical site devoted to taste processing. A large body of evidence is available for how insular neurons respond to gustatory stimulation in both anesthetized and behaving animals. Most of the reports describe broadly tuned neurons that are involved in processing the chemosensory, physiological and psychological aspects of gustatory experience. However little is known about how these neural responses map onto insular circuits. Particularly mysterious is the functional role of the three subdivisions of the insular cortex: the granular, the dysgranular and the agranular insular cortices. In this article we review data on the organization of the local and long-distance circuits in the three subdivisions. The functional significance of these results is discussed in light of the latest electrophysiological data. A view of the insular cortex as a functionally integrated system devoted to processing gustatory, multimodal, cognitive and affective information is proposed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. The neural dynamics of reward value and risk coding in the human orbitofrontal cortex.

    Science.gov (United States)

    Li, Yansong; Vanni-Mercier, Giovanna; Isnard, Jean; Mauguière, François; Dreher, Jean-Claude

    2016-04-01

    The orbitofrontal cortex is known to carry information regarding expected reward, risk and experienced outcome. Yet, due to inherent limitations in lesion and neuroimaging methods, the neural dynamics of these computations has remained elusive in humans. Here, taking advantage of the high temporal definition of intracranial recordings, we characterize the neurophysiological signatures of the intact orbitofrontal cortex in processing information relevant for risky decisions. Local field potentials were recorded from the intact orbitofrontal cortex of patients suffering from drug-refractory partial epilepsy with implanted depth electrodes as they performed a probabilistic reward learning task that required them to associate visual cues with distinct reward probabilities. We observed three successive signals: (i) around 400 ms after cue presentation, the amplitudes of the local field potentials increased with reward probability; (ii) a risk signal emerged during the late phase of reward anticipation and during the outcome phase; and (iii) an experienced value signal appeared at the time of reward delivery. Both the medial and lateral orbitofrontal cortex encoded risk and reward probability while the lateral orbitofrontal cortex played a dominant role in coding experienced value. The present study provides the first evidence from intracranial recordings that the human orbitofrontal cortex codes reward risk both during late reward anticipation and during the outcome phase at a time scale of milliseconds. Our findings offer insights into the rapid mechanisms underlying the ability to learn structural relationships from the environment. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Emotion and decision making: multiple modulatory neural circuits.

    Science.gov (United States)

    Phelps, Elizabeth A; Lempert, Karolina M; Sokol-Hessner, Peter

    2014-01-01

    Although the prevalent view of emotion and decision making is derived from the notion that there are dual systems of emotion and reason, a modulatory relationship more accurately reflects the current research in affective neuroscience and neuroeconomics. Studies show two potential mechanisms for affect's modulation of the computation of subjective value and decisions. Incidental affective states may carry over to the assessment of subjective value and the decision, and emotional reactions to the choice may be incorporated into the value calculation. In addition, this modulatory relationship is reciprocal: Changing emotion can change choices. This research suggests that the neural mechanisms mediating the relation between affect and choice vary depending on which affective component is engaged and which decision variables are assessed. We suggest that a detailed and nuanced understanding of emotion and decision making requires characterizing the multiple modulatory neural circuits underlying the different means by which emotion and affect can influence choices.

  2. Pulse coded biologically motivated neural-type MOS circuits

    Science.gov (United States)

    1991-11-01

    This project has two aspects, one for ONR and one for AFOSR. The ONR portion is devoted to obtaining hardware implementations for the physiological representations used in the program SYNETSIM developed by the neurophysiologist Dr. D. Hartline of Bekesy Laboratories. The AFOSR portion is for evaluation capabilities of the pulse code philosophy of neural networks. On the ONR portion of the research, several chips have been fabricated for SYNETSIM pools and a neural arithmetic unit based upon the pools. Also, a number of modifications have been made to SYNETSIM to make it a much more user-friendly program. Several papers have been presented at international conferences and the DRIVER module is under continued investigation for VLSI realization. The means to implement long term potentiation are also under continued investigation. On the AFOSR portion, a means of realizing any Hopfield-type network via pulse coded circuits was obtained.

  3. Generating three-qubit quantum circuits with neural networks

    Science.gov (United States)

    Swaddle, Michael; Noakes, Lyle; Smallbone, Harry; Salter, Liam; Wang, Jingbo

    2017-10-01

    A new method for compiling quantum algorithms is proposed and tested for a three qubit system. The proposed method is to decompose a unitary matrix U, into a product of simpler Uj via a neural network. These Uj can then be decomposed into product of known quantum gates. Key to the effectiveness of this approach is the restriction of the set of training data generated to paths which approximate minimal normal subRiemannian geodesics, as this removes unnecessary redundancy and ensures the products are unique. The two neural networks are shown to work effectively, each individually returning low loss values on validation data after relatively short training periods. The two networks are able to return coefficients that are sufficiently close to the true coefficient values to validate this method as an approach for generating quantum circuits. There is scope for more work in scaling this approach for larger quantum systems.

  4. Common and distinct neural features of social and non-social reward processing in autism and social anxiety disorder.

    Science.gov (United States)

    Richey, John A; Rittenberg, Alison; Hughes, Lauren; Damiano, Cara R; Sabatino, Antoinette; Miller, Stephanie; Hanna, Eleanor; Bodfish, James W; Dichter, Gabriel S

    2014-03-01

    Autism spectrum disorders (ASDs) and social anxiety disorder (SAD) are both characterized by social dysfunction, but no study to date has compared neural responses to social rewards in ASDs and SAD. Neural responses during social and non-social reward anticipation and outcomes were examined in individuals with ASD (n = 16), SAD (n = 15) and a control group (n = 19) via functional magnetic resonance imaging. Analyses modeling all three groups revealed increased nucleus accumbens (NAc) activation in SAD relative to ASD during monetary reward anticipation, whereas both the SAD and ASD group demonstrated decreased bilateral NAc activation relative to the control group during social reward anticipation. During reward outcomes, the SAD group did not differ significantly from the other two groups in ventromedial prefrontal cortex activation to either reward type. Analyses comparing only the ASD and SAD groups revealed greater bilateral amygdala activation to social rewards in SAD relative to ASD during both anticipation and outcome phases, and the magnitude of left amygdala hyperactivation in the SAD group during social reward anticipation was significantly correlated with the severity of trait anxiety symptoms. Results suggest reward network dysfunction to both monetary and social rewards in SAD and ASD during reward anticipation and outcomes, but that NAc hypoactivation during monetary reward anticipation differentiates ASD from SAD.

  5. A breathing circuit alarm system based on neural networks.

    Science.gov (United States)

    Orr, J A; Westenskow, D R

    1994-03-01

    The objectives of our study were (1) to implement intelligent respiratory alarms with a neural network; and (2) to increase alarm specificity and decrease false-alarm rates compared with current alarms. We trained a neural network to recognize 13 faults in an anesthesia breathing circuit. The system extracted 30 breath-to-breath features from the airway CO2, flow, and pressure signals. We created training data for the network by introducing 13 faults repeatedly in 5 dogs (616 total faults). We used the data to train the neural network using the backward error propagation algorithm. In animals, the trained network reported the alarms correctly for 95.0% of the faults when tested during controlled ventilation, and for 86.9% of the faults during spontaneous breathing. When tested in the operating room, the system found and correctly reported 54 of 57 faults that occurred during 43.6 hr of use. The alarm system produced a total of 74 false alarms during 43.6 hr of monitoring. Neural networks may be useful in creating intelligent anesthesia alarm systems.

  6. Impaired neural reward processing in children and adolescents with reactive attachment disorder: A pilot study.

    Science.gov (United States)

    Mizuno, Kei; Takiguchi, Shinichiro; Yamazaki, Mika; Asano, Mizuki; Kato, Shiho; Kuriyama, Kikuko; Watanabe, Yasuyoshi; Sadato, Norihiro; Tomoda, Akemi

    2015-10-01

    Reactive attachment disorder (RAD) is characterized by markedly disturbed and developmentally inappropriate social relatedness due to parental maltreatment. RAD patients often display a high number of comorbid attention deficit/hyperactivity disorder (ADHD) symptoms, and certain RAD symptoms are difficult to discriminate from ADHD. One of the core characteristics of ADHD is a decrease in neural reward processing due to dopamine dysfunction. The aim of the present study was to determine whether the brain activity involved in reward processing in RAD patients is impaired in comparison with ADHD patients and typically developed controls. Five RAD patients, 17 typically developed (TD) controls and 17 ADHD patients aged 10-16 years performed tasks with high and low monetary reward while undergoing functional magnetic resonance imaging. ADHD patients were tested before and after 3 months treatment with osmotic release oral system-methylphenidate. Before treatment, ADHD patients showed that striatal and thalamus activities only in the tasks with low monetary reward were lower than TD controls. RAD patients showed decrease in activity of the caudate, putamen and thalamus during both the high and low monetary reward conditions in comparison with all the other groups. In RAD patients, the activity of the putamen was associated with the severity of posttraumatic stress and overt dissociation. Reward sensitivity was markedly decreased in children and adolescents with RAD, as evidenced by a diminished neural response during reward perception. This suggests that dopaminergic dysfunction exists in these patients, and may inform future dopaminergic treatment strategies for RAD. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Adolescent neural response to reward is related to participant sex and task motivation.

    Science.gov (United States)

    Alarcón, Gabriela; Cservenka, Anita; Nagel, Bonnie J

    2017-02-01

    Risky decision making is prominent during adolescence, perhaps contributed to by heightened sensation seeking and ongoing maturation of reward and dopamine systems in the brain, which are, in part, modulated by sex hormones. In this study, we examined sex differences in the neural substrates of reward sensitivity during a risky decision-making task and hypothesized that compared with girls, boys would show heightened brain activation in reward-relevant regions, particularly the nucleus accumbens, during reward receipt. Further, we hypothesized that testosterone and estradiol levels would mediate this sex difference. Moreover, we predicted boys would make more risky choices on the task. While boys showed increased nucleus accumbens blood oxygen level-dependent (BOLD) response relative to girls, sex hormones did not mediate this effect. As predicted, boys made a higher percentage of risky decisions during the task. Interestingly, boys also self-reported more motivation to perform well and earn money on the task, while girls self-reported higher state anxiety prior to the scan session. Motivation to earn money partially mediated the effect of sex on nucleus accumbens activity during reward. Previous research shows that increased motivation and salience of reinforcers is linked with more robust striatal BOLD response, therefore psychosocial factors, in addition to sex, may play an important role in reward sensitivity. Elucidating neurobiological mechanisms that support adolescent sex differences in risky decision making has important implications for understanding individual differences that lead to advantageous and adverse behaviors that affect health outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Neural sensitivity to social reward and punishment anticipation in Social Anxiety Disorder.

    Directory of Open Access Journals (Sweden)

    Henk eCremers

    2015-01-01

    Full Text Available An imbalance in the neural motivational system may underlie Social Anxiety Disorder (SAD. This study examines social reward and punishment anticipation in SAD, predicting a valence-specific effect: increased striatal activity for punishment avoidance compared to obtaining a reward. Individuals with SAD (n=20 and age, gender, and education case-matched controls (n=20 participated in a functional magnetic resonance imaging (fMRI study. During fMRI scanning, participants performed a Social Incentive Delay task to measure the anticipation of social reward and punishment. The left putamen (part of the striatum showed a valence-specific interaction with group after correcting for medication use and comorbidity. The control group showed a relatively stronger activation for reward vs. punishment trials, compared to the social anxiety group. However, post-hoc pairwise comparisons were not significant, indicating that the effect is driven by a relative difference. A connectivity analysis (Psychophysiological interaction further revealed a general salience effect: SAD patients showed decreased putamen-ACC connectivity compared to controls for both reward and punishment trials. Together these results suggest that the usual motivational preference for social reward is absent in SAD. In addition, cortical control processes during social incentive anticipation may be disrupted in SAD. These results provide initial evidence for altered striatal involvement in both valence-specific and valence nonspecific processing of social incentives, and stress the relevance of taking motivational processes into account when studying social anxiety.

  9. Activity-dependent modulation of neural circuit synaptic connectivity

    Directory of Open Access Journals (Sweden)

    Charles R Tessier

    2009-07-01

    Full Text Available In many nervous systems, the establishment of neural circuits is known to proceed via a two-stage process; 1 early, activity-independent wiring to produce a rough map characterized by excessive synaptic connections, and 2 subsequent, use-dependent pruning to eliminate inappropriate connections and reinforce maintained synapses. In invertebrates, however, evidence of the activity-dependent phase of synaptic refinement has been elusive, and the dogma has long been that invertebrate circuits are “hard-wired” in a purely activity-independent manner. This conclusion has been challenged recently through the use of new transgenic tools employed in the powerful Drosophila system, which have allowed unprecedented temporal control and single neuron imaging resolution. These recent studies reveal that activity-dependent mechanisms are indeed required to refine circuit maps in Drosophila during precise, restricted windows of late-phase development. Such mechanisms of circuit refinement may be key to understanding a number of human neurological diseases, including developmental disorders such as Fragile X syndrome (FXS and autism, which are hypothesized to result from defects in synaptic connectivity and activity-dependent circuit function. This review focuses on our current understanding of activity-dependent synaptic connectivity in Drosophila, primarily through analyzing the role of the fragile X mental retardation protein (FMRP in the Drosophila FXS disease model. The particular emphasis of this review is on the expanding array of new genetically-encoded tools that are allowing cellular events and molecular players to be dissected with ever greater precision and detail.

  10. The influence of personality on neural mechanisms of observational fear and reward learning.

    Science.gov (United States)

    Hooker, Christine I; Verosky, Sara C; Miyakawa, Asako; Knight, Robert T; D'Esposito, Mark

    2008-09-01

    Fear and reward learning can occur through direct experience or observation. Both channels can enhance survival or create maladaptive behavior. We used fMRI to isolate neural mechanisms of observational fear and reward learning and investigate whether neural response varied according to individual differences in neuroticism and extraversion. Participants learned object-emotion associations by observing a woman respond with fearful (or neutral) and happy (or neutral) facial expressions to novel objects. The amygdala-hippocampal complex was active when learning the object-fear association, and the hippocampus was active when learning the object-happy association. After learning, objects were presented alone; amygdala activity was greater for the fear (vs. neutral) and happy (vs. neutral) associated object. Importantly, greater amygdala-hippocampal activity during fear (vs. neutral) learning predicted better recognition of learned objects on a subsequent memory test. Furthermore, personality modulated neural mechanisms of learning. Neuroticism positively correlated with neural activity in the amygdala and hippocampus during fear (vs. neutral) learning. Low extraversion/high introversion was related to faster behavioral predictions of the fearful and neutral expressions during fear learning. In addition, low extraversion/high introversion was related to greater amygdala activity during happy (vs. neutral) learning, happy (vs. neutral) object recognition, and faster reaction times for predicting happy and neutral expressions during reward learning. These findings suggest that neuroticism is associated with an increased sensitivity in the neural mechanism for fear learning which leads to enhanced encoding of fear associations, and that low extraversion/high introversion is related to enhanced conditionability for both fear and reward learning.

  11. What can the monetary incentive delay task tell us about the neural processing of reward and punishment?

    Directory of Open Access Journals (Sweden)

    Lutz K

    2014-04-01

    Full Text Available Kai Lutz,1–3 Mario Widmer1,2,41Department of Neurology, University Hospital Zürich, Zürich, 2Cereneo, Center for Neurology and Rehabilitation, Vitznau, 3Division of Neuropsychology, Institute of Psychology, University of Zürich, Zürich, 4Neural Control of Movement Lab, ETH Zürich, Zürich, SwitzerlandAbstract: Since its introduction in 2000, the monetary incentive delay (MID task has been used extensively to investigate changes in neural activity in response to the processing of reward and punishment in healthy, but also in clinical populations. Typically, the MID task requires an individual to react to a target stimulus presented after an incentive cue to win or to avoid losing the indicated reward. In doing so, this paradigm allows the detailed examination of different stages of reward processing like reward prediction, anticipation, outcome processing, and consumption as well as the processing of tasks under different reward conditions. This review gives an overview of different utilizations of the MID task by outlining the neuronal processes involved in distinct aspects of human reward processing, such as anticipation versus consumption, reward versus punishment, and, with a special focus, reward-based learning processes. Furthermore, literature on specific influences on reward processing like behavioral, clinical and developmental influences, is reviewed, describing current findings and possible future directions.Keywords: reward, punishment, dopamine, reward system

  12. Photovoltaic Pixels for Neural Stimulation: Circuit Models and Performance.

    Science.gov (United States)

    Boinagrov, David; Lei, Xin; Goetz, Georges; Kamins, Theodore I; Mathieson, Keith; Galambos, Ludwig; Harris, James S; Palanker, Daniel

    2016-02-01

    Photovoltaic conversion of pulsed light into pulsed electric current enables optically-activated neural stimulation with miniature wireless implants. In photovoltaic retinal prostheses, patterns of near-infrared light projected from video goggles onto subretinal arrays of photovoltaic pixels are converted into patterns of current to stimulate the inner retinal neurons. We describe a model of these devices and evaluate the performance of photovoltaic circuits, including the electrode-electrolyte interface. Characteristics of the electrodes measured in saline with various voltages, pulse durations, and polarities were modeled as voltage-dependent capacitances and Faradaic resistances. The resulting mathematical model of the circuit yielded dynamics of the electric current generated by the photovoltaic pixels illuminated by pulsed light. Voltages measured in saline with a pipette electrode above the pixel closely matched results of the model. Using the circuit model, our pixel design was optimized for maximum charge injection under various lighting conditions and for different stimulation thresholds. To speed discharge of the electrodes between the pulses of light, a shunt resistor was introduced and optimized for high frequency stimulation.

  13. Hormonal and neural mechanisms of food reward, eating behaviour and obesity.

    Science.gov (United States)

    Murray, Susan; Tulloch, Alastair; Gold, Mark S; Avena, Nicole M

    2014-09-01

    With rising rates of obesity, research continues to explore the contributions of homeostatic and hedonic mechanisms related to eating behaviour. In this Review, we synthesize the existing information on select biological mechanisms associated with reward-related food intake, dealing primarily with consumption of highly palatable foods. In addition to their established functions in normal feeding, three primary peripheral hormones (leptin, ghrelin and insulin) play important parts in food reward. Studies in laboratory animals and humans also show relationships between hyperphagia or obesity and neural pathways involved in reward. These findings have prompted questions regarding the possibility of addictive-like aspects in food consumption. Further exploration of this topic may help to explain aberrant eating patterns, such as binge eating, and provide insight into the current rates of overweight and obesity.

  14. Perceptual Competition Promotes Suppression of Reward Salience in Behavioral Selection and Neural Representation.

    Science.gov (United States)

    Gong, Mengyuan; Jia, Ke; Li, Sheng

    2017-06-28

    Visual attentional selection is influenced by the value of objects. Previous studies have demonstrated that reward-associated items lead to rapid distraction and associated behavioral costs, which are difficult to override with top-down control. However, it has not been determined whether a perceptually competitive environment could render the reward-driven distraction more susceptible to top-down suppression. Here, we trained both genders of human subjects to associate two orientations with high and low magnitudes of reward. After training, we collected fMRI data while the subjects performed a categorical visual search task. The item in the reward-associated orientation served as the distractor, and the relative physical salience between the target and distractor was carefully controlled to modulate the degree of perceptual competition. The behavioral results showed faster searches in the presence of high, relative to low, reward-associated distractors. However, this effect was evident only if the physical salience of the distractor was higher than that of the target, indicating a context-dependent suppression effect of reward salience that relied on high perceptual competition. By analyzing the fMRI data in primary visual cortex, we found that the behavioral pattern of results could be predicted by the suppressed channel responses tuned to the reward-associated orientation in the distractor location, accompanied by increased responses in the midbrain dopaminergic region. Our results suggest that the learned salience of a reward plays a flexible role in solving perceptual competition, enabling the neural system to adaptively modulate the perceptual representation for behavioral optimization.SIGNIFICANCE STATEMENT The predictiveness principle in learning theory suggests that the stimulus with high predictability of reward receives priority in attentional selection. This selection bias leads to difficulties in changing approach behaviors, and thus becomes an

  15. Evolving Neural Turing Machines for Reward-based Learning

    DEFF Research Database (Denmark)

    Greve, Rasmus Boll; Jacobsen, Emil Juul; Risi, Sebastian

    2016-01-01

    and integrating new information without losing previously acquired skills. Here we build on recent work by Graves et al. [5] who extended the capabilities of an ANN by combining it with an external memory bank trained through gradient descent. In this paper, we introduce an evolvable version of their Neural...... version of the double T-Maze, a complex reinforcement-like learning problem. In the T-Maze learning task the agent uses the memory bank to display adaptive behavior that normally requires a plastic ANN, thereby suggesting a complementary and effective mechanism for adaptive behavior in NE....

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

    Directory of Open Access Journals (Sweden)

    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.

  17. An integrated modelling framework for neural circuits with multiple neuromodulators.

    Science.gov (United States)

    Joshi, Alok; Youssofzadeh, Vahab; Vemana, Vinith; McGinnity, T M; Prasad, Girijesh; Wong-Lin, KongFatt

    2017-01-01

    Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. © 2017 The Authors.

  18. Shared neural circuits for mentalizing about the self and others.

    Science.gov (United States)

    Lombardo, Michael V; Chakrabarti, Bhismadev; Bullmore, Edward T; Wheelwright, Sally J; Sadek, Susan A; Suckling, John; Baron-Cohen, Simon

    2010-07-01

    Although many examples exist for shared neural representations of self and other, it is unknown how such shared representations interact with the rest of the brain. Furthermore, do high-level inference-based shared mentalizing representations interact with lower level embodied/simulation-based shared representations? We used functional neuroimaging (fMRI) and a functional connectivity approach to assess these questions during high-level inference-based mentalizing. Shared mentalizing representations in ventromedial prefrontal cortex, posterior cingulate/precuneus, and temporo-parietal junction (TPJ) all exhibited identical functional connectivity patterns during mentalizing of both self and other. Connectivity patterns were distributed across low-level embodied neural systems such as the frontal operculum/ventral premotor cortex, the anterior insula, the primary sensorimotor cortex, and the presupplementary motor area. These results demonstrate that identical neural circuits are implementing processes involved in mentalizing of both self and other and that the nature of such processes may be the integration of low-level embodied processes within higher level inference-based mentalizing.

  19. Neural connectivity during reward expectation dissociates psychopathic criminals from non-criminal individuals with high impulsive/antisocial psychopathic traits

    NARCIS (Netherlands)

    Geurts, D.E.; Borries, K. von; Volman, I.; Bulten, B.H.; Cools, R.; Verkes, R.J.

    2016-01-01

    Criminal behaviour poses a big challenge for society. A thorough understanding of the neurobiological mechanisms underlying criminality could optimize its prevention and management. Specifically,elucidating the neural mechanisms underpinning reward expectation might be pivotal to understanding

  20. Distributed neural representation of saliency controlled value and category during anticipation of rewards and punishments.

    Science.gov (United States)

    Zhang, Zhihao; Fanning, Jennifer; Ehrlich, Daniel B; Chen, Wenting; Lee, Daeyeol; Levy, Ifat

    2017-12-04

    An extensive literature from cognitive neuroscience examines the neural representation of value, but interpretations of these existing results are often complicated by the potential confound of saliency. At the same time, recent attempts to dissociate neural signals of value and saliency have not addressed their relationship with category information. Using a multi-category valuation task that incorporates rewards and punishments of different nature, we identify distributed neural representation of value, saliency, and category during outcome anticipation. Moreover, we reveal category encoding in multi-voxel blood-oxygen-level-dependent activity patterns of the vmPFC and the striatum that coexist with value signals. These results help clarify ambiguities regarding value and saliency encoding in the human brain and their category independence, lending strong support to the neural "common currency" hypothesis. Our results also point to potential novel mechanisms of integrating multiple aspects of decision-related information.

  1. 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...

  2. Neural circuits mediating olfactory-driven behavior in fish

    Science.gov (United States)

    Kermen, Florence; Franco, Luis M.; Wyatt, Cameron; Yaksi, Emre

    2013-01-01

    The fish olfactory system processes odor signals and mediates behaviors that are crucial for survival such as foraging, courtship, and alarm response. Although the upstream olfactory brain areas (olfactory epithelium and olfactory bulb) are well-studied, less is known about their target brain areas and the role they play in generating odor-driven behaviors. Here we review a broad range of literature on the anatomy, physiology, and behavioral output of the olfactory system and its target areas in a wide range of teleost fish. Additionally, we discuss how applying recent technological advancements to the zebrafish (Danio rerio) could help in understanding the function of these target areas. We hope to provide a framework for elucidating the neural circuit computations underlying the odor-driven behaviors in this small, transparent, and genetically amenable vertebrate. PMID:23596397

  3. Two multichannel integrated circuits for neural recording and signal processing.

    Science.gov (United States)

    Obeid, Iyad; Morizio, James C; Moxon, Karen A; Nicolelis, Miguel A L; Wolf, Patrick D

    2003-02-01

    We have developed, manufactured, and tested two analog CMOS integrated circuit "neurochips" for recording from arrays of densely packed neural electrodes. Device A is a 16-channel buffer consisting of parallel noninverting amplifiers with a gain of 2 V/V. Device B is a 16-channel two-stage analog signal processor with differential amplification and high-pass filtering. It features selectable gains of 250 and 500 V/V as well as reference channel selection. The resulting amplifiers on Device A had a mean gain of 1.99 V/V with an equivalent input noise of 10 microV(rms). Those on Device B had mean gains of 53.4 and 47.4 dB with a high-pass filter pole at 211 Hz and an equivalent input noise of 4.4 microV(rms). Both devices were tested in vivo with electrode arrays implanted in the somatosensory cortex.

  4. Long-Lasting Neural Circuit Dysfunction Following Developmental Ethanol Exposure

    Directory of Open Access Journals (Sweden)

    Mariko Saito

    2013-04-01

    Full Text Available Fetal Alcohol Spectrum Disorder (FASD is a general diagnosis for those exhibiting long-lasting neurobehavioral and cognitive deficiencies as a result of fetal alcohol exposure. It is among the most common causes of mental deficits today. Those impacted are left to rely on advances in our understanding of the nature of early alcohol-induced disorders toward human therapies. Research findings over the last decade have developed a model where ethanol-induced neurodegeneration impacts early neural circuit development, thereby perpetuating subsequent integration and plasticity in vulnerable brain regions. Here we review our current knowledge of FASD neuropathology based on discoveries of long-lasting neurophysiological effects of acute developmental ethanol exposure in animal models. We discuss the important balance between synaptic excitation and inhibition in normal neural network function, and relate the significance of that balance to human FASD as well as related disease states. Finally, we postulate that excitation/inhibition imbalance caused by early ethanol-induced neurodegeneration results in perturbed local and regional network signaling and therefore neurobehavioral pathology.

  5. Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.; Baler, R.

    2010-07-01

    Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co-opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction.

  6. High-frequency stimulation of nucleus accumbens changes in dopaminergic reward circuit.

    Directory of Open Access Journals (Sweden)

    Na Yan

    morphine-sham stimulation group compared with the morphine-only group. These findings indicated that unilateral NAc stimulation inhibits the morphine-induced rats associated hyperactivation of excitatory neurotransmission in the mesocorticolimbic reward circuit.

  7. Age associations with neural processing of reward anticipation in adolescents with bipolar disorders

    Directory of Open Access Journals (Sweden)

    Snežana Urošević

    2016-01-01

    Full Text Available Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI protocol using the Monetary Incentive Delay (MID task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex. Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus, suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development.

  8. Age associations with neural processing of reward anticipation in adolescents with bipolar disorders.

    Science.gov (United States)

    Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B; Youngstrom, Eric A; Thomas, Kathleen M

    2016-01-01

    Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development.

  9. Neural evidence for description dependent reward processing in the framing effect

    Directory of Open Access Journals (Sweden)

    Rongjun eYu

    2014-03-01

    Full Text Available Human decision making can be influenced by emotionally valenced contexts, known as the framing effect. We used event-related brain potentials to investigate how framing influences the encoding of reward. We found that the feedback related negativity (FRN, which indexes the worse than expected negative prediction error in the anterior cingulate cortex, was more negative for the negative frame than for the positive frame in the win domain. Consistent with previous findings that the FRN is not sensitive to better than expected positive prediction error, the FRN did not differentiate the positive and negative frame in the loss domain. Our results provide neural evidence that the description invariance principle which states that reward representation and decision making are not influenced by how options are presented is violated in the framing effect.

  10. Timing matters: Using optogenetics to chronically manipulate neural circuits and rhythms

    Directory of Open Access Journals (Sweden)

    Michelle M Sidor

    2014-02-01

    Full Text Available The ability to probe defined neural circuits with both the spatial and temporal resolution imparted by optogenetics has transformed the field of neuroscience. Although much attention has been paid to the advantages of manipulating neural activity at millisecond timescales in order to elicit time-locked neural responses, little consideration has been given to the manipulation of circuit activity at physiologically relevant times of day, across multiple days. Nearly all biological events are governed by the circadian clock and exhibit 24-hour rhythms in activity. Indeed, neural circuit activity itself exhibits a daily rhythm with distinct temporal peaks in activity occurring at specific times of the day. Therefore, experimentally probing circuit function within and across physiologically relevant time windows (minutes to hours in behaving animals is fundamental to understanding the function of any one particular circuit within the intact brain. Furthermore, understanding how circuit function changes with repeated manipulation is important for modeling the circuit-wide disruptions that occur with chronic disease states. Here, we review recent advances in optogenetic technology that allow for chronic, temporally specific, control of circuit activity and provide examples of chronic optogenetic paradigms that have been utilized in the search for the neural circuit basis of behaviors relevant to human neuropsychiatric disease.

  11. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

    Science.gov (United States)

    Webber, Emily S; Mankin, David E; Cromwell, Howard C

    2016-01-01

    The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

  12. A neural circuit covarying with social hierarchy in macaques.

    Directory of Open Access Journals (Sweden)

    MaryAnn P Noonan

    2014-09-01

    Full Text Available Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI, which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI data in 25 group-living macaques. First, a deformation-based morphometric (DBM approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

  13. Clustered Protocadherins Are Required for Building Functional Neural Circuits

    Science.gov (United States)

    Hasegawa, Sonoko; Kobayashi, Hiroaki; Kumagai, Makiko; Nishimaru, Hiroshi; Tarusawa, Etsuko; Kanda, Hiro; Sanbo, Makoto; Yoshimura, Yumiko; Hirabayashi, Masumi; Hirabayashi, Takahiro; Yagi, Takeshi

    2017-01-01

    Neuronal identity is generated by the cell-surface expression of clustered protocadherin (Pcdh) isoforms. In mice, 58 isoforms from three gene clusters, Pcdhα, Pcdhβ, and Pcdhγ, are differentially expressed in neurons. Since cis-heteromeric Pcdh oligomers on the cell surface interact homophilically with that in other neurons in trans, it has been thought that the Pcdh isoform repertoire determines the binding specificity of synapses. We previously described the cooperative functions of isoforms from all three Pcdh gene clusters in neuronal survival and synapse formation in the spinal cord. However, the neuronal loss and the following neonatal lethality prevented an analysis of the postnatal development and characteristics of the clustered-Pcdh-null (Δαβγ) neural circuits. Here, we used two methods, one to generate the chimeric mice that have transplanted Δαβγ neurons into mouse embryos, and the other to generate double mutant mice harboring null alleles of both the Pcdh gene and the proapoptotic gene Bax to prevent neuronal loss. First, our results showed that the surviving chimeric mice that had a high contribution of Δαβγ cells exhibited paralysis and died in the postnatal period. An analysis of neuronal survival in postnatally developing brain regions of chimeric mice clarified that many Δαβγ neurons in the forebrain were spared from apoptosis, unlike those in the reticular formation of the brainstem. Second, in Δαβγ/Bax null double mutants, the central pattern generator (CPG) for locomotion failed to create a left-right alternating pattern even in the absence of neurodegeneraton. Third, calcium imaging of cultured hippocampal neurons showed that the network activity of Δαβγ neurons tended to be more synchronized and lost the variability in the number of simultaneously active neurons observed in the control network. Lastly, a comparative analysis for trans-homophilic interactions of the exogenously introduced single Pcdh-γA3 isoforms

  14. Clustered Protocadherins Are Required for Building Functional Neural Circuits

    Directory of Open Access Journals (Sweden)

    Takeshi Yagi

    2017-04-01

    Full Text Available Neuronal identity is generated by the cell-surface expression of clustered protocadherin (Pcdh isoforms. In mice, 58 isoforms from three gene clusters, Pcdhα, Pcdhβ, and Pcdhγ, are differentially expressed in neurons. Since cis-heteromeric Pcdh oligomers on the cell surface interact homophilically with that in other neurons in trans, it has been thought that the Pcdh isoform repertoire determines the binding specificity of synapses. We previously described the cooperative functions of isoforms from all three Pcdh gene clusters in neuronal survival and synapse formation in the spinal cord. However, the neuronal loss and the following neonatal lethality prevented an analysis of the postnatal development and characteristics of the clustered-Pcdh-null (Δαβγ neural circuits. Here, we used two methods, one to generate the chimeric mice that have transplanted Δαβγ neurons into mouse embryos, and the other to generate double mutant mice harboring null alleles of both the Pcdh gene and the proapoptotic gene Bax to prevent neuronal loss. First, our results showed that the surviving chimeric mice that had a high contribution of Δαβγ cells exhibited paralysis and died in the postnatal period. An analysis of neuronal survival in postnatally developing brain regions of chimeric mice clarified that many Δαβγ neurons in the forebrain were spared from apoptosis, unlike those in the reticular formation of the brainstem. Second, in Δαβγ/Bax null double mutants, the central pattern generator (CPG for locomotion failed to create a left-right alternating pattern even in the absence of neurodegeneraton. Third, calcium imaging of cultured hippocampal neurons showed that the network activity of Δαβγ neurons tended to be more synchronized and lost the variability in the number of simultaneously active neurons observed in the control network. Lastly, a comparative analysis for trans-homophilic interactions of the exogenously introduced single

  15. Neural circuit mechanisms of short-term memory

    Science.gov (United States)

    Goldman, Mark

    Memory over time scales of seconds to tens of seconds is thought to be maintained by neural activity that is triggered by a memorized stimulus and persists long after the stimulus is turned off. This presents a challenge to current models of memory-storing mechanisms, because the typical time scales associated with cellular and synaptic dynamics are two orders of magnitude smaller than this. While such long time scales can easily be achieved by bistable processes that toggle like a flip-flop between a baseline and elevated-activity state, many neuronal systems have been observed experimentally to be capable of maintaining a continuum of stable states. For example, in neural integrator networks involved in the accumulation of evidence for decision making and in motor control, individual neurons have been recorded whose activity reflects the mathematical integral of their inputs; in the absence of input, these neurons sustain activity at a level proportional to the running total of their inputs. This represents an analog form of memory whose dynamics can be conceptualized through an energy landscape with a continuum of lowest-energy states. Such continuous attractor landscapes are structurally non-robust, in seeming violation of the relative robustness of biological memory systems. In this talk, I will present and compare different biologically motivated circuit motifs for the accumulation and storage of signals in short-term memory. Challenges to generating robust memory maintenance will be highlighted and potential mechanisms for ameliorating the sensitivity of memory networks to perturbations will be discussed. Funding for this work was provided by NIH R01 MH065034, NSF IIS-1208218, Simons Foundation 324260, and a UC Davis Ophthalmology Research to Prevent Blindness Grant.

  16. The sleep and circadian modulation of neural reward pathways: a protocol for a pair of systematic reviews.

    Science.gov (United States)

    Byrne, Jamie E M; Murray, Greg

    2017-12-02

    Animal research suggests that neural reward activation may be systematically modulated by sleep and circadian function. Whether humans also exhibit sleep and circadian modulation of neural reward pathways is unclear. This area is in need of further research, as it has implications for the involvement of sleep and circadian function in reward-related disorders. The aim of this paper is to describe the protocol for a pair of systematic literature reviews to synthesise existing literature related to (1) sleep and (2) circadian modulation of neural reward pathways in healthy human populations. A systematic review of relevant online databases (Scopus, PubMed, Web of Science, ProQuest, PsycINFO and EBSCOhost) will be conducted. Reference lists, relevant reviews and supplementary data will be searched for additional articles. Articles will be included if (a) they contain a sleep- or circadian-related predictor variable with a neural reward outcome variable, (b) use a functional magnetic resonance imaging protocol and (c) use human samples. Articles will be excluded if study participants had disorders known to affect the reward system. The articles will be screened by two independent authors. Two authors will complete the data extraction form, with two authors independently completing the quality assessment tool for the selected articles, with a consensus reached with a third author if needed. Narrative synthesis methods will be used to analyse the data. The findings from this pair of systematic literature reviews will assist in the identification of the pathways involved in the sleep and circadian function modulation of neural reward in healthy individuals, with implications for disorders characterised by dysregulation in sleep, circadian rhythms and reward function. PROSPERO CRD42017064994.

  17. Self-awareness in neurodegenerative disease relies on neural structures mediating reward-driven attention

    Science.gov (United States)

    Shany-Ur, Tal; Lin, Nancy; Rosen, Howard J.; Sollberger, Marc; Miller, Bruce L.

    2014-01-01

    overlooking versus exaggerating deficits, overestimation and underestimation scores were analysed separately, controlling for age, sex, total intracranial volume and extent of actual functional decline. Atrophy related to overestimating one’s functioning included bilateral, right greater than left frontal and subcortical regions, including dorsal superior and middle frontal gyri, lateral and medial orbitofrontal gyri, right anterior insula, putamen, thalamus, and caudate, and midbrain and pons. Thus, our patients’ tendency to under-represent their functional decline was related to degeneration of domain-general dorsal frontal regions involved in attention, as well as orbitofrontal and subcortical regions likely involved in assigning a reward value to self-related processing and maintaining accurate self-knowledge. The anatomic correlates of underestimation (right rostral anterior cingulate cortex, uncorrected significance level) were distinct from overestimation and had a substantially smaller effect size. This suggests that underestimation or ‘tarnishing’ may be influenced by non-structural neurobiological and sociocultural factors, and should not be considered to be on a continuum with overestimation or ‘polishing’ of functional capacity, which appears to be more directly mediated by neural circuit dysfunction. PMID:24951639

  18. Rapid neural circuit switching mediated by synaptic plasticity during neural morphallactic regeneration.

    Science.gov (United States)

    Lybrand, Zane R; Zoran, Mark J

    2012-09-01

    The aquatic oligochaete, Lumbriculus variegatus (Lumbriculidae), undergoes a rapid regenerative transformation of its neural circuits following body fragmentation. This type of nervous system plasticity, called neural morphallaxis, involves the remodeling of the giant fiber pathways that mediate rapid head and tail withdrawal behaviors. Extra- and intracellular electrophysiological recordings demonstrated that changes in cellular properties and synaptic connections underlie neurobehavioral plasticity during morphallaxis. Sensory-to-giant interneuron connections, undetectable prior to body injury, emerged within hours of segment amputation. The appearance of functional synaptic transmission was followed by interneuron activation, coupling of giant fiber spiking to motor outputs and overt segmental shortening. The onset of morphallactic plasticity varied along the body axis and emerged more rapidly in segments closer to regions of sensory field overlap between the two giant fiber pathways. The medial and lateral giant fibers were simultaneously activated during a transient phase of network remodeling. Thus, synaptic plasticity at sensory-to-giant interneuron connections mediates escape circuit morphallaxis in this regenerating annelid worm. Copyright © 2011 Wiley Periodicals, Inc.

  19. Dopaminergic control of motivation and reinforcement learning: a closed-circuit account for reward-oriented behavior.

    Science.gov (United States)

    Morita, Kenji; Morishima, Mieko; Sakai, Katsuyuki; Kawaguchi, Yasuo

    2013-05-15

    Humans and animals take actions quickly when they expect that the actions lead to reward, reflecting their motivation. Injection of dopamine receptor antagonists into the striatum has been shown to slow such reward-seeking behavior, suggesting that dopamine is involved in the control of motivational processes. Meanwhile, neurophysiological studies have revealed that phasic response of dopamine neurons appears to represent reward prediction error, indicating that dopamine plays central roles in reinforcement learning. However, previous attempts to elucidate the mechanisms of these dopaminergic controls have not fully explained how the motivational and learning aspects are related and whether they can be understood by the way the activity of dopamine neurons itself is controlled by their upstream circuitries. To address this issue, we constructed a closed-circuit model of the corticobasal ganglia system based on recent findings regarding intracortical and corticostriatal circuit architectures. Simulations show that the model could reproduce the observed distinct motivational effects of D1- and D2-type dopamine receptor antagonists. Simultaneously, our model successfully explains the dopaminergic representation of reward prediction error as observed in behaving animals during learning tasks and could also explain distinct choice biases induced by optogenetic stimulation of the D1 and D2 receptor-expressing striatal neurons. These results indicate that the suggested roles of dopamine in motivational control and reinforcement learning can be understood in a unified manner through a notion that the indirect pathway of the basal ganglia represents the value of states/actions at a previous time point, an empirically driven key assumption of our model.

  20. A target sample of adolescents and reward processing: same neural and behavioral correlates engaged in common paradigms?

    Science.gov (United States)

    Nees, Frauke; Vollstädt-Klein, Sabine; Fauth-Bühler, Mira; Steiner, Sabina; Mann, Karl; Poustka, Luise; Banaschewski, Tobias; Büchel, Christian; Conrod, Patricia J; Garavan, Hugh; Heinz, Andreas; Ittermann, Bernd; Artiges, Eric; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Smolka, Michael N; Struve, Maren; Loth, Eva; Schumann, Gunter; Flor, Herta

    2012-11-01

    Adolescence is a transition period that is assumed to be characterized by increased sensitivity to reward. While there is growing research on reward processing in adolescents, investigations into the engagement of brain regions under different reward-related conditions in one sample of healthy adolescents, especially in a target age group, are missing. We aimed to identify brain regions preferentially activated in a reaction time task (monetary incentive delay (MID) task) and a simple guessing task (SGT) in a sample of 14-year-old adolescents (N = 54) using two commonly used reward paradigms. Functional magnetic resonance imaging was employed during the MID with big versus small versus no win conditions and the SGT with big versus small win and big versus small loss conditions. Analyses focused on changes in blood oxygen level-dependent contrasts during reward and punishment processing in anticipation and feedback phases. We found clear magnitude-sensitive response in reward-related brain regions such as the ventral striatum during anticipation in the MID task, but not in the SGT. This was also true for reaction times. The feedback phase showed clear reward-related, but magnitude-independent, response patterns, for example in the anterior cingulate cortex, in both tasks. Our findings highlight neural and behavioral response patterns engaged in two different reward paradigms in one sample of 14-year-old healthy adolescents and might be important for reference in future studies investigating reward and punishment processing in a target age group.

  1. Altered Neural Efficiency of Decision Making During Temporal Reward Discounting in Anorexia Nervosa.

    Science.gov (United States)

    King, Joseph A; Geisler, Daniel; Bernardoni, Fabio; Ritschel, Franziska; Böhm, Ilka; Seidel, Maria; Mennigen, Eva; Ripke, Stephan; Smolka, Michael N; Roessner, Veit; Ehrlich, Stefan

    2016-11-01

    The ability of individuals with anorexia nervosa (AN) to resist hunger and restrict caloric intake is often believed to reflect an unusual amount of self-control. However, the underlying neural substrate is poorly understood, especially in adolescent patients. Functional magnetic resonance imaging was used during an intertemporal choice task to probe the hemodynamic correlates of a common measurement of self-control-delayed (monetary) reward discounting-in a sample of acutely ill, predominately adolescent female patients with AN (n = 31) and age-matched healthy controls (n = 31). Delayed discounting rates did not differ between the groups, but decision making was consistently faster in the AN group. Although no group differences in the neural correlates of reward valuation were evident, activation associated with decision making was decreased in the AN group, most notably in the lateral prefrontal and posterior parietal regions implicated in executive control. Follow-up analysis of difficult decisions showed decreased activation in the AN group in a region of the dorsal anterior cingulate cortex. Decreased activation in frontoparietal regions involved in decision making, but faster and more consistent choice behavior, suggests that the altered efficiency of neural resource allocation might underlie an increased level of self-control in AN. This pattern of neural activation and behavior might reflect an ingrained "habit" to sustain high-level proactive (anticipatory) cognitive control in AN, which in turn might compromise reactive control mechanisms needed to adapt to changing cognitive demands, such as when difficult decisions must be made. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Neural evidence for an association between social proficiency and sensitivity to social reward.

    Science.gov (United States)

    Gossen, Anna; Groppe, Sarah E; Winkler, Lina; Kohls, Gregor; Herrington, John; Schultz, Robert T; Gründer, Gerhard; Spreckelmeyer, Katja N

    2014-05-01

    Data from developmental psychology suggests a link between the growth of socio-emotional competences and the infant's sensitivity to the salience of social stimuli. The aim of the present study was to find evidence for this relationship in healthy adults. Thirty-five participants were recruited based on their score above the 85th or below the 15th percentile of the empathy quotient questionnaire (EQ, Baron-Cohen and Wheelwright, 2004). Functional magnetic resonance imaging (fMRI) was used to compare neural responses to cues of social and non-social (monetary) reward. When compared to the high-EQ group, the low-EQ group showed reduced activity of the brain s reward system, specifically the right nucleus accumbens, in response to cues predictive of social reward (videos showing gestures of approval)-but increased activation in this area for monetary incentives. Our data provide evidence for a link between self-reported deficits in social proficiency and reduced sensitivity to the motivational salience of positive social stimuli.

  3. Learning to minimize efforts versus maximizing rewards: computational principles and neural correlates.

    Science.gov (United States)

    Skvortsova, Vasilisa; Palminteri, Stefano; Pessiglione, Mathias

    2014-11-19

    The mechanisms of reward maximization have been extensively studied at both the computational and neural levels. By contrast, little is known about how the brain learns to choose the options that minimize action cost. In principle, the brain could have evolved a general mechanism that applies the same learning rule to the different dimensions of choice options. To test this hypothesis, we scanned healthy human volunteers while they performed a probabilistic instrumental learning task that varied in both the physical effort and the monetary outcome associated with choice options. Behavioral data showed that the same computational rule, using prediction errors to update expectations, could account for both reward maximization and effort minimization. However, these learning-related variables were encoded in partially dissociable brain areas. In line with previous findings, the ventromedial prefrontal cortex was found to positively represent expected and actual rewards, regardless of effort. A separate network, encompassing the anterior insula, the dorsal anterior cingulate, and the posterior parietal cortex, correlated positively with expected and actual efforts. These findings suggest that the same computational rule is applied by distinct brain systems, depending on the choice dimension-cost or benefit-that has to be learned. Copyright © 2014 the authors 0270-6474/14/3415621-10$15.00/0.

  4. Neural substrate for brain stimulation reward in the rat: cathodal and anodal strength-duration properties.

    Science.gov (United States)

    Matthews, G

    1977-08-01

    The trade-off between current strength and duration of a stimulating pulse was studied for the rewarding and priming effects of brain stimulation reward (BSR). With cathodal pulses, strenght-duration functions for BSR had chronaxies of .8-3 msec. No differences were observed between the results for rewarding and priming effects. With anodal pulses. strength-duration curves were parallel to the cathodal curves at pulse durations of .1-5 msec, but at pulse durations greater than 5 msec the anodal curves showed a greater drop in required current intensity than did the cathodal curves. The parallel portion of the anodal curves was interpreted as due to anode-make excitation, and the drop at longer pulse durations was interpreted as due to anode-break excitation. Cathodal strength-duration functions for the motor effect elicited through the BSR electrodes had chronaxies of .15-.48 msec. Measurements of the latency of the muscle twitch confirmed that anode-make and anode-break excitation occurred, the latter becoming evident at pulse durations as brief as .3-.4 msec. The results provide quantitative characterization of cathodal and anodal strength-duration properties of the neural substrate for BSR and are discussed in terms of their value in guiding electrophysiological investigation of that substrate.

  5. The pleasure of revenge: retaliatory aggression arises from a neural imbalance toward reward.

    Science.gov (United States)

    Chester, David S; DeWall, C Nathan

    2016-07-01

    Most of daily life hums along peacefully but provocations tip the balance toward aggression. Negative feelings are often invoked to explain why people lash out after an insult. Yet people might retaliate because provocation makes aggression hedonically rewarding. To test this alternative hypothesis, 69 participants underwent functional neuroimaging while they completed a behavioral aggression task that repeatedly manipulated whether aggression was preceded by an instance of provocation or not. After provocation, greater activity in the nucleus accumbens (NAcc) (a brain region reliably associated with reward) during aggressive decisions predicted louder noise blasts administered in retaliation. Greater NAcc activation was also associated with participants' history of real-world violence. Functional connectivity between the NAcc and a regulatory region in the lateral prefrontal cortex related to lower retaliatory aggression. These findings suggest that provocation tips the neural balance towards hedonic reward, which fosters retaliatory aggression. Although such pleasure of inflicting pain may promote retaliatory aggression, self-regulatory processes can keep such aggressive urges at bay. Implications for theory and violence reduction are discussed. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  6. Self-Organizing Neural Circuits for Sensory-Guided Motor Control

    National Research Council Canada - National Science Library

    Grossberg, Stephen

    1999-01-01

    The reported projects developed mathematical models to explain how self-organizing neural circuits that operate under continuous or intermittent sensory guidance achieve flexible and accurate control of human movement...

  7. 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

  8. Ultra low-power integrated circuit design for wireless neural interfaces

    CERN Document Server

    Holleman, Jeremy; Otis, Brian

    2014-01-01

    Presenting results from real prototype systems, this volume provides an overview of ultra low-power integrated circuits and systems for neural signal processing and wireless communication. Topics include analog, radio, and signal processing theory and design for ultra low-power circuits.

  9. Learning to Produce Syllabic Speech Sounds via Reward-Modulated Neural Plasticity.

    Science.gov (United States)

    Warlaumont, Anne S; Finnegan, Megan K

    2016-01-01

    At around 7 months of age, human infants begin to reliably produce well-formed syllables containing both consonants and vowels, a behavior called canonical babbling. Over subsequent months, the frequency of canonical babbling continues to increase. How the infant's nervous system supports the acquisition of this ability is unknown. Here we present a computational model that combines a spiking neural network, reinforcement-modulated spike-timing-dependent plasticity, and a human-like vocal tract to simulate the acquisition of canonical babbling. Like human infants, the model's frequency of canonical babbling gradually increases. The model is rewarded when it produces a sound that is more auditorily salient than sounds it has previously produced. This is consistent with data from human infants indicating that contingent adult responses shape infant behavior and with data from deaf and tracheostomized infants indicating that hearing, including hearing one's own vocalizations, is critical for canonical babbling development. Reward receipt increases the level of dopamine in the neural network. The neural network contains a reservoir with recurrent connections and two motor neuron groups, one agonist and one antagonist, which control the masseter and orbicularis oris muscles, promoting or inhibiting mouth closure. The model learns to increase the number of salient, syllabic sounds it produces by adjusting the base level of muscle activation and increasing their range of activity. Our results support the possibility that through dopamine-modulated spike-timing-dependent plasticity, the motor cortex learns to harness its natural oscillations in activity in order to produce syllabic sounds. It thus suggests that learning to produce rhythmic mouth movements for speech production may be supported by general cortical learning mechanisms. The model makes several testable predictions and has implications for our understanding not only of how syllabic vocalizations develop in

  10. Learning to Produce Syllabic Speech Sounds via Reward-Modulated Neural Plasticity

    Science.gov (United States)

    Warlaumont, Anne S.; Finnegan, Megan K.

    2016-01-01

    At around 7 months of age, human infants begin to reliably produce well-formed syllables containing both consonants and vowels, a behavior called canonical babbling. Over subsequent months, the frequency of canonical babbling continues to increase. How the infant’s nervous system supports the acquisition of this ability is unknown. Here we present a computational model that combines a spiking neural network, reinforcement-modulated spike-timing-dependent plasticity, and a human-like vocal tract to simulate the acquisition of canonical babbling. Like human infants, the model’s frequency of canonical babbling gradually increases. The model is rewarded when it produces a sound that is more auditorily salient than sounds it has previously produced. This is consistent with data from human infants indicating that contingent adult responses shape infant behavior and with data from deaf and tracheostomized infants indicating that hearing, including hearing one’s own vocalizations, is critical for canonical babbling development. Reward receipt increases the level of dopamine in the neural network. The neural network contains a reservoir with recurrent connections and two motor neuron groups, one agonist and one antagonist, which control the masseter and orbicularis oris muscles, promoting or inhibiting mouth closure. The model learns to increase the number of salient, syllabic sounds it produces by adjusting the base level of muscle activation and increasing their range of activity. Our results support the possibility that through dopamine-modulated spike-timing-dependent plasticity, the motor cortex learns to harness its natural oscillations in activity in order to produce syllabic sounds. It thus suggests that learning to produce rhythmic mouth movements for speech production may be supported by general cortical learning mechanisms. The model makes several testable predictions and has implications for our understanding not only of how syllabic vocalizations develop

  11. Neural Circuits via Which Single Prolonged Stress Exposure Leads to Fear Extinction Retention Deficits

    Science.gov (United States)

    Knox, Dayan; Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

    2016-01-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions…

  12. Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis

    Science.gov (United States)

    Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

    2016-01-01

    Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (Pbulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive–emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction. PMID:27801897

  13. Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

    Science.gov (United States)

    Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

    2016-11-01

    Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (Panorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

  14. Demonstration of a neural circuit critical for imprinting behavior in chicks.

    Science.gov (United States)

    Nakamori, Tomoharu; Sato, Katsushige; Atoji, Yasuro; Kanamatsu, Tomoyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

    2010-03-24

    Imprinting behavior in birds is elicited by visual and/or auditory cues. It has been demonstrated previously that visual cues are recognized and processed in the visual Wulst (VW), and imprinting memory is stored in the intermediate medial mesopallium (IMM) of the telencephalon. Alteration of neural responses in these two regions according to imprinting has been reported, yet direct evidence of the neural circuit linking these two regions is lacking. Thus, it remains unclear how memory is formed and expressed in this circuit. Here, we present anatomical as well as physiological evidence of the neural circuit connecting the VW and IMM and show that imprinting training during the critical period strengthens and refines this circuit. A functional connection established by imprint training resulted in an imprinting behavior. After the closure of the critical period, training could not activate this circuit nor induce the imprinting behavior. Glutamatergic neurons in the ventroposterior region of the VW, the core region of the hyperpallium densocellulare (HDCo), sent their axons to the periventricular part of the HD, just dorsal and afferent to the IMM. We found that the HDCo is important in imprinting behavior. The refinement and/or enhancement of this neural circuit are attributed to increased activity of HDCo cells, and the activity depended on NR2B-containing NMDA receptors. These findings show a neural connection in the telencephalon in Aves and demonstrate that NR2B function is indispensable for the plasticity of HDCo cells, which are key mediators of imprinting.

  15. Effect of maternal rumination and disengagement during childhood on offspring neural response to reward in late adolescence.

    Science.gov (United States)

    Morgan, Judith K; Shaw, Daniel S; Jacobs, Rachel H; Romens, Sarah E; Sitnick, Stephanie L; Forbes, Erika E

    2017-04-30

    Maternal rumination is a cognitive-affective trait that could influence offspring's ability to respond flexibly to positive and negative events, depending on the quality of maternal problem-solving behaviors with which rumination co-occurs. As reward circuitry is sensitive to stressors and related to risk for depression, reward circuitry is an appropriate candidate mechanism for how maternal characteristics influence offspring. We evaluated the independent and combined effect of maternal rumination and disengagement on adolescent neural response to reward win and loss. Participants were 122 boys and their mothers from low-income, urban backgrounds followed prospectively in a longitudinal study. The combination of high maternal rumination at child age 6 and high maternal disengagement during problem-solving at child age 10-12 was associated with lower anterior cingulate response to winning reward at age 20, but unrelated to neural response to losing reward. Lower anterior cingulate response to winning reward was associated with fewer anxiety symptoms during late adulthood. Findings suggest that maternal rumination occurring within the context of maternal disengagement during challenging experiences may be related to offspring blunted engagement during positive events. Helping highly ruminative mothers to restructure repetitive negative thoughts and to develop context-appropriate problem-solving behaviors may be important for promoting offspring affective development. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  16. Self-control of chaos in neural circuits with plastic electrical synapses

    Science.gov (United States)

    Zhigulin, V. P.; Rabinovich, M. I.

    2004-10-01

    Two kinds of connections are known to exist in neural circuits: electrical (also called gap junctions) and chemical. Whereas chemical synapses are known to be plastic (i. e., modifiable), but slow, electrical transmission through gap junctions is not modifiable, but is very fast. We suggest the new artificial synapse that combines the best properties of both: the fast reaction of a gap junction and the plasticity of a chemical synapse. Such a plastic electrical synapse can be used in hybrid neural circuits and for the development of neural prosthetics, i.e., implanted devices that can interact with the real nervous system. Based on the computer modelling we show that such a plastic electrical synapse regularizes chaos in the minimal neural circuit consisting of two chaotic bursting neurons.

  17. Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task.

    NARCIS (Netherlands)

    van Duuren, E.; Escamez, F.A.N.; Joosten, R.N.J.M.A.; Visser, R.; Mulder, A.B.; Pennartz, C.M.A.

    2007-01-01

    The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural

  18. An Implantable Mixed Analog/Digital Neural Stimulator Circuit

    DEFF Research Database (Denmark)

    Gudnason, Gunnar; Bruun, Erik; Haugland, Morten

    1999-01-01

    This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation. The chip performs all the signal processing required in an implanted neural stimulator. The power and signal transmission to the stimulator is carried out via an inductive link. From the signals...

  19. Anomalous neural circuit function in schizophrenia during a virtual Morris water task.

    Science.gov (United States)

    Folley, Bradley S; Astur, Robert; Jagannathan, Kanchana; Calhoun, Vince D; Pearlson, Godfrey D

    2010-02-15

    Previous studies have reported learning and navigation impairments in schizophrenia patients during virtual reality allocentric learning tasks. The neural bases of these deficits have not been explored using functional MRI despite well-explored anatomic characterization of these paradigms in non-human animals. Our objective was to characterize the differential distributed neural circuits involved in virtual Morris water task performance using independent component analysis (ICA) in schizophrenia patients and controls. Additionally, we present behavioral data in order to derive relationships between brain function and performance, and we have included a general linear model-based analysis in order to exemplify the incremental and differential results afforded by ICA. Thirty-four individuals with schizophrenia and twenty-eight healthy controls underwent fMRI scanning during a block design virtual Morris water task using hidden and visible platform conditions. Independent components analysis was used to deconstruct neural contributions to hidden and visible platform conditions for patients and controls. We also examined performance variables, voxel-based morphometry and hippocampal subparcellation, and regional BOLD signal variation. Independent component analysis identified five neural circuits. Mesial temporal lobe regions, including the hippocampus, were consistently task-related across conditions and groups. Frontal, striatal, and parietal circuits were recruited preferentially during the visible condition for patients, while frontal and temporal lobe regions were more saliently recruited by controls during the hidden platform condition. Gray matter concentrations and BOLD signal in hippocampal subregions were associated with task performance in controls but not patients. Patients exhibited impaired performance on the hidden and visible conditions of the task, related to negative symptom severity. While controls showed coupling between neural circuits, regional

  20. Neural correlates of reward processing in healthy siblings of patients with schizophrenia

    NARCIS (Netherlands)

    Hanssen, Esther; van der Velde, Jorien; Gromann, Paula M.; Shergill, Sukhi S.; de Haan, Lieuwe; Bruggeman, Richard; Krabbendam, Lydia; Aleman, Andre; van Atteveldt, Nienke

    2015-01-01

    Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be

  1. Nonlinear resonances and multi-stability in simple neural circuits

    Science.gov (United States)

    Alonso, Leandro M.

    2017-01-01

    This article describes a numerical procedure designed to tune the parameters of periodically driven dynamical systems to a state in which they exhibit rich dynamical behavior. This is achieved by maximizing the diversity of subharmonic solutions available to the system within a range of the parameters that define the driving. The procedure is applied to a problem of interest in computational neuroscience: a circuit composed of two interacting populations of neurons under external periodic forcing. Depending on the parameters that define the circuit, such as the weights of the connections between the populations, the response of the circuit to the driving can be strikingly rich and diverse. The procedure is employed to find circuits that, when driven by external input, exhibit multiple stable patterns of periodic activity organized in complex tuning diagrams and signatures of low dimensional chaos.

  2. A Reward-Based Behavioral Platform to Measure Neural Activity during Head-Fixed Behavior

    Directory of Open Access Journals (Sweden)

    Andrew H. Micallef

    2017-05-01

    Full Text Available Understanding the neural computations that contribute to behavior requires recording from neurons while an animal is behaving. This is not an easy task as most subcellular recording techniques require absolute head stability. The Go/No-Go sensory task is a powerful decision-driven task that enables an animal to report a binary decision during head-fixation. Here we discuss how to set up an Ardunio and Python based platform system to control a Go/No-Go sensory behavior paradigm. Using an Arduino micro-controller and Python-based custom written program, a reward can be delivered to the animal depending on the decision reported. We discuss the various components required to build the behavioral apparatus that can control and report such a sensory stimulus paradigm. This system enables the end user to control the behavioral testing in real-time and therefore it provides a strong custom-made platform for probing the neural basis of behavior.

  3. Matching Behavior as a Tradeoff Between Reward Maximization and Demands on Neural Computation [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jan Kubanek

    2015-10-01

    Full Text Available When faced with a choice, humans and animals commonly distribute their behavior in proportion to the frequency of payoff of each option. Such behavior is referred to as matching and has been captured by the matching law. However, matching is not a general law of economic choice. Matching in its strict sense seems to be specifically observed in tasks whose properties make matching an optimal or a near-optimal strategy. We engaged monkeys in a foraging task in which matching was not the optimal strategy. Over-matching the proportions of the mean offered reward magnitudes would yield more reward than matching, yet, surprisingly, the animals almost exactly matched them. To gain insight into this phenomenon, we modeled the animals' decision-making using a mechanistic model. The model accounted for the animals' macroscopic and microscopic choice behavior. When the models' three parameters were not constrained to mimic the monkeys' behavior, the model over-matched the reward proportions and in doing so, harvested substantially more reward than the monkeys. This optimized model revealed a marked bottleneck in the monkeys' choice function that compares the value of the two options. The model featured a very steep value comparison function relative to that of the monkeys. The steepness of the value comparison function had a profound effect on the earned reward and on the level of matching. We implemented this value comparison function through responses of simulated biological neurons. We found that due to the presence of neural noise, steepening the value comparison requires an exponential increase in the number of value-coding neurons. Matching may be a compromise between harvesting satisfactory reward and the high demands placed by neural noise on optimal neural computation.

  4. Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males.

    Science.gov (United States)

    Macoveanu, Julian; Fisher, Patrick M; Haahr, Mette E; Frokjaer, Vibe G; Knudsen, Gitte M; Siebner, Hartwig R

    2014-10-01

    Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT) system, yet little is known about the functional effects of prolonged serotonin reuptake inhibition in healthy individuals. Here we used functional MRI (fMRI) to investigate how a three-week fluoxetine intervention influences neural activity related to risk taking and reward processing. Employing a double-blinded parallel-group design, 29 healthy young males were randomly assigned to receive 3 weeks of a daily dose of 40 mg fluoxetine or placebo. Participants underwent task-related fMRI prior to and after the three-week intervention while performing a card gambling task. The task required participants to choose between two decks of cards. Choices were associated with different risk levels and potential reward magnitudes. Relative to placebo, the SSRI intervention did not alter individual risk-choice preferences, but modified neural activity during decision-making and reward processing: During the choice phase, SSRI reduced the neural response to increasing risk in lateral orbitofrontal cortex, a key structure for value-based decision-making. During the outcome phase, a midbrain region showed an independent decrease in the responsiveness to rewarding outcomes. This midbrain cluster included the raphe nuclei from which serotonergic modulatory projections originate to both cortical and subcortical regions. The findings corroborate the involvement of the normally functioning 5HT-system in decision-making under risk and processing of monetary rewards. The data suggest that prolonged SSRI treatment might reduce emotional engagement by reducing the impact of risk during decision-making or the impact of reward during outcome evaluation. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence.

    Science.gov (United States)

    Murphy, Anna; Nestor, Liam J; McGonigle, John; Paterson, Louise; Boyapati, Venkataramana; Ersche, Karen D; Flechais, Remy; Kuchibatla, Shankar; Metastasio, Antonio; Orban, Csaba; Passetti, Filippo; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor; Robbins, Trevor W; Lingford-Hughes, Anne; Nutt, David J; Deakin, John Fw; Elliott, Rebecca

    2017-04-01

    Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT). A double-blind, placebo-controlled, crossover design approach was used in abstinent alcohol dependent, abstinent poly-drug dependent and healthy control volunteers. For the MIDT, there was evidence of blunted ventral striatal response to reward in the poly-drug-dependent group under placebo. GSK598809 normalized ventral striatal reward response and enhanced response in the DRD3-rich regions of the ventral pallidum and substantia nigra. Exploratory investigations suggested that the effects of GSK598809 were mainly driven by those with primary dependence on alcohol but not on opiates. Taken together, these findings suggest that GSK598809 may remediate reward deficits in substance dependence. For the GNGT, enhanced response in the inferior frontal cortex of the poly-drug group was found. However, there were no effects of GSK598809 on the neural network underlying response inhibition nor were there any behavioral drug effects on response inhibition. GSK598809 modulated the neural network underlying reward anticipation but not response inhibition, suggesting that DRD3 antagonists may restore reward deficits in addiction.

  6. The Vite Model: A Neural Command Circuit for Generating Arm and Articulator Trajectories,

    Science.gov (United States)

    1988-03-01

    associative map, looking at an object can activate a TPC of the hand-arm system, as Piaget (1963) noted. Then a VITE circuit can translate this latter TPC...two ways: by comparing trajectories of the neural circuit’s output stage with actual arm trajectories, and by checking for the existence of the...in precentral motor cortex could be analysed as an in vivo analogue of model DV stage neurons. Additional physiological support for the VITE model

  7. The neurobiology of sound-specific auditory plasticity: a core neural circuit.

    Science.gov (United States)

    Xiong, Ying; Zhang, Yonghai; Yan, Jun

    2009-09-01

    Auditory learning or experience induces large-scale neural plasticity in not only the auditory cortex but also in the auditory thalamus and midbrain. Such plasticity is guided by acquired sound (sound-specific auditory plasticity). The mechanisms involved in this process have been studied from various approaches and support the presence of a core neural circuit consisting of a subcortico-cortico-subcortical tonotopic loop supplemented by neuromodulatory (e.g., cholinergic) inputs. This circuit has three key functions essential for establishing large-scale and sound-specific plasticity in the auditory cortex, auditory thalamus and auditory midbrain. They include the presence of sound information for guiding the plasticity, the communication between the cortex, thalamus and midbrain for coordinating the plastic changes and the adjustment of the circuit status for augmenting the plasticity. This review begins with an overview of sound-specific auditory plasticity in the central auditory system. It then introduces the core neural circuit which plays an essential role in inducing sound-specific auditory plasticity. Finally, the core neural circuit and its relationship to auditory learning and experience are discussed.

  8. Distributed dynamical computation in neural circuits with propagating coherent activity patterns.

    Directory of Open Access Journals (Sweden)

    Pulin Gong

    2009-12-01

    Full Text Available Activity in neural circuits is spatiotemporally organized. Its spatial organization consists of multiple, localized coherent patterns, or patchy clusters. These patterns propagate across the circuits over time. This type of collective behavior has ubiquitously been observed, both in spontaneous activity and evoked responses; its function, however, has remained unclear. We construct a spatially extended, spiking neural circuit that generates emergent spatiotemporal activity patterns, thereby capturing some of the complexities of the patterns observed empirically. We elucidate what kind of fundamental function these patterns can serve by showing how they process information. As self-sustained objects, localized coherent patterns can signal information by propagating across the neural circuit. Computational operations occur when these emergent patterns interact, or collide with each other. The ongoing behaviors of these patterns naturally embody both distributed, parallel computation and cascaded logical operations. Such distributed computations enable the system to work in an inherently flexible and efficient way. Our work leads us to propose that propagating coherent activity patterns are the underlying primitives with which neural circuits carry out distributed dynamical computation.

  9. Implantable neurotechnologies: bidirectional neural interfaces--applications and VLSI circuit implementations.

    Science.gov (United States)

    Greenwald, Elliot; Masters, Matthew R; Thakor, Nitish V

    2016-01-01

    A bidirectional neural interface is a device that transfers information into and out of the nervous system. This class of devices has potential to improve treatment and therapy in several patient populations. Progress in very large-scale integration has advanced the design of complex integrated circuits. System-on-chip devices are capable of recording neural electrical activity and altering natural activity with electrical stimulation. Often, these devices include wireless powering and telemetry functions. This review presents the state of the art of bidirectional circuits as applied to neuroprosthetic, neurorepair, and neurotherapeutic systems.

  10. Differences in neural responses to reward and punishment processing between anorexia nervosa subtypes: An fMRI study.

    Science.gov (United States)

    Murao, Ema; Sugihara, Genichi; Isobe, Masanori; Noda, Tomomi; Kawabata, Michiko; Matsukawa, Noriko; Takahashi, Hidehiko; Murai, Toshiya; Noma, Shun'ichi

    2017-09-01

    Anorexia nervosa (AN) includes the restricting (AN-r) and binge-eating/purging (AN-bp) subtypes, which have been reported to differ regarding their underlying pathophysiologies as well as their behavioral patterns. However, the differences in neural mechanisms of reward systems between AN subtypes remain unclear. The aim of the present study was to explore differences in the neural processing of reward and punishment between AN subtypes. Twenty-three female patients with AN (11 AN-r and 12 AN-bp) and 20 healthy women underwent functional magnetic resonance imaging while performing a monetary incentive delay task. Whole-brain one-way analysis of variance was conducted to test between-group differences. There were significant group differences in brain activation in the rostral anterior cingulate cortex and right posterior insula during loss anticipation, with increased brain activation in the AN-bp group relative to the AN-r and healthy women groups. No significant differences were found during gain anticipation. AN-bp patients showed altered neural responses to punishment in brain regions implicated in emotional arousal. Our findings suggest that individuals with AN-bp are more sensitive to potential punishment than individuals with AN-r and healthy individuals at the neural level. The present study provides preliminary evidence that there are neurobiological differences between AN subtypes with regard to the reward system, especially punishment processing. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  11. Reward processing in anorexia nervosa.

    Science.gov (United States)

    Keating, Charlotte; Tilbrook, Alan J; Rossell, Susan L; Enticott, Peter G; Fitzgerald, Paul B

    2012-04-01

    Individuals with anorexia nervosa (AN) demonstrate a relentless engagement in behaviors aimed to reduce their weight, which leads to severe underweight status, and occasionally death. Neurobiological abnormalities, as a consequence of starvation are controversial: evidence, however, demonstrates abnormalities in the reward system of patients, and recovered individuals. Despite this, a unifying explanation for reward abnormalities observed in AN and their relevance to symptoms of the illness, remains incompletely understood. Theories explaining reward dysfunction have conventionally focused on anhedonia, describing that patients have an impaired ability to experience reward or pleasure. We review taste reward literature and propose that patients' reduced responses to conventional taste-reward tasks may reflect a fear of weight gain associated with the caloric nature of the tasks, rather than an impaired ability to experience reward. Consistent with this, we propose that patients are capable of 'liking' hedonic taste stimuli (e.g., identifying them), however, they do not 'want' or feel motivated for the stimuli in the same way that healthy controls report. Recent brain imaging data on more complex reward processing tasks provide insights into fronto-striatal neural circuit dysfunction related to altered reward processing in AN that challenges the relevance of anhedonia in explaining reward dysfunction in AN. In this way, altered activity of the anterior cingulate cortex and striatum could explain patients' pathological engagement in behaviors they consider rewarding (e.g., self-starvation) that are otherwise aversive or punishing, to those without the eating disorder. Such evidence for altered patterns of brain activity associated with reward processing tasks in patients and recovered individuals may provide important information about mechanisms underlying symptoms of AN, their future investigation, and the development of treatment approaches. Copyright © 2012

  12. DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses.

    Science.gov (United States)

    Vialou, Vincent; Robison, Alfred J; Laplant, Quincey C; Covington, Herbert E; Dietz, David M; Ohnishi, Yoshinori N; Mouzon, Ezekiell; Rush, Augustus J; Watts, Emily L; Wallace, Deanna L; Iñiguez, Sergio D; Ohnishi, Yoko H; Steiner, Michel A; Warren, Brandon L; Krishnan, Vaishnav; Bolaños, Carlos A; Neve, Rachael L; Ghose, Subroto; Berton, Olivier; Tamminga, Carol A; Nestler, Eric J

    2010-06-01

    In contrast with the many studies of stress effects on the brain, relatively little is known about the molecular mechanisms of resilience, the ability of some individuals to escape the deleterious effects of stress. We found that the transcription factor DeltaFosB mediates an essential mechanism of resilience in mice. Induction of DeltaFosB in the nucleus accumbens, an important brain reward-associated region, in response to chronic social defeat stress was both necessary and sufficient for resilience. DeltaFosB induction was also required for the standard antidepressant fluoxetine to reverse behavioral pathology induced by social defeat. DeltaFosB produced these effects through induction of the GluR2 AMPA glutamate receptor subunit, which decreased the responsiveness of nucleus accumbens neurons to glutamate, and through other synaptic proteins. Together, these findings establish a previously unknown molecular pathway underlying both resilience and antidepressant action.

  13. Neural basis of the undermining effect of monetary reward on intrinsic motivation

    National Research Council Canada - National Science Library

    Kou Murayama; Madoka Matsumoto; Keise Izuma; Kenji Matsumoto; Edward E. Smith

    2010-01-01

    Contrary to the widespread belief that people are positively motivated by reward incentives, some studies have shown that performance-based extrinsic reward can actually undermine a person's intrinsic...

  14. Deconstruction and Control of Neural Circuits in Posttraumatic Epilepsy

    Science.gov (United States)

    2017-10-01

    Holden and Frances Cho –received awards that allowed them to present their work at multiple national and international conferences. These awards...Stephanie Holden and Frances Cho – whose work focuses on this DoD-funded project, received multiple awards that allowed them to present their work at...epileptogenesis. Stephanie and Frances presented their work at multiple conferences: 8. Holden S, Paz JT (2017) Deconstruction of thalamic circuits in a mouse

  15. Neural circuit remodeling and structural plasticity in the cortex during chronic pain.

    Science.gov (United States)

    Kim, Woojin; Kim, Sun Kwang

    2016-01-01

    Damage in the periphery or spinal cord induces maladaptive plastic changes along the somatosensory nervous system from the periphery to the cortex, often leading to chronic pain. Although the role of neural circuit remodeling and structural synaptic plasticity in the 'pain matrix' cortices in chronic pain has been thought as a secondary epiphenomenon to altered nociceptive signaling in the spinal cord, progress in whole brain imaging studies on human patients and animal models has suggested a possibility that plastic changes in cortical neural circuits may actively contribute to chronic pain symptoms. Furthermore, recent development in two-photon microscopy and fluorescence labeling techniques have enabled us to longitudinally trace the structural and functional changes in local circuits, single neurons and even individual synapses in the brain of living animals. These technical advances has started to reveal that cortical structural remodeling following tissue or nerve damage could rapidly occur within days, which are temporally correlated with functional plasticity of cortical circuits as well as the development and maintenance of chronic pain behavior, thereby modifying the previous concept that it takes much longer periods (e.g. months or years). In this review, we discuss the relation of neural circuit plasticity in the 'pain matrix' cortices, such as the anterior cingulate cortex, prefrontal cortex and primary somatosensory cortex, with chronic pain. We also introduce how to apply long-term in vivo two-photon imaging approaches for the study of pathophysiological mechanisms of chronic pain.

  16. 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.

  17. Risk-taking in disorders of natural and drug rewards: neural correlates and effects of probability, valence, and magnitude.

    Science.gov (United States)

    Voon, Valerie; Morris, Laurel S; Irvine, Michael A; Ruck, Christian; Worbe, Yulia; Derbyshire, Katherine; Rankov, Vladan; Schreiber, Liana Rn; Odlaug, Brian L; Harrison, Neil A; Wood, Jonathan; Robbins, Trevor W; Bullmore, Edward T; Grant, Jon E

    2015-03-01

    Pathological behaviors toward drugs and food rewards have underlying commonalities. Risk-taking has a fourfold pattern varying as a function of probability and valence leading to the nonlinearity of probability weighting with overweighting of small probabilities and underweighting of large probabilities. Here we assess these influences on risk-taking in patients with pathological behaviors toward drug and food rewards and examine structural neural correlates of nonlinearity of probability weighting in healthy volunteers. In the anticipation of rewards, subjects with binge eating disorder show greater risk-taking, similar to substance-use disorders. Methamphetamine-dependent subjects had greater nonlinearity of probability weighting along with impaired subjective discrimination of probability and reward magnitude. Ex-smokers also had lower risk-taking to rewards compared with non-smokers. In the anticipation of losses, obesity without binge eating had a similar pattern to other substance-use disorders. Obese subjects with binge eating also have impaired discrimination of subjective value similar to that of the methamphetamine-dependent subjects. Nonlinearity of probability weighting was associated with lower gray matter volume in dorsolateral and ventromedial prefrontal cortex and orbitofrontal cortex in healthy volunteers. Our findings support a distinct subtype of binge eating disorder in obesity with similarities in risk-taking in the reward domain to substance use disorders. The results dovetail with the current approach of defining mechanistically based dimensional approaches rather than categorical approaches to psychiatric disorders. The relationship to risk probability and valence may underlie the propensity toward pathological behaviors toward different types of rewards.

  18. The generation effect: activating broad neural circuits during memory encoding.

    Science.gov (United States)

    Rosner, Zachary A; Elman, Jeremy A; Shimamura, Arthur P

    2013-01-01

    The generation effect is a robust memory phenomenon in which actively producing material during encoding acts to improve later memory performance. In a functional magnetic resonance imaging (fMRI) analysis, we explored the neural basis of this effect. During encoding, participants generated synonyms from word-fragment cues (e.g., GARBAGE-W_ST_) or read other synonym pairs (e.g., GARBAGE-WASTE). Compared to simply reading target words, generating target words significantly improved later recognition memory performance. During encoding, this benefit was associated with a broad neural network that involved both prefrontal (inferior frontal gyrus, middle frontal gyrus) and posterior cortex (inferior temporal gyrus, lateral occipital cortex, parahippocampal gyrus, ventral posterior parietal cortex). These findings define the prefrontal-posterior cortical dynamics associated with the mnemonic benefits underlying the generation effect. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Operant behavior to obtain palatable food modifies neuronal plasticity in the brain reward circuit.

    Science.gov (United States)

    Guegan, Thomas; Cutando, Laura; Ayuso, Eduard; Santini, Emanuela; Fisone, Gilberto; Bosch, Fatima; Martinez, Albert; Valjent, Emmanuel; Maldonado, Rafael; Martin, Miquel

    2013-02-01

    Palatability enhances food intake by hedonic mechanisms that prevail over caloric necessities. Different studies have demonstrated the role of endogenous cannabinoids in the mesocorticolimbic system in controlling food hedonic value and consumption. We hypothesize that the endogenous cannabinoid system could also be involved in the development of food-induced behavioral alterations, such as food-seeking and binge-eating, by a mechanism that requires neuroplastic changes in the brain reward pathway. For this purpose, we evaluated the role of the CB1 cannabinoid receptor (CB1-R) in the behavioral and neuroplastic changes induced by operant training for standard, highly caloric or highly palatable isocaloric food using different genetics, viral and pharmacological approaches. Neuroplasticity was evaluated by measuring changes in dendritic spine density in neurons previously labeled with the dye DiI. Only operant training to obtain highly palatable isocaloric food induced neuroplastic changes in neurons of the nucleus accumbens shell and prefrontal cortex that were associated to changes in food-seeking behavior. These behavioral and neuroplastic modifications induced by highly palatable isocaloric food were dependent on the activity of the CB1-R. Neuroplastic changes induced by highly palatable isocaloric food are similar to those produced by some drugs of abuse and may be crucial in the alteration of food-seeking behavior leading to overweight and obesity. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

  20. Priming Neural Circuits to Modulate Spinal Reflex Excitability

    OpenAIRE

    Estes, Stephen P.; Iddings, Jennifer A.; Field-Fote, Edelle C.

    2017-01-01

    While priming is most often thought of as a strategy for modulating neural excitability to facilitate voluntary motor control, priming stimulation can also be utilized to target spinal reflex excitability. In this application, priming can be used to modulate the involuntary motor output that often follows central nervous system injury. Individuals with spinal cord injury (SCI) often experience spasticity, for which antispasmodic medications are the most common treatment. Physical therapeutic/...

  1. 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.

  2. 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.

  3. A neural space vector fault location for parallel double-circuit distribution lines

    Energy Technology Data Exchange (ETDEWEB)

    Sousa Martins, L.; Martins, J.F.; Fernao Pires, V. [Politecnico de Setubal (Portugal). Escola Sup. Tecnol.; Alegria, C.M. [Instituto Superior Tecnico, Lisbon (Portugal)

    2005-03-01

    A new approach to fault location for parallel double-circuit distribution power lines is presented. This approach uses the Clark-Concordia transformation and an artificial neural network based learning algorithm. The {alpha}, {beta}, 0 components of double line currents resulting from the Clarke-Concordia transformation are used to characterize different states of the system. The neural network is trained to map the non-linear relationship existing between fault location and characteristic eigenvalue. The proposed approach is able to identify and to locate different types of faults such as: phase-to-earth, phase-to-phase, two-phase-to-earth and three-phase. Using the eigenvalue as neural network inputs the proposed algorithm locates the fault distance. Results are presented which show the effectiveness of the proposed algorithm for a correct fault location on a parallel double-circuit distribution line. (author)

  4. Dopamine Signaling in reward-related behaviors

    Directory of Open Access Journals (Sweden)

    Ja-Hyun eBaik

    2013-10-01

    Full Text Available Dopamine (DA regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DAmesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural rewards such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.

  5. Reward Selectively Modulates the Lingering Neural Representation of Recently Attended Objects in Natural Scenes.

    Science.gov (United States)

    Hickey, Clayton; Peelen, Marius V

    2017-08-02

    Theories of reinforcement learning and approach behavior suggest that reward can increase the perceptual salience of environmental stimuli, ensuring that potential predictors of outcome are noticed in the future. However, outcome commonly follows visual processing of the environment, occurring even when potential reward cues have long disappeared. How can reward feedback retroactively cause now-absent stimuli to become attention-drawing in the future? One possibility is that reward and attention interact to prime lingering visual representations of attended stimuli that sustain through the interval separating stimulus and outcome. Here, we test this idea using multivariate pattern analysis of fMRI data collected from male and female humans. While in the scanner, participants searched for examples of target categories in briefly presented pictures of cityscapes and landscapes. Correct task performance was followed by reward feedback that could randomly have either high or low magnitude. Analysis showed that high-magnitude reward feedback boosted the lingering representation of target categories while reducing the representation of nontarget categories. The magnitude of this effect in each participant predicted the behavioral impact of reward on search performance in subsequent trials. Other analyses show that sensitivity to reward-as expressed in a personality questionnaire and in reactivity to reward feedback in the dopaminergic midbrain-predicted reward-elicited variance in lingering target and nontarget representations. Credit for rewarding outcome thus appears to be assigned to the target representation, causing the visual system to become sensitized for similar objects in the future. SIGNIFICANCE STATEMENT How do reward-predictive visual stimuli become salient and attention-drawing? In the real world, reward cues precede outcome and reward is commonly received long after potential predictors have disappeared. How can the representation of environmental stimuli

  6. 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.

  7. Ontogeny of neural circuits underlying spatial memory in the rat

    Directory of Open Access Journals (Sweden)

    James Alexander Ainge

    2012-03-01

    Full Text Available Spatial memory is a well characterised psychological function in both humans and rodents. The combined computations of a network of systems including place cells in the hippocampus, grid cells in the medial entorhinal cortex and head direction cells found in numerous structures in the brain have been suggested to form the neural instantiation of the cognitive map as first described by Tolman in 1948. However, while our understanding of the neural mechanisms underlying spatial representations in adults is relatively sophisticated, we know substantially less about how this network develops in young animals. In this article we review studies examining the developmental timescale that these systems follow. Electrophysiological recordings from very young rats show that directional information is at adult levels at the outset of navigational experience. The systems supporting allocentric memory, however, take longer to mature. This is consistent with behavioural studies of young rats which show that spatial memory based on head direction develops very early but that allocentric spatial memory takes longer to mature. We go on to report new data demonstrating that memory for associations between objects and their spatial locations is slower to develop than memory for objects alone. This is again consistent with previous reports suggesting that adult like spatial representations have a protracted development in rats and also suggests that the systems involved in processing non-spatial stimuli come online earlier.

  8. Spatiotemporal imaging of glutamate-induced biophotonic activities and transmission in neural circuits.

    Directory of Open Access Journals (Sweden)

    Rendong Tang

    Full Text Available The processing of neural information in neural circuits plays key roles in neural functions. Biophotons, also called ultra-weak photon emissions (UPE, may play potential roles in neural signal transmission, contributing to the understanding of the high functions of nervous system such as vision, learning and memory, cognition and consciousness. However, the experimental analysis of biophotonic activities (emissions in neural circuits has been hampered due to technical limitations. Here by developing and optimizing an in vitro biophoton imaging method, we characterize the spatiotemporal biophotonic activities and transmission in mouse brain slices. We show that the long-lasting application of glutamate to coronal brain slices produces a gradual and significant increase of biophotonic activities and achieves the maximal effect within approximately 90 min, which then lasts for a relatively long time (>200 min. The initiation and/or maintenance of biophotonic activities by glutamate can be significantly blocked by oxygen and glucose deprivation, together with the application of a cytochrome c oxidase inhibitor (sodium azide, but only partly by an action potential inhibitor (TTX, an anesthetic (procaine, or the removal of intracellular and extracellular Ca(2+. We also show that the detected biophotonic activities in the corpus callosum and thalamus in sagittal brain slices mostly originate from axons or axonal terminals of cortical projection neurons, and that the hyperphosphorylation of microtubule-associated protein tau leads to a significant decrease of biophotonic activities in these two areas. Furthermore, the application of glutamate in the hippocampal dentate gyrus results in increased biophotonic activities in its intrahippocampal projection areas. These results suggest that the glutamate-induced biophotonic activities reflect biophotonic transmission along the axons and in neural circuits, which may be a new mechanism for the processing of

  9. How Do Efficient Coding Strategies Depend on Origins of Noise in Neural Circuits?

    Science.gov (United States)

    Brinkman, Braden A W; Weber, Alison I; Rieke, Fred; Shea-Brown, Eric

    2016-10-01

    Neural circuits reliably encode and transmit signals despite the presence of noise at multiple stages of processing. The efficient coding hypothesis, a guiding principle in computational neuroscience, suggests that a neuron or population of neurons allocates its limited range of responses as efficiently as possible to best encode inputs while mitigating the effects of noise. Previous work on this question relies on specific assumptions about where noise enters a circuit, limiting the generality of the resulting conclusions. Here we systematically investigate how noise introduced at different stages of neural processing impacts optimal coding strategies. Using simulations and a flexible analytical approach, we show how these strategies depend on the strength of each noise source, revealing under what conditions the different noise sources have competing or complementary effects. We draw two primary conclusions: (1) differences in encoding strategies between sensory systems-or even adaptational changes in encoding properties within a given system-may be produced by changes in the structure or location of neural noise, and (2) characterization of both circuit nonlinearities as well as noise are necessary to evaluate whether a circuit is performing efficiently.

  10. How Do Efficient Coding Strategies Depend on Origins of Noise in Neural Circuits?

    Directory of Open Access Journals (Sweden)

    Braden A W Brinkman

    2016-10-01

    Full Text Available Neural circuits reliably encode and transmit signals despite the presence of noise at multiple stages of processing. The efficient coding hypothesis, a guiding principle in computational neuroscience, suggests that a neuron or population of neurons allocates its limited range of responses as efficiently as possible to best encode inputs while mitigating the effects of noise. Previous work on this question relies on specific assumptions about where noise enters a circuit, limiting the generality of the resulting conclusions. Here we systematically investigate how noise introduced at different stages of neural processing impacts optimal coding strategies. Using simulations and a flexible analytical approach, we show how these strategies depend on the strength of each noise source, revealing under what conditions the different noise sources have competing or complementary effects. We draw two primary conclusions: (1 differences in encoding strategies between sensory systems-or even adaptational changes in encoding properties within a given system-may be produced by changes in the structure or location of neural noise, and (2 characterization of both circuit nonlinearities as well as noise are necessary to evaluate whether a circuit is performing efficiently.

  11. Common and distinct neural correlates of personal and vicarious reward: A quantitative meta-analysis.

    Science.gov (United States)

    Morelli, Sylvia A; Sacchet, Matthew D; Zaki, Jamil

    2015-05-15

    Individuals experience reward not only when directly receiving positive outcomes (e.g., food or money), but also when observing others receive such outcomes. This latter phenomenon, known as vicarious reward, is a perennial topic of interest among psychologists and economists. More recently, neuroscientists have begun exploring the neuroanatomy underlying vicarious reward. Here we present a quantitative whole-brain meta-analysis of this emerging literature. We identified 25 functional neuroimaging studies that included contrasts between vicarious reward and a neutral control, and subjected these contrasts to an activation likelihood estimate (ALE) meta-analysis. This analysis revealed a consistent pattern of activation across studies, spanning structures typically associated with the computation of value (especially ventromedial prefrontal cortex) and mentalizing (including dorsomedial prefrontal cortex and superior temporal sulcus). We further quantitatively compared this activation pattern to activation foci from a previous meta-analysis of personal reward. Conjunction analyses yielded overlapping VMPFC activity in response to personal and vicarious reward. Contrast analyses identified preferential engagement of the nucleus accumbens in response to personal as compared to vicarious reward, and in mentalizing-related structures in response to vicarious as compared to personal reward. These data shed light on the common and unique components of the reward that individuals experience directly and through their social connections. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. A simple structure wavelet transform circuit employing function link neural networks and SI filters

    Science.gov (United States)

    Mu, Li; Yigang, He

    2016-12-01

    Signal processing by means of analog circuits offers advantages from a power consumption viewpoint. Implementing wavelet transform (WT) using analog circuits is of great interest when low-power consumption becomes an important issue. In this article, a novel simple structure WT circuit in analog domain is presented by employing functional link neural network (FLNN) and switched-current (SI) filters. First, the wavelet base is approximated using FLNN algorithms for giving a filter transfer function that is suitable for simple structure WT circuit implementation. Next, the WT circuit is constructed with the wavelet filter bank, whose impulse response is the approximated wavelet and its dilations. The filter design that follows is based on a follow-the-leader feedback (FLF) structure with multiple output bilinear SI integrators and current mirrors as the main building blocks. SI filter is well suited for this application since the dilation constant across different scales of the transform can be precisely implemented and controlled by the clock frequency of the circuit with the same system architecture. Finally, to illustrate the design procedure, a seventh-order FLNN-approximated Gaussian wavelet is implemented as an example. Simulations have successfully verified that the designed simple structure WT circuit has low sensitivity, low-power consumption and litter effect to the imperfections.

  13. PCSIM: A Parallel Simulation Environment for Neural Circuits Fully Integrated with Python

    Science.gov (United States)

    Pecevski, Dejan; Natschläger, Thomas; Schuch, Klaus

    2008-01-01

    The Parallel Circuit SIMulator (PCSIM) is a software package for simulation of neural circuits. It is primarily designed for distributed simulation of large scale networks of spiking point neurons. Although its computational core is written in C++, PCSIM's primary interface is implemented in the Python programming language, which is a powerful programming environment and allows the user to easily integrate the neural circuit simulator with data analysis and visualization tools to manage the full neural modeling life cycle. The main focus of this paper is to describe PCSIM's full integration into Python and the benefits thereof. In particular we will investigate how the automatically generated bidirectional interface and PCSIM's object-oriented modular framework enable the user to adopt a hybrid modeling approach: using and extending PCSIM's functionality either employing pure Python or C++ and thus combining the advantages of both worlds. Furthermore, we describe several supplementary PCSIM packages written in pure Python and tailored towards setting up and analyzing neural simulations. PMID:19543450

  14. Longitudinal Associations Between Preschool Disruptive Mood Dysregulation Disorder Symptoms and Neural Reactivity to Monetary Reward During Preadolescence

    Science.gov (United States)

    Dougherty, Lea R.; Kujawa, Autumn; Hajcak, Greg; Carlson, Gabrielle A.; Klein, Daniel N.

    2016-01-01

    Abstract Objective: Reward-processing abnormalities are thought to be a key feature of various psychiatric disorders and may also play a role in disruptive mood dysregulation disorder (DMDD), a new diagnosis in DSM-5. In the current study, we used event-related potentials (ERP) sensitive to monetary gains (i.e., the reward positivity [RewP]) and losses (i.e., the N200) to examine associations between symptoms of DMDD during early childhood and later reward processing during preadolescence. Methods: To assess early emerging DMDD symptoms in a large longitudinal community sample (n=373) of 3-year old children, we administered a diagnostic interview, Preschool Age Psychiatric Assessment (PAPA) with parents. At a later assessment, ∼6 years later, children completed a monetary reward task while an electroencephalogram (EEG) was recorded. Children's lifetime history of psychopathology was also assessed at that time using Kiddie-Schedule of Affective Disorders and Schizophrenia (K-SADS) with the child and parent. Results: Multiple regression analyses revealed that age 3 DMDD symptoms predicted an enhanced RewP to monetary rewards in preadolescence. This association is independent of demographics and lifetime history of symptoms of depression, any anxiety disorder, attention-deficit disorder, oppositional defiant disorder, or conduct disorder Conclusions: Early manifestations of DMDD in children as young as 3 years old predicted enhanced reward processing later in development. These findings add to the growing corpus of literature on the pathophysiology of DMDD, and underscore the predictive validity of preschool DMDD on a neural level. PMID:26771832

  15. Massively parallel neural circuits for stereoscopic color vision: encoding, decoding and identification.

    Science.gov (United States)

    Lazar, Aurel A; Slutskiy, Yevgeniy B; Zhou, Yiyin

    2015-03-01

    Past work demonstrated how monochromatic visual stimuli could be faithfully encoded and decoded under Nyquist-type rate conditions. Color visual stimuli were then traditionally encoded and decoded in multiple separate monochromatic channels. The brain, however, appears to mix information about color channels at the earliest stages of the visual system, including the retina itself. If information about color is mixed and encoded by a common pool of neurons, how can colors be demixed and perceived? We present Color Video Time Encoding Machines (Color Video TEMs) for encoding color visual stimuli that take into account a variety of color representations within a single neural circuit. We then derive a Color Video Time Decoding Machine (Color Video TDM) algorithm for color demixing and reconstruction of color visual scenes from spikes produced by a population of visual neurons. In addition, we formulate Color Video Channel Identification Machines (Color Video CIMs) for functionally identifying color visual processing performed by a spiking neural circuit. Furthermore, we derive a duality between TDMs and CIMs that unifies the two and leads to a general theory of neural information representation for stereoscopic color vision. We provide examples demonstrating that a massively parallel color visual neural circuit can be first identified with arbitrary precision and its spike trains can be subsequently used to reconstruct the encoded stimuli. We argue that evaluation of the functional identification methodology can be effectively and intuitively performed in the stimulus space. In this space, a signal reconstructed from spike trains generated by the identified neural circuit can be compared to the original stimulus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. In search of the neural circuits of intrinsic motivation

    Directory of Open Access Journals (Sweden)

    Frederic Kaplan

    2007-10-01

    Full Text Available Children seem to acquire new know-how in a continuous and open-ended manner. In this paper, we hypothesize that an intrinsic motivation to progress in learning is at the origins of the remarkable structure of children's developmental trajectories. In this view, children engage in exploratory and playful activities for their own sake, not as steps toward other extrinsic goals. The central hypothesis of this paper is that intrinsically motivating activities correspond to expected decrease in prediction error. This motivation system pushes the infant to avoid both predictable and unpredictable situations in order to focus on the ones that are expected to maximize progress in learning. Based on a computational model and a series of robotic experiments, we show how this principle can lead to organized sequences of behavior of increasing complexity characteristic of several behavioral and developmental patterns observed in humans. We then discuss the putative circuitry underlying such an intrinsic motivation system in the brain and formulate two novel hypotheses. The first one is that tonic dopamine acts as a learning progress signal. The second is that this progress signal is directly computed through a hierarchy of microcortical circuits that act both as prediction and metaprediction systems.

  17. What motivates adolescents? Neural responses to rewards and their influence on adolescents' risk taking, learning, and cognitive control.

    Science.gov (United States)

    van Duijvenvoorde, Anna C K; Peters, Sabine; Braams, Barbara R; Crone, Eveline A

    2016-11-01

    Adolescence is characterized by pronounced changes in motivated behavior, during which emphasis on potential rewards may result in an increased tendency to approach things that are novel and bring potential for positive reinforcement. While this may result in risky and health-endangering behavior, it may also lead to positive consequences, such as behavioral flexibility and greater learning. In this review we will discuss both the maladaptive and adaptive properties of heightened reward-sensitivity in adolescents by reviewing recent cognitive neuroscience findings in relation to behavioral outcomes. First, we identify brain regions involved in processing rewards in adults and adolescents. Second, we discuss how functional changes in reward-related brain activity during adolescence are related to two behavioral domains: risk taking and cognitive control. Finally, we conclude that progress lies in new levels of explanation by further integration of neural results with behavioral theories and computational models. In addition, we highlight that longitudinal measures, and a better conceptualization of adolescence and environmental determinants, are of crucial importance for understanding positive and negative developmental trajectories. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Neural activity related to the processing of increasing monetary reward in smokers and nonsmokers

    NARCIS (Netherlands)

    Martin-Soelch, C; Missimer, J; Leenders, KL; Schultz, W

    This study investigated the processing of increasing monetary reward in nonsmoking and smoking subjects. The choice of the subject populations has been motivated by the observation of differences between nonsmokers and smokers in response to rewarding stimuli in a previous study. Subjects performed

  19. Neural signature of food reward processing in bulimic-type eating disorders.

    Science.gov (United States)

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

    2016-09-01

    Clinical observations and similarities to addiction suggest heightened reward sensitivity to food in patients with bulimic-type eating (BTE) disorders. Therefore, we investigated the expectation and receipt of food reward compared with monetary reward in patients with BTE. Fifty-six patients with BTE (27 patients with binge eating disorder and 29 with bulimia nervosa) and 55 matched healthy control participants underwent event-related functional magnetic resonance imaging while performing both food and monetary incentive delay tasks. BTE patients exhibited reduced brain activation in the posterior cingulate cortex during the expectation of food and increased activity in the medial orbitofrontal cortex, anterior medial prefrontal cortex and posterior cingulate cortex during the receipt of food reward. These findings were relevant to food because we found no significant group differences related to monetary reward. In the patients, higher brain activity in the medial orbitofrontal cortex during the receipt of food reward was related to higher levels of trait food craving and external eating. BTE patients exhibited increased hedonic processing during the receipt of food reward. These findings corroborate the notion that an altered responsiveness of the reward network to food stimuli is associated with BTE. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. The effects of psychotherapy on neural responses to rewards in major depression.

    Science.gov (United States)

    Dichter, Gabriel S; Felder, Jennifer N; Petty, Christopher; Bizzell, Joshua; Ernst, Monique; Smoski, Moria J

    2009-11-01

    Unipolar major depressive disorder (MDD) is characterized by anomalous neurobiological responses to pleasant stimuli, a pattern that may be linked to symptoms of anhedonia. However, the potential for psychotherapy to normalize neurobiological responses to pleasant stimuli has not been evaluated. Twelve adults with and 15 adults without MDD participated in two identical functional magnetic resonance imaging scans that used a Wheel of Fortune task. Between scans, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Seventy-five percent of adults with MDD were treatment responders, achieving post-treatment Hamilton Rating Scale for Depression score of six or below. Relative to changes in brain function in the matched nondepressed group, psychotherapy resulted in functional changes in structures that mediate responses to rewards, including the paracingulate gyrus during reward selection, the right caudate nucleus (i.e., the dorsal striatum), during reward anticipation, and the paracingulate and orbital frontal gyri during reward feedback. There was no effect of diagnostic status or psychotherapy on in-scanner task-related behavioral responses. Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors, results in improved functioning of unique reward structures during different temporal phases of responses to pleasurable stimuli, including the dorsal striatum during reward anticipation.

  1. Neural correlates of reward processing in healthy siblings of patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Esther eHanssen

    2015-09-01

    Full Text Available Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ may be driven by dysfunctional reward processing (RP. RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be related to SZ. Studies in patients with SZ have found less activation in the ventral striatum (VS during anticipation of reward, but these findings do not provide information on effect of the genetic load on reward processing. Therefore, this study investigated RP in healthy first-degree relatives of SZ patients. The sample consisted of 94 healthy siblings of SZ patients and 57 healthy controls. Participants completed a classic RP task, the Monetary Incentive Delay task, during functional magnetic resonance imaging (fMRI. As expected, there were no behavioral differences between groups. In contrast to our expectations, we found no differences in any of the anticipatory reward related brain areas (region of interest analyses. Whole-brain analyses did reveal group differences during both reward anticipation and reward consumption; during reward anticipation siblings showed less deactivation in the insula, posterior cingulate cortex (PCC and medial frontal gyrus (MFG than controls. During reward consumption siblings showed less deactivation in the PCC and the right MFG compared to controls and activation in contrast to deactivation in controls in the precuneus and the left MFG. Exclusively in siblings, MFG activity correlated positively with subclinical negative symptoms. These regions are typically associated with the default mode network (DMN, which normally shows decreases in activation during task-related cognitive processes. Thus, in contrast to prior literature in patients with SZ, the results do not point to altered brain activity in classical RP brain areas, such as the VS. However, the weaker deactivation found outside the reward-related network in

  2. 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.

  3. Nanowire electrodes for high-density stimulation and measurement of neural circuits

    Directory of Open Access Journals (Sweden)

    Jacob T. Robinson

    2013-03-01

    Full Text Available Brain-machine interfaces (BMIs that can precisely monitor and control neural activity will likely require new hardware with improved resolution and specificity. New nanofabricated electrodes with feature sizes and densities comparable to neural circuits may lead to such improvements. In this perspective, we review the recent development of vertical nanowire (NW electrodes that could provide highly parallel single-cell recording and stimulation for future BMIs. We compare the advantages of these devices and discuss some of the technical challenges that must be overcome for this technology to become a platform for next-generation closed-loop BMIs.

  4. Neuromodulation of the neural circuits controlling the lower urinary tract.

    Science.gov (United States)

    Gad, Parag N; Roy, Roland R; Zhong, Hui; Gerasimenko, Yury P; Taccola, Giuliano; Edgerton, V Reggie

    2016-11-01

    The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. Copyright © 2016. Published by Elsevier Inc.

  5. [Progress in activity-dependent structural plasticity of neural circuits in cortex].

    Science.gov (United States)

    Rao, Xiao-Ping; Xu, Zhi-Xiang; Xu, Fu-Qiang

    2012-10-01

    Neural circuits of mammalian cerebral cortex have exhibited amazing abilities of structural and functional plasticity in development, learning and memory, neurological and psychiatric diseases. With the new imaging techniques and the application of molecular biology methods, observation neural circuits' structural dynamics within the cortex in vivo at the cellular and synaptic level was possible, so there were many great progresses in the field of the activity-dependent structural plasticity over the past decade. This paper reviewed some of the aspects of the experimental results, focused on the characteristics of dendritic structural plasticity in individual growth and development, rich environment, sensory deprivation, and pathological conditions, as well as learning and memory, especially the dynamics of dendritic spines on morphology and quantity; after that, we introduced axonal structural plasticity, the molecular and cellular mechanisms of structural plasticity, and proposed some future problems to be solved at last.

  6. Automated cell-specific laser detection and ablation of neural circuits in neonatal brain tissue

    Science.gov (United States)

    Wang, Xueying; Hayes, John A; Picardo, Maria Cristina D; Del Negro, Christopher A

    2013-01-01

    A key feature of neurodegenerative disease is the pathological loss of neurons that participate in generating behaviour. To investigate network properties of neural circuits and provide a complementary tool to study neurodegeneration in vitro or in situ, we developed an automated cell-specific laser detection and ablation system. The instrument consists of a two-photon and visible-wavelength confocal imaging setup, controlled by executive software, that identifies neurons in preparations based on genetically encoded fluorescent proteins or Ca2+ imaging, and then sequentially ablates cell targets while monitoring network function concurrently. Pathological changes in network function can be directly attributed to ablated cells, which are logged in real time. Here, we investigated brainstem respiratory circuits to demonstrate single-cell precision in ablation during physiological network activity, but the technique could be applied to interrogate network properties in neural systems that retain network functionality in reduced preparations in vitro or in situ. PMID:23440965

  7. A decision-making model based on a spiking neural circuit and synaptic plasticity.

    Science.gov (United States)

    Wei, Hui; Bu, Yijie; Dai, Dawei

    2017-10-01

    To adapt to the environment and survive, most animals can control their behaviors by making decisions. The process of decision-making and responding according to cues in the environment is stable, sustainable, and learnable. Understanding how behaviors are regulated by neural circuits and the encoding and decoding mechanisms from stimuli to responses are important goals in neuroscience. From results observed in Drosophila experiments, the underlying decision-making process is discussed, and a neural circuit that implements a two-choice decision-making model is proposed to explain and reproduce the observations. Compared with previous two-choice decision making models, our model uses synaptic plasticity to explain changes in decision output given the same environment. Moreover, biological meanings of parameters of our decision-making model are discussed. In this paper, we explain at the micro-level (i.e., neurons and synapses) how observable decision-making behavior at the macro-level is acquired and achieved.

  8. Engagement of neural circuits underlying 2D spatial navigation in a rodent virtual reality system.

    Science.gov (United States)

    Aronov, Dmitriy; Tank, David W

    2014-10-22

    Virtual reality (VR) enables precise control of an animal's environment and otherwise impossible experimental manipulations. Neural activity in rodents has been studied on virtual 1D tracks. However, 2D navigation imposes additional requirements, such as the processing of head direction and environment boundaries, and it is unknown whether the neural circuits underlying 2D representations can be sufficiently engaged in VR. We implemented a VR setup for rats, including software and large-scale electrophysiology, that supports 2D navigation by allowing rotation and walking in any direction. The entorhinal-hippocampal circuit, including place, head direction, and grid cells, showed 2D activity patterns similar to those in the real world. Furthermore, border cells were observed, and hippocampal remapping was driven by environment shape, suggesting functional processing of virtual boundaries. These results illustrate that 2D spatial representations can be engaged by visual and rotational vestibular stimuli alone and suggest a novel VR tool for studying rat navigation.

  9. Homology and homoplasy of swimming behaviors and neural circuits in the Nudipleura (Mollusca, Gastropoda, Opisthobranchia)

    Science.gov (United States)

    Newcomb, James M.; Sakurai, Akira; Lillvis, Joshua L.; Gunaratne, Charuni A.; Katz, Paul S.

    2012-01-01

    How neural circuit evolution relates to behavioral evolution is not well understood. Here the relationship between neural circuits and behavior is explored with respect to the swimming behaviors of the Nudipleura (Mollusca, Gastropoda, Opithobranchia). Nudipleura is a diverse monophyletic clade of sea slugs among which only a small percentage of species can swim. Swimming falls into a limited number of categories, the most prevalent of which are rhythmic left–right body flexions (LR) and rhythmic dorsal–ventral body flexions (DV). The phylogenetic distribution of these behaviors suggests a high degree of homoplasy. The central pattern generator (CPG) underlying DV swimming has been well characterized in Tritonia diomedea and in Pleurobranchaea californica. The CPG for LR swimming has been elucidated in Melibe leonina and Dendronotus iris, which are more closely related. The CPGs for the categorically distinct DV and LR swimming behaviors consist of nonoverlapping sets of homologous identified neurons, whereas the categorically similar behaviors share some homologous identified neurons, although the exact composition of neurons and synapses in the neural circuits differ. The roles played by homologous identified neurons in categorically distinct behaviors differ. However, homologous identified neurons also play different roles even in the swim CPGs of the two LR swimming species. Individual neurons can be multifunctional within a species. Some of those functions are shared across species, whereas others are not. The pattern of use and reuse of homologous neurons in various forms of swimming and other behaviors further demonstrates that the composition of neural circuits influences the evolution of behaviors. PMID:22723353

  10. Neural circuits underlying mother's voice perception predict social communication abilities in children.

    Science.gov (United States)

    Abrams, Daniel A; Chen, Tianwen; Odriozola, Paola; Cheng, Katherine M; Baker, Amanda E; Padmanabhan, Aarthi; Ryali, Srikanth; Kochalka, John; Feinstein, Carl; Menon, Vinod

    2016-05-31

    The human voice is a critical social cue, and listeners are extremely sensitive to the voices in their environment. One of the most salient voices in a child's life is mother's voice: Infants discriminate their mother's voice from the first days of life, and this stimulus is associated with guiding emotional and social function during development. Little is known regarding the functional circuits that are selectively engaged in children by biologically salient voices such as mother's voice or whether this brain activity is related to children's social communication abilities. We used functional MRI to measure brain activity in 24 healthy children (mean age, 10.2 y) while they attended to brief (social function. Compared to female control voices, mother's voice elicited greater activity in primary auditory regions in the midbrain and cortex; voice-selective superior temporal sulcus (STS); the amygdala, which is crucial for processing of affect; nucleus accumbens and orbitofrontal cortex of the reward circuit; anterior insula and cingulate of the salience network; and a subregion of fusiform gyrus associated with face perception. The strength of brain connectivity between voice-selective STS and reward, affective, salience, memory, and face-processing regions during mother's voice perception predicted social communication skills. Our findings provide a novel neurobiological template for investigation of typical social development as well as clinical disorders, such as autism, in which perception of biologically and socially salient voices may be impaired.

  11. Age differences in the impact of peers on adolescents’ and adults’ neural response to reward

    Directory of Open Access Journals (Sweden)

    Ashley R. Smith

    2015-02-01

    Full Text Available Prior research suggests that increased adolescent risk-taking in the presence of peers may be linked to the influence of peers on the valuation and processing of rewards during decision-making. The current study explores this idea by examining how peer observation impacts the processing of rewards when such processing is isolated from other facets of risky decision-making (e.g. risk-perception and preference, inhibitory processing, etc.. In an fMRI paradigm, a sample of adolescents (ages 14–19 and adults (ages 25–35 completed a modified High/Low Card Guessing Task that included rewarded and un-rewarded trials. Social context was manipulated by having participants complete the task both alone and while being observed by two, same-age, same-sex peers. Results indicated an interaction of age and social context on the activation of reward circuitry during the receipt of reward; when observed by peers adolescents exhibited greater ventral striatal activation than adults, but no age-related differences were evinced when the task was completed alone. These findings suggest that, during adolescence, peers influence recruitment of reward-related regions even when they are engaged outside of the context of risk-taking. Implications for engagement in prosocial, as well as risky, behaviors during adolescence are discussed.

  12. Age Differences in the Impact of Peers on Adolescents’ and Adults’ Neural Response to Reward

    Science.gov (United States)

    Smith, Ashley R.; Steinberg, Laurence; Strang, Nicole; Chein, Jason

    2014-01-01

    Prior research suggests that increased adolescent risk-taking in the presence of peers may be linked to the influence of peers on the valuation and processing of rewards during decision-making. The current study explores this idea by examining how peer observation impacts the processing of rewards when such processing is isolated from other facets of risky decision-making (e.g. risk-perception and preference, inhibitory processing, etc.). In an fMRI paradigm, a sample of adolescents (ages 14–19) and adults (ages 25–35) completed a modified High/Low Card Guessing Task that included rewarded and un-rewarded trials. Social context was manipulated by having participants complete the task both alone and while being observed by two, same-age, same-sex peers. Results indicated an interaction of age and social context on the activation of reward circuitry during the receipt of reward; when observed by peers adolescents exhibited greater ventral striatal activation than adults, but no age-related differences were evinced when the task was completed alone. These findings suggest that, during adolescence, peers influence recruitment of reward-related regions even when they are engaged outside of the context of risk-taking. Implications for engagement in prosocial, as well as risky, behaviors during adolescence are discussed. PMID:25280778

  13. Age differences in the impact of peers on adolescents' and adults' neural response to reward.

    Science.gov (United States)

    Smith, Ashley R; Steinberg, Laurence; Strang, Nicole; Chein, Jason

    2015-02-01

    Prior research suggests that increased adolescent risk-taking in the presence of peers may be linked to the influence of peers on the valuation and processing of rewards during decision-making. The current study explores this idea by examining how peer observation impacts the processing of rewards when such processing is isolated from other facets of risky decision-making (e.g. risk-perception and preference, inhibitory processing, etc.). In an fMRI paradigm, a sample of adolescents (ages 14-19) and adults (ages 25-35) completed a modified High/Low Card Guessing Task that included rewarded and un-rewarded trials. Social context was manipulated by having participants complete the task both alone and while being observed by two, same-age, same-sex peers. Results indicated an interaction of age and social context on the activation of reward circuitry during the receipt of reward; when observed by peers adolescents exhibited greater ventral striatal activation than adults, but no age-related differences were evinced when the task was completed alone. These findings suggest that, during adolescence, peers influence recruitment of reward-related regions even when they are engaged outside of the context of risk-taking. Implications for engagement in prosocial, as well as risky, behaviors during adolescence are discussed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Effects of emotion and reward motivation on neural correlates of episodic memory encoding: a PET study.

    Science.gov (United States)

    Shigemune, Yayoi; Abe, Nobuhito; Suzuki, Maki; Ueno, Aya; Mori, Etsuro; Tashiro, Manabu; Itoh, Masatoshi; Fujii, Toshikatsu

    2010-05-01

    It is known that emotion and reward motivation promote long-term memory formation. It remains unclear, however, how and where emotion and reward are integrated during episodic memory encoding. In the present study, subjects were engaged in intentional encoding of photographs under four different conditions that were made by combining two factors (emotional valence, negative or neutral; and monetary reward value, high or low for subsequent successful recognition) during H2 15O positron emission tomography (PET) scanning. As for recognition performance, we found significant main effects of emotional valence (negative>neutral) and reward value (high value>low value), without an interaction between the two factors. Imaging data showed that the left amygdala was activated during the encoding conditions of negative pictures relative to neutral pictures, and the left orbitofrontal cortex was activated during the encoding conditions of high reward pictures relative to low reward pictures. In addition, conjunction analysis of these two main effects detected right hippocampal activation. Although we could not find correlations between recognition performance and activity of these three regions, we speculate that the right hippocampus may integrate the effects of emotion (processed in the amygdala) and monetary reward (processed in the orbitofrontal cortex) on episodic memory encoding. 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  15. Priming Neural Circuits to Modulate Spinal Reflex Excitability

    Science.gov (United States)

    Estes, Stephen P.; Iddings, Jennifer A.; Field-Fote, Edelle C.

    2017-01-01

    While priming is most often thought of as a strategy for modulating neural excitability to facilitate voluntary motor control, priming stimulation can also be utilized to target spinal reflex excitability. In this application, priming can be used to modulate the involuntary motor output that often follows central nervous system injury. Individuals with spinal cord injury (SCI) often experience spasticity, for which antispasmodic medications are the most common treatment. Physical therapeutic/electroceutic interventions offer an alternative treatment for spasticity, without the deleterious side effects that can accompany pharmacological interventions. While studies of physical therapeutic/electroceutic interventions have been published, a systematic comparison of these approaches has not been performed. The purpose of this study was to compare four non-pharmacological interventions to a sham-control intervention to assess their efficacy for spasticity reduction. Participants were individuals (n = 10) with chronic SCI (≥1 year) who exhibited stretch-induced quadriceps spasticity. Spasticity was quantified using the pendulum test before and at two time points after (immediate, 45 min delayed) each of four different physical therapeutic/electroceutic interventions, plus a sham-control intervention. Interventions included stretching, cyclic passive movement (CPM), transcutaneous spinal cord stimulation (tcSCS), and transcranial direct current stimulation (tDCS). The sham-control intervention consisted of a brief ramp-up and ramp-down of knee and ankle stimulation while reclined with legs extended. The order of interventions was randomized, and each was tested on a separate day with at least 48 h between sessions. Compared to the sham-control intervention, stretching, CPM, and tcSCS were associated with a significantly greater reduction in spasticity immediately after treatment. While the immediate effect was largest for stretching, the reduction persisted

  16. Biologically based neural circuit modelling for the study of fear learning and extinction

    Science.gov (United States)

    Nair, Satish S.; Paré, Denis; Vicentic, Aleksandra

    2016-11-01

    The neuronal systems that promote protective defensive behaviours have been studied extensively using Pavlovian conditioning. In this paradigm, an initially neutral-conditioned stimulus is paired with an aversive unconditioned stimulus leading the subjects to display behavioural signs of fear. Decades of research into the neural bases of this simple behavioural paradigm uncovered that the amygdala, a complex structure comprised of several interconnected nuclei, is an essential part of the neural circuits required for the acquisition, consolidation and expression of fear memory. However, emerging evidence from the confluence of electrophysiological, tract tracing, imaging, molecular, optogenetic and chemogenetic methodologies, reveals that fear learning is mediated by multiple connections between several amygdala nuclei and their distributed targets, dynamical changes in plasticity in local circuit elements as well as neuromodulatory mechanisms that promote synaptic plasticity. To uncover these complex relations and analyse multi-modal data sets acquired from these studies, we argue that biologically realistic computational modelling, in conjunction with experiments, offers an opportunity to advance our understanding of the neural circuit mechanisms of fear learning and to address how their dysfunction may lead to maladaptive fear responses in mental disorders.

  17. Large scale neural circuit mapping data analysis accelerated with the graphical processing unit (GPU)

    Science.gov (United States)

    Shi, Yulin; Veidenbaum, Alexander V.; Nicolau, Alex; Xu, Xiangmin

    2014-01-01

    Background Modern neuroscience research demands computing power. Neural circuit mapping studies such as those using laser scanning photostimulation (LSPS) produce large amounts of data and require intensive computation for post-hoc processing and analysis. New Method Here we report on the design and implementation of a cost-effective desktop computer system for accelerated experimental data processing with recent GPU computing technology. A new version of Matlab software with GPU enabled functions is used to develop programs that run on Nvidia GPUs to harness their parallel computing power. Results We evaluated both the central processing unit (CPU) and GPU-enabled computational performance of our system in benchmark testing and practical applications. The experimental results show that the GPU-CPU co-processing of simulated data and actual LSPS experimental data clearly outperformed the multi-core CPU with up to a 22x speedup, depending on computational tasks. Further, we present a comparison of numerical accuracy between GPU and CPU computation to verify the precision of GPU computation. In addition, we show how GPUs can be effectively adapted to improve the performance of commercial image processing software such as Adobe Photoshop. Comparison with Existing Method(s) To our best knowledge, this is the first demonstration of GPU application in neural circuit mapping and electrophysiology-based data processing. Conclusions Together, GPU enabled computation enhances our ability to process large-scale data sets derived from neural circuit mapping studies, allowing for increased processing speeds while retaining data precision. PMID:25277633

  18. Large-scale neural circuit mapping data analysis accelerated with the graphical processing unit (GPU).

    Science.gov (United States)

    Shi, Yulin; Veidenbaum, Alexander V; Nicolau, Alex; Xu, Xiangmin

    2015-01-15

    Modern neuroscience research demands computing power. Neural circuit mapping studies such as those using laser scanning photostimulation (LSPS) produce large amounts of data and require intensive computation for post hoc processing and analysis. Here we report on the design and implementation of a cost-effective desktop computer system for accelerated experimental data processing with recent GPU computing technology. A new version of Matlab software with GPU enabled functions is used to develop programs that run on Nvidia GPUs to harness their parallel computing power. We evaluated both the central processing unit (CPU) and GPU-enabled computational performance of our system in benchmark testing and practical applications. The experimental results show that the GPU-CPU co-processing of simulated data and actual LSPS experimental data clearly outperformed the multi-core CPU with up to a 22× speedup, depending on computational tasks. Further, we present a comparison of numerical accuracy between GPU and CPU computation to verify the precision of GPU computation. In addition, we show how GPUs can be effectively adapted to improve the performance of commercial image processing software such as Adobe Photoshop. To our best knowledge, this is the first demonstration of GPU application in neural circuit mapping and electrophysiology-based data processing. Together, GPU enabled computation enhances our ability to process large-scale data sets derived from neural circuit mapping studies, allowing for increased processing speeds while retaining data precision. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Neural learning circuits utilizing nano-crystalline silicon transistors and memristors.

    Science.gov (United States)

    Cantley, Kurtis D; Subramaniam, Anand; Stiegler, Harvey J; Chapman, Richard A; Vogel, Eric M

    2012-04-01

    Properties of neural circuits are demonstrated via SPICE simulations and their applications are discussed. The neuron and synapse subcircuits include ambipolar nano-crystalline silicon transistor and memristor device models based on measured data. Neuron circuit characteristics and the Hebbian synaptic learning rule are shown to be similar to biology. Changes in the average firing rate learning rule depending on various circuit parameters are also presented. The subcircuits are then connected into larger neural networks that demonstrate fundamental properties including associative learning and pulse coincidence detection. Learned extraction of a fundamental frequency component from noisy inputs is demonstrated. It is then shown that if the fundamental sinusoid of one neuron input is out of phase with the rest, its synaptic connection changes differently than the others. Such behavior indicates that the system can learn to detect which signals are important in the general population, and that there is a spike-timing-dependent component of the learning mechanism. Finally, future circuit design and considerations are discussed, including requirements for the memristive device.

  20. Activation of mesocorticolimbic reward circuits for assessment of relief of ongoing pain: a potential biomarker of efficacy.

    Science.gov (United States)

    Xie, Jennifer Y; Qu, Chaoling; Patwardhan, Amol; Ossipov, Michael H; Navratilova, Edita; Becerra, Lino; Borsook, David; Porreca, Frank

    2014-08-01

    Preclinical assessment of pain has increasingly explored operant methods that may allow behavioral assessment of ongoing pain. In animals with incisional injury, peripheral nerve block produces conditioned place preference (CPP) and activates the mesolimbic dopaminergic reward pathway. We hypothesized that activation of this circuit could serve as a neurochemical output measure of relief of ongoing pain. Medications commonly used clinically, including gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs), were evaluated in models of post-surgical (1 day after incision) or neuropathic (14 days after spinal nerve ligation [SNL]) pain to determine whether the clinical efficacy profile of these drugs in these pain conditions was reflected by extracellular dopamine (DA) release in the nucleus accumbens (NAc) shell. Microdialysis was performed in awake rats. Basal DA levels were not significantly different between experimental groups, and no significant treatment effects were seen in sham-operated animals. Consistent with clinical observation, spinal clonidine produced CPP and produced a dose-related increase in net NAc DA release in SNL rats. Gabapentin, commonly used to treat neuropathic pain, produced increased NAc DA in rats with SNL but not in animals with incisional, injury. In contrast, ketorolac or naproxen produced increased NAc DA in animals with incisional but not neuropathic pain. Increased extracellular NAc DA release was consistent with CPP and was observed selectively with treatments commonly used clinically for post-surgical or neuropathic pain. Evaluation of NAc DA efflux in animal pain models may represent an objective neurochemical assay that may serve as a biomarker of efficacy for novel pain-relieving mechanisms. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Activation of mesocorticolimbic reward circuits for assessment of relief of ongoing pain: a potential biomarker of efficacy

    Science.gov (United States)

    Xie, Jennifer Y.; Qu, Chaoling; Patwardhan, Amol; Ossipov, Michael H.; Navratilova, Edita; Becerra, Lino; Borsook, David; Porreca, Frank

    2014-01-01

    Preclinical assessment of pain has increasingly explored operant methods that may allow behavioral assessment of ongoing pain. In animals with incisional injury, peripheral nerve block produces conditioned place preference (CPP) and activates the mesolimbic dopaminergic reward pathway. We hypothesized that activation of this circuit could serve as a neurochemical output measure of relief of ongoing pain. Medications commonly used clinically including gabapentin and non-steroidal anti-inflammatory drugs (NSAIDs) were evaluated in models of post-surgical (one day following incision) or neuropathic (14 days following spinal nerve ligation, SNL) pain to determine if the clinical efficacy profile of these drugs in these pain conditions was reflected by extracellular dopamine (DA) release in the nucleus accumbens (NAc) shell. Microdialysis was performed in awake rats. Basal DA levels were not significantly different between experimental groups and no significant treatment effects were seen in sham-operated animals. Consistent with clinical observation, spinal clonidine produced CPP and produced a dose-related increase in net NAc DA release in SNL rats. Gabapentin, commonly used to treat neuropathic pain produced increased NAc DA in rats with SNL, but not in animals with incisional, injury. In contrast, ketorolac or naproxen produced increased NAc DA in animals with incisional, but not neuropathic, pain. Increased extracellular NAc DA release was consistent with CPP and observed selectively with treatments commonly used clinically for post-surgical or neuropathic pain. Evaluation of NAc DA efflux in animal pain models may represent an objective neurochemical assay that may serve as a biomarker of efficacy for novel pain-relieving mechanisms. PMID:24861580

  2. Circuit models and experimental noise measurements of micropipette amplifiers for extracellular neural recordings from live animals.

    Science.gov (United States)

    Chen, Chang Hao; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Klug, Achim; Lei, Tim C

    2014-01-01

    Glass micropipettes are widely used to record neural activity from single neurons or clusters of neurons extracellularly in live animals. However, to date, there has been no comprehensive study of noise in extracellular recordings with glass micropipettes. The purpose of this work was to assess various noise sources that affect extracellular recordings and to create model systems in which novel micropipette neural amplifier designs can be tested. An equivalent circuit of the glass micropipette and the noise model of this circuit, which accurately describe the various noise sources involved in extracellular recordings, have been developed. Measurement schemes using dead brain tissue as well as extracellular recordings from neurons in the inferior colliculus, an auditory brain nucleus of an anesthetized gerbil, were used to characterize noise performance and amplification efficacy of the proposed micropipette neural amplifier. According to our model, the major noise sources which influence the signal to noise ratio are the intrinsic noise of the neural amplifier and the thermal noise from distributed pipette resistance. These two types of noise were calculated and measured and were shown to be the dominating sources of background noise for in vivo experiments.

  3. Circuit Models and Experimental Noise Measurements of Micropipette Amplifiers for Extracellular Neural Recordings from Live Animals

    Directory of Open Access Journals (Sweden)

    Chang Hao Chen

    2014-01-01

    Full Text Available Glass micropipettes are widely used to record neural activity from single neurons or clusters of neurons extracellularly in live animals. However, to date, there has been no comprehensive study of noise in extracellular recordings with glass micropipettes. The purpose of this work was to assess various noise sources that affect extracellular recordings and to create model systems in which novel micropipette neural amplifier designs can be tested. An equivalent circuit of the glass micropipette and the noise model of this circuit, which accurately describe the various noise sources involved in extracellular recordings, have been developed. Measurement schemes using dead brain tissue as well as extracellular recordings from neurons in the inferior colliculus, an auditory brain nucleus of an anesthetized gerbil, were used to characterize noise performance and amplification efficacy of the proposed micropipette neural amplifier. According to our model, the major noise sources which influence the signal to noise ratio are the intrinsic noise of the neural amplifier and the thermal noise from distributed pipette resistance. These two types of noise were calculated and measured and were shown to be the dominating sources of background noise for in vivo experiments.

  4. Neural Coding of Reward-Prediction Error Signals During Classical Conditioning With Attractive Faces

    National Research Council Canada - National Science Library

    Signe Bray; John O'Doherty

    2007-01-01

    .... Given that these stimuli appear to act as rewards, we set out to explore whether it was possible to establish conditioning in human subjects by pairing presentation of arbitrary affectively neutral...

  5. Changes in the spinal neural circuits are dependent on the movement speed of the visuomotor task

    Directory of Open Access Journals (Sweden)

    Shinji eKubota

    2015-12-01

    Full Text Available Previous studies have shown that spinal neural circuits are modulated by motor skill training. However, the effects of task movement speed on changes in spinal neural circuits have not been clarified. The aim of this research was to investigate whether spinal neural circuits were affected by task movement speed. Thirty-eight healthy subjects participated in this study. In experiment 1, the effects of task movement speed on the spinal neural circuits were examined. 18 subjects performed a visuomotor task involving ankle muscle slow (9 subjects or fast (9 subjects movement speed. Another 9 subjects performed a non-visuomotor task (controls in fast movement speed. The motor task training lasted for 20 min. The amounts of D1 inhibition and reciprocal Ia inhibition were measured using H-relfex condition-test paradigm and recorded before, and at 5, 15, and 30 min after the training session. In experiment 2, using transcranial magnetic stimulation (TMS, the effects of corticospinal descending inputs on the presynaptic inhibitory pathway were examined before and after performing either a visuomotor (8 subjects or a control task (8 subjects. All measurements were taken under resting conditions. The amount of D1 inhibition increased after the visuomotor task irrespective of movement speed (P < 0.01. The amount of reciprocal Ia inhibition increased with fast movement speed conditioning (P < 0.01, but was unchanged by slow movement speed conditioning. These changes lasted up to 15 min in D1 inhibition and 5 min in reciprocal Ia inhibition after the training session. The control task did not induce changes in D1 inhibition and reciprocal Ia inhibition. The TMS conditioned inhibitory effects of presynaptic inhibitory pathways decreased following visuomotor tasks (P < 0.01. The size of test H-reflex was almost the same size throughout experiments. The results suggest that supraspinal descending inputs for controlling joint movement are responsible for changes

  6. Coexistence of reward and unsupervised learning during the operant conditioning of neural firing rates.

    Directory of Open Access Journals (Sweden)

    Robert R Kerr

    Full Text Available A fundamental goal of neuroscience is to understand how cognitive processes, such as operant conditioning, are performed by the brain. Typical and well studied examples of operant conditioning, in which the firing rates of individual cortical neurons in monkeys are increased using rewards, provide an opportunity for insight into this. Studies of reward-modulated spike-timing-dependent plasticity (RSTDP, and of other models such as R-max, have reproduced this learning behavior, but they have assumed that no unsupervised learning is present (i.e., no learning occurs without, or independent of, rewards. We show that these models cannot elicit firing rate reinforcement while exhibiting both reward learning and ongoing, stable unsupervised learning. To fix this issue, we propose a new RSTDP model of synaptic plasticity based upon the observed effects that dopamine has on long-term potentiation and depression (LTP and LTD. We show, both analytically and through simulations, that our new model can exhibit unsupervised learning and lead to firing rate reinforcement. This requires that the strengthening of LTP by the reward signal is greater than the strengthening of LTD and that the reinforced neuron exhibits irregular firing. We show the robustness of our findings to spike-timing correlations, to the synaptic weight dependence that is assumed, and to changes in the mean reward. We also consider our model in the differential reinforcement of two nearby neurons. Our model aligns more strongly with experimental studies than previous models and makes testable predictions for future experiments.

  7. A neuroplasticity-inspired neural circuit for acoustic navigation with obstacle avoidance that learns smooth motion paths

    DEFF Research Database (Denmark)

    Shaikh, Danish; Manoonpong, Poramate

    2018-01-01

    avoiding obstacles. We have reported earlier on a neural circuit for acoustic navigation, inspired by neuroplasticity mechanisms, which learned stable robot motion paths for a simulated mobile robot. The circuit realised a reactive behaviour-based navigation architecture where a phonotaxis behaviour...

  8. Pain and suicidality: insights from reward and addiction neuroscience.

    Science.gov (United States)

    Elman, Igor; Borsook, David; Volkow, Nora D

    2013-10-01

    Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system's role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain- and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other "reward deficiency syndromes" and a new proposal for "enhanced anti-reward syndromes". We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. Published by Elsevier Ltd.

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

    Science.gov (United States)

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

    2013-04-01

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

  10. Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats.

    Science.gov (United States)

    Li, Xiao-Li; Yuan, Yong-Gui; Xu, Hua; Wu, Di; Gong, Wei-Gang; Geng, Lei-Yu; Wu, Fang-Fang; Tang, Hao; Xu, Lin; Zhang, Zhi-Jun

    2015-04-21

    Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment. Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray's Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats' depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests. The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats. These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats' depressive behaviors, suggesting a therapeutic target for further exploration. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  11. Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats

    Science.gov (United States)

    Li, Xiao-Li; Yuan, Yong-Gui; Xu, Hua; Wu, Di; Gong, Wei-Gang; Geng, Lei-Yu; Wu, Fang-Fang; Tang, Hao; Xu, Lin

    2015-01-01

    Background: Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment. Methods: Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray’s Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats’ depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests. Results: The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats. Conclusion: These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats’ depressive behaviors, suggesting a therapeutic target for further exploration. PMID:25899067

  12. Altered social reward and attention in anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Karli K Watson

    2010-09-01

    Full Text Available Dysfunctional social reward and social orienting attend a variety of neuropsychiatric disorders including autism, schizophrenia, social anxiety, and psychopathy. Here we show that similar social reward and attention dysfunction attend anorexia nervosa, a disorder defined by avoidance of food and extreme weight loss. We measured the implicit reward value of social stimuli for female participants with (n=11 and without (n=11 anorexia nervosa using an econometric choice task and also tracked gaze patterns during free viewing of images of female faces and bodies. As predicted, the reward value of viewing bodies varied inversely with observed body weight for women with anorexia but not neurotypical women, in contrast with their explicit ratings of attractiveness. Surprisingly, women with anorexia nervosa, unlike neurotypical women, did not find female faces rewarding and avoided looking at both the face and eyes—independent of observed body weight. These findings demonstrate comorbid dysfunction in the neural circuits mediating gustatory and social reward in anorexia nervosa.

  13. Implementing a Bayes Filter in a Neural Circuit: The Case of Unknown Stimulus Dynamics.

    Science.gov (United States)

    Sokoloski, Sacha

    2017-09-01

    In order to interact intelligently with objects in the world, animals must first transform neural population responses into estimates of the dynamic, unknown stimuli that caused them. The Bayesian solution to this problem is known as a Bayes filter, which applies Bayes' rule to combine population responses with the predictions of an internal model. The internal model of the Bayes filter is based on the true stimulus dynamics, and in this note, we present a method for training a theoretical neural circuit to approximately implement a Bayes filter when the stimulus dynamics are unknown. To do this we use the inferential properties of linear probabilistic population codes to compute Bayes' rule and train a neural network to compute approximate predictions by the method of maximum likelihood. In particular, we perform stochastic gradient descent on the negative log-likelihood of the neural network parameters with a novel approximation of the gradient. We demonstrate our methods on a finite-state, a linear, and a nonlinear filtering problem and show how the hidden layer of the neural network develops tuning curves consistent with findings in experimental neuroscience.

  14. Genetic manipulation of specific neural circuits by use of a viral vector system.

    Science.gov (United States)

    Kobayashi, Kenta; Kato, Shigeki; Kobayashi, Kazuto

    2017-01-05

    To understand the mechanisms underlying higher brain functions, we need to analyze the roles of specific neuronal pathways or cell types forming the complex neural networks. In the neuroscience field, the transgenic approach has provided a useful gene engineering tool for experimental studies of neural functions. The conventional transgenic technique requires the appropriate promoter regions that drive a neuronal type-specific gene expression, but the promoter sequences specifically functioning in each neuronal type are limited. Previously, we developed novel types of lentiviral vectors showing high efficiency of retrograde gene transfer in the central nervous system, termed highly efficient retrograde gene transfer (HiRet) vector and neuron-specific retrograde gene transfer (NeuRet) vector. The HiRet and NeuRet vectors enable genetical manipulation of specific neural pathways in diverse model animals in combination with conditional cell targeting, synaptic transmission silencing, and gene expression systems. These newly developed vectors provide powerful experimental strategies to investigate, more precisely, the machineries exerting various neural functions. In this review, we give an outline of the HiRet and NeuRet vectors and describe recent representative applications of these viral vectors for studies on neural circuits.

  15. Spiking neural circuits with dendritic stimulus processors : encoding, decoding, and identification in reproducing kernel Hilbert spaces.

    Science.gov (United States)

    Lazar, Aurel A; Slutskiy, Yevgeniy B

    2015-02-01

    We present a multi-input multi-output neural circuit architecture for nonlinear processing and encoding of stimuli in the spike domain. In this architecture a bank of dendritic stimulus processors implements nonlinear transformations of multiple temporal or spatio-temporal signals such as spike trains or auditory and visual stimuli in the analog domain. Dendritic stimulus processors may act on both individual stimuli and on groups of stimuli, thereby executing complex computations that arise as a result of interactions between concurrently received signals. The results of the analog-domain computations are then encoded into a multi-dimensional spike train by a population of spiking neurons modeled as nonlinear dynamical systems. We investigate general conditions under which such circuits faithfully represent stimuli and demonstrate algorithms for (i) stimulus recovery, or decoding, and (ii) identification of dendritic stimulus processors from the observed spikes. Taken together, our results demonstrate a fundamental duality between the identification of the dendritic stimulus processor of a single neuron and the decoding of stimuli encoded by a population of neurons with a bank of dendritic stimulus processors. This duality result enabled us to derive lower bounds on the number of experiments to be performed and the total number of spikes that need to be recorded for identifying a neural circuit.

  16. Neural circuit dynamics underlying accumulation of time-varying evidence during perceptual decision making

    Directory of Open Access Journals (Sweden)

    Kong-Fatt Wong

    2007-11-01

    Full Text Available How do neurons in a decision circuit integrate time-varying signals, in favor of or against alternative choice options? To address this question, we used a recurrent neural circuit model to simulate an experiment in which monkeys performed a direction-discrimination task on a visual motion stimulus. In a recent study, it was found that brief pulses of motion perturbed neural activity in the lateral intraparietal area (LIP, and exerted corresponding effects on the monkey's choices and response times. Our model reproduces the behavioral observations and replicates LIP activity which, depending on whether the direction of the pulse is the same or opposite to that of a preferred motion stimulus, increases or decreases persistently over a few hundred milliseconds. Furthermore, our model accounts for the observation that the pulse exerts a weaker influence on LIP neuronal responses when the pulse is late relative to motion stimulus onset. We show that this violation of time-shift invariance (TSI is consistent with a recurrent circuit mechanism of time integration. We further examine time integration using two consecutive pulses of the same or opposite motion directions. The induced changes in the performance are not additive, and the second of the paired pulses is less effective than its standalone impact, a prediction that is experimentally testable. Taken together, these findings lend further support for an attractor network model of time integration in perceptual decision making.

  17. Dynamical systems, attractors, and neural circuits [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Paul Miller

    2016-05-01

    Full Text Available Biology is the study of dynamical systems. Yet most of us working in biology have limited pedagogical training in the theory of dynamical systems, an unfortunate historical fact that can be remedied for future generations of life scientists. In my particular field of systems neuroscience, neural circuits are rife with nonlinearities at all levels of description, rendering simple methodologies and our own intuition unreliable. Therefore, our ideas are likely to be wrong unless informed by good models. These models should be based on the mathematical theories of dynamical systems since functioning neurons are dynamic—they change their membrane potential and firing rates with time. Thus, selecting the appropriate type of dynamical system upon which to base a model is an important first step in the modeling process. This step all too easily goes awry, in part because there are many frameworks to choose from, in part because the sparsely sampled data can be consistent with a variety of dynamical processes, and in part because each modeler has a preferred modeling approach that is difficult to move away from. This brief review summarizes some of the main dynamical paradigms that can arise in neural circuits, with comments on what they can achieve computationally and what signatures might reveal their presence within empirical data. I provide examples of different dynamical systems using simple circuits of two or three cells, emphasizing that any one connectivity pattern is compatible with multiple, diverse functions.

  18. A Circuit-Based Neural Network with Hybrid Learning of Backpropagation and Random Weight Change Algorithms

    Science.gov (United States)

    Yang, Changju; Kim, Hyongsuk; Adhikari, Shyam Prasad; Chua, Leon O.

    2016-01-01

    A hybrid learning method of a software-based backpropagation learning and a hardware-based RWC learning is proposed for the development of circuit-based neural networks. The backpropagation is known as one of the most efficient learning algorithms. A weak point is that its hardware implementation is extremely difficult. The RWC algorithm, which is very easy to implement with respect to its hardware circuits, takes too many iterations for learning. The proposed learning algorithm is a hybrid one of these two. The main learning is performed with a software version of the BP algorithm, firstly, and then, learned weights are transplanted on a hardware version of a neural circuit. At the time of the weight transplantation, a significant amount of output error would occur due to the characteristic difference between the software and the hardware. In the proposed method, such error is reduced via a complementary learning of the RWC algorithm, which is implemented in a simple hardware. The usefulness of the proposed hybrid learning system is verified via simulations upon several classical learning problems. PMID:28025566

  19. The role of motivation and reward neural systems in vocal communication in songbirds

    Science.gov (United States)

    Riters, Lauren V.

    2012-01-01

    Many vertebrates are highly motivated to communicate, suggesting that the consequences of communication may be rewarding. Past studies show that dopamine and opioids in the medial preoptic nucleus (mPOA) and ventral tegmental area (VTA) play distinct roles in motivation and reward. In songbirds, multiple lines of recent evidence indicate that the roles of dopamine and opioid activity in mPOA and VTA in male birdsong differ depending upon whether song is used to attract females (sexually-motivated) or is produced spontaneously (undirected). Evidence is reviewed supporting the hypotheses that 1) mPOA and VTA interact to influence the context in which a male sings, 2) distinct patterns of dopamine activity underlie the motivation to produce sexually-motivated and undirected song, 3) sexually-motivated communication is externally reinforced by opioids released as part of social interactions, and 4) undirected communication is facilitated and rewarded by immediate opioid release linked to the act of singing. PMID:22569510

  20. A spiking neural model for stable reinforcement of synapses based on multiple distal rewards.

    Science.gov (United States)

    O'Brien, Michael J; Srinivasa, Narayan

    2013-01-01

    In this letter, a novel critic-like algorithm was developed to extend the synaptic plasticity rule described in Florian (2007) and Izhikevich (2007) in order to solve the problem of learning multiple distal rewards simultaneously. The system is augmented with short-term plasticity (STP) to stabilize the learning dynamics, thereby increasing the system's learning capacity. A theoretical threshold is estimated for the number of distal rewards that this system can learn. The validity of the novel algorithm was verified by computer simulations.

  1. The integration of social influence and reward: Computational approaches and neural evidence.

    Science.gov (United States)

    Tomlin, Damon; Nedic, Andrea; Prentice, Deborah A; Holmes, Philip; Cohen, Jonathan D

    2017-05-24

    Decades of research have established that decision-making is dramatically impacted by both the rewards an individual receives and the behavior of others. How do these distinct influences exert their influence on an individual's actions, and can the resulting behavior be effectively captured in a computational model? To address this question, we employed a novel spatial foraging game in which groups of three participants sought to find the most rewarding location in an unfamiliar two-dimensional space. As the game transitioned from one block to the next, the availability of information regarding other group members was varied systematically, revealing the relative impacts of feedback from the environment and information from other group members on individual decision-making. Both reward-based and socially-based sources of information exerted a significant influence on behavior, and a computational model incorporating these effects was able to recapitulate several key trends in the behavioral data. In addition, our findings suggest how these sources were processed and combined during decision-making. Analysis of reaction time, location of gaze, and functional magnetic resonance imaging (fMRI) data indicated that these distinct sources of information were integrated simultaneously for each decision, rather than exerting their influence in a separate, all-or-none fashion across separate subsets of trials. These findings add to our understanding of how the separate influences of reward from the environment and information derived from other social agents are combined to produce decisions.

  2. Multivariate Neural Representations of Value during Reward Anticipation and Consummation in the Human Orbitofrontal Cortex

    Science.gov (United States)

    Yan, Chao; Su, Li; Wang, Yi; Xu, Ting; Yin, Da-zhi; Fan, Ming-xia; Deng, Ci-ping; Hu, Yang; Wang, Zhao-xin; Cheung, Eric F. C.; Lim, Kelvin O.; Chan, Raymond C. K.

    2016-01-01

    The role of the orbitofrontal cortex (OFC) in value processing is a focus of research. Conventional imaging analysis, where smoothing and averaging are employed, may not be sufficiently sensitive in studying the OFC, which has heterogeneous anatomical structures and functions. In this study, we employed representational similarity analysis (RSA) to reveal the multi-voxel fMRI patterns in the OFC associated with value processing during the anticipatory and the consummatory phases. We found that multi-voxel activation patterns in the OFC encoded magnitude and partial valence information (win vs. loss) but not outcome (favourable vs. unfavourable) during reward consummation. Furthermore, the lateral OFC rather than the medial OFC encoded loss information. Also, we found that OFC encoded values in a similar way to the ventral striatum (VS) or the anterior insula (AI) during reward anticipation regardless of motivated response and to the medial prefrontal cortex (MPFC) and the VS in reward consummation. In contrast, univariate analysis did not show changes of activation in the OFC. These findings suggest an important role of the OFC in value processing during reward anticipation and consummation. PMID:27378417

  3. Global Micro- and Macro-structural White Matter Alterations and the reward circuit in First-episode Antipsychotic-naïve Schizophrenia Patients. Preliminary Results

    DEFF Research Database (Denmark)

    Raghava, Jayachandra Mitta; Ebdrup, Bjørn Hylsebeck; Nielsen, Mette Ødegaard

    Achieva MR scanner. Whole brain DTI images were acquired using single shot spin-echo echo-planar imaging. Images were corrected for head movement, eddy current distortion and susceptibility artifacts. After the baseline data acquisition, the patients were treated for 6 weeks with amisulpride. 28 patients...... and 28 healthy controls were included in the follow-up analyses. We performed whole brain tractography using the FA skeleton as a seed and CSF mask as termination criteria. The reward circuit was tracked from left VTA to left nucleus accumbens, left anterior limb of internal capsule (ALIC) and left...

  4. Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity.

    Science.gov (United States)

    Corty, Megan M; Freeman, Marc R

    2013-11-11

    Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

  5. Distinct neural circuits underlie assessment of a diversity of natural dangers by American crows

    Science.gov (United States)

    Cross, Donna J.; Marzluff, John M.; Palmquist, Ila; Minoshima, Satoshi; Shimizu, Toru; Miyaoka, Robert

    2013-01-01

    Social animals encountering natural dangers face decisions such as whether to freeze, flee or harass the threat. The American crow, Corvus brachyrhynchos, conspicuously mobs dangers. We used positron emission tomography to test the hypothesis that distinct neuronal substrates underlie the crow's consistent behavioural response to different dangers. We found that crows activated brain regions associated with attention and arousal (nucleus isthmo-opticus/locus coeruleus), and with motor response (arcopallium), as they fixed their gaze on a threat. However, despite this consistent behavioural and neural response, the sight of a person who previously captured the crow, a person holding a dead crow and a taxidermy-mounted hawk activated distinct forebrain regions (amygdala, hippocampus and portion of the caudal nidopallium, respectively). We suggest that aspects of mobbing behaviour are guided by unique neural circuits that respond to differences in mental processing—learning, memory formation and multisensory discrimination—required to appropriately nuance a risky behaviour to specific dangers. PMID:23825209

  6. Distinct neural circuits underlie assessment of a diversity of natural dangers by American crows.

    Science.gov (United States)

    Cross, Donna J; Marzluff, John M; Palmquist, Ila; Minoshima, Satoshi; Shimizu, Toru; Miyaoka, Robert

    2013-08-22

    Social animals encountering natural dangers face decisions such as whether to freeze, flee or harass the threat. The American crow, Corvus brachyrhynchos, conspicuously mobs dangers. We used positron emission tomography to test the hypothesis that distinct neuronal substrates underlie the crow's consistent behavioural response to different dangers. We found that crows activated brain regions associated with attention and arousal (nucleus isthmo-opticus/locus coeruleus), and with motor response (arcopallium), as they fixed their gaze on a threat. However, despite this consistent behavioural and neural response, the sight of a person who previously captured the crow, a person holding a dead crow and a taxidermy-mounted hawk activated distinct forebrain regions (amygdala, hippocampus and portion of the caudal nidopallium, respectively). We suggest that aspects of mobbing behaviour are guided by unique neural circuits that respond to differences in mental processing-learning, memory formation and multisensory discrimination-required to appropriately nuance a risky behaviour to specific dangers.

  7. From circuits to behaviour in the amygdala

    Science.gov (United States)

    Janak, Patricia H.; Tye, Kay M.

    2015-01-01

    The amygdala has long been associated with emotion and motivation, playing an essential part in processing both fearful and rewarding environmental stimuli. How can a single structure be crucial for such different functions? With recent technological advances that allow for causal investigations of specific neural circuit elements, we can now begin to map the complex anatomical connections of the amygdala onto behavioural function. Understanding how the amygdala contributes to a wide array of behaviours requires the study of distinct amygdala circuits. PMID:25592533

  8. 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.

  9. States versus rewards: dissociable neural prediction error signals underlying model-based and model-free reinforcement learning.

    Science.gov (United States)

    Gläscher, Jan; Daw, Nathaniel; Dayan, Peter; O'Doherty, John P

    2010-05-27

    Reinforcement learning (RL) uses sequential experience with situations ("states") and outcomes to assess actions. Whereas model-free RL uses this experience directly, in the form of a reward prediction error (RPE), model-based RL uses it indirectly, building a model of the state transition and outcome structure of the environment, and evaluating actions by searching this model. A state prediction error (SPE) plays a central role, reporting discrepancies between the current model and the observed state transitions. Using functional magnetic resonance imaging in humans solving a probabilistic Markov decision task, we found the neural signature of an SPE in the intraparietal sulcus and lateral prefrontal cortex, in addition to the previously well-characterized RPE in the ventral striatum. This finding supports the existence of two unique forms of learning signal in humans, which may form the basis of distinct computational strategies for guiding behavior. Copyright 2010 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2013-04-01

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

  11. Neural Correlates of Rewarded Response Inhibition in Youth at Risk for Problematic Alcohol Use

    Directory of Open Access Journals (Sweden)

    Brenden Tervo-Clemmens

    2017-11-01

    Full Text Available Risk for substance use disorder (SUD is associated with poor response inhibition and heightened reward sensitivity. During adolescence, incentives improve performance on response inhibition tasks and increase recruitment of cortical control areas (Geier et al., 2010 associated with SUD (Chung et al., 2011. However, it is unknown whether incentives moderate the relationship between response inhibition and trait-level psychopathology and personality features of substance use risk. We examined these associations in the current project using a rewarded antisaccade (AS task (Geier et al., 2010 in youth at risk for substance use. Participants were 116 adolescents and young adults (ages 12–21 from the University of Pittsburgh site of the National Consortium on Adolescent Neurodevelopment and Alcohol [NCANDA] study, with neuroimaging data collected at baseline and 1 year follow up visits. Building upon previous work using this task in normative developmental samples (Geier et al., 2010 and adolescents with SUD (Chung et al., 2011, we examined both trial-wise BOLD responses and those associated with individual task-epochs (cue presentation, response preparation, and response and associated them with multiple substance use risk factors (externalizing and internalizing psychopathology, family history of substance use, and trait impulsivity. Results showed that externalizing psychopathology and high levels of trait impulsivity (positive urgency, SUPPS-P were associated with general decreases in antisaccade performance. Accompanying this main effect of poor performance, positive urgency was associated with reduced recruitment of the frontal eye fields (FEF and inferior frontal gyrus (IFG in both a priori regions of interest and at the voxelwise level. Consistent with previous work, monetary incentive improved antisaccade behavioral performance and was associated with increased activation in the striatum and cortical control areas. However, incentives did

  12. Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models

    Directory of Open Access Journals (Sweden)

    Caleb Andrew Doll

    2014-02-01

    Full Text Available Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent developmental processes are specifically impaired in autism spectrum disorders (ASDs. ASD genetic models in both mouse and Drosophila have pioneered our insights into normal activity-dependent neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic Fragile X syndrome (FXS, a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in activity-dependent critical period processes. The Fragile X Mental Retardation Protein (FMRP is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the activity-dependent remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor activity-dependent processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of activity-dependent mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model.

  13. Functional changes in the reward circuit in response to gaming-related cues after training with a commercial video game.

    Science.gov (United States)

    Gleich, Tobias; Lorenz, Robert C; Gallinat, Jürgen; Kühn, Simone

    2017-05-15

    In the present longitudinal study, we aimed to investigate video game training associated neuronal changes in reward processing using functional magnetic resonance imaging (fMRI). We recruited 48 healthy young participants which were assigned to one of 2 groups: A group in which participants were instructed to play a commercial video game ("Super Mario 64 DS") on a portable Nintendo DS handheld console at least 30minutes a day over a period of two months (video gaming group; VG) or to a matched passive control group (CG). Before and after the training phase, in both groups, fMRI imaging was conducted during passively viewing reward and punishment-related videos sequences recorded from the trained video game. The results show that video game training may lead to reward related decrease in neuronal activation in the dorsolateral prefrontal cortex (DLPFC) and increase in the hippocampus. Additionally, the decrease in DLPFC activation was associated with gaming related parameters experienced during playing. Specifically, we found that in the VG, gaming related parameters like performance, experienced fun and frustration (assessed during the training period) were correlated to decrease in reward related DLPFC activity. Thus, neuronal changes in terms of video game training seem to be highly related to the appetitive character and reinforcement schedule of the game. Those neuronal changes may also be related to the often reported video game associated improvements in cognitive functions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Combining Correlation-Based and Reward-Based Learning in Neural Control for Policy Improvement

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Kolodziejski, Christoph; Wörgötter, Florentin

    2013-01-01

    Classical conditioning (conventionally modeled as correlation-based learning) and operant conditioning (conventionally modeled as reinforcement learning or reward-based learning) have been found in biological systems. Evidence shows that these two mechanisms strongly involve learning about...... policy, i.e., it allows the controller to learn stabilizing the pole in the largest domain of initial conditions compared to the results obtained when using a single learning mechanism. This model can also find a successful control policy for goal-directed behavior, i.e., the robot can effectively learn...

  15. Association of Neural and Emotional Impacts of Reward Prediction Errors With Major Depression

    Science.gov (United States)

    Moutoussis, Michael; Smittenaar, Peter; Zeidman, Peter; Taylor, Tanja; Hrynkiewicz, Louise; Lam, Jordan; Skandali, Nikolina; Siegel, Jenifer Z.; Ousdal, Olga T.; Prabhu, Gita; Dayan, Peter; Fonagy, Peter; Dolan, Raymond J.

    2017-01-01

    Importance Major depressive disorder (MDD) is associated with deficits in representing reward prediction errors (RPEs), which are the difference between experienced and predicted reward. Reward prediction errors underlie learning of values in reinforcement learning models, are represented by phasic dopamine release, and are known to affect momentary mood. Objective To combine functional neuroimaging, computational modeling, and smartphone-based large-scale data collection to test, in the absence of learning-related concerns, the hypothesis that depression attenuates the impact of RPEs. Design, Setting, and Participants Functional magnetic resonance imaging (fMRI) data were collected on 32 individuals with moderate MDD and 20 control participants who performed a probabilistic reward task. A risky decision task with repeated happiness ratings as a measure of momentary mood was also tested in the laboratory in 74 participants and with a smartphone-based platform in 1833 participants. The study was conducted from November 20, 2012, to February 17, 2015. Main Outcomes and Measures Blood oxygen level–dependent activity was measured in ventral striatum, a dopamine target area known to represent RPEs. Momentary mood was measured during risky decision making. Results Of the 52 fMRI participants (mean [SD] age, 34.0 [9.1] years), 30 (58%) were women and 32 had MDD. Of the 74 participants in the laboratory risky decision task (mean age, 34.2 [10.3] years), 44 (59%) were women and 54 had MDD. Of the smartphone group, 543 (30%) had a depression history and 1290 (70%) had no depression history; 918 (50%) were women, and 593 (32%) were younger than 30 years. Contrary to previous results in reinforcement learning tasks, individuals with moderate depression showed intact RPE signals in ventral striatum (z = 3.16; P = .002) that did not differ significantly from controls (z = 0.91; P = .36). Symptom severity correlated with baseline mood parameters in laboratory (

  16. Reward cues in space: commonalities and differences in neural coding by hippocampal and ventral striatal ensembles.

    Science.gov (United States)

    Lansink, Carien S; Jackson, Jadin C; Lankelma, Jan V; Ito, Rutsuko; Robbins, Trevor W; Everitt, Barry J; Pennartz, Cyriel M A

    2012-09-05

    Forming place-reward associations critically depends on the integrity of the hippocampal-ventral striatal system. The ventral striatum (VS) receives a strong hippocampal input conveying spatial-contextual information, but it is unclear how this structure integrates this information to invigorate reward-directed behavior. Neuronal ensembles in rat hippocampus (HC) and VS were simultaneously recorded during a conditioning task in which navigation depended on path integration. In contrast to HC, ventral striatal neurons showed low spatial selectivity, but rather coded behavioral task phases toward reaching goal sites. Outcome-predicting cues induced a remapping of firing patterns in the HC, consistent with its role in episodic memory. VS remapped in conjunction with the HC, indicating that remapping can take place in multiple brain regions engaged in the same task. Subsets of ventral striatal neurons showed a "flip" from high activity when cue lights were illuminated to low activity in intertrial intervals, or vice versa. The cues induced an increase in spatial information transmission and sparsity in both structures. These effects were paralleled by an enhanced temporal specificity of ensemble coding and a more accurate reconstruction of the animal's position from population firing patterns. Altogether, the results reveal strong differences in spatial processing between hippocampal area CA1 and VS, but indicate similarities in how discrete cues impact on this processing.

  17. The neural circuits and sensory channels mediating harsh touch sensation in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Wei; Kang, Lijun; Piggott, Beverly J; Feng, Zhaoyang; Xu, X Z Shawn

    2011-01-01

    Most animals can distinguish two distinct types of touch stimuli: gentle (innocuous) and harsh (noxious/painful) touch, however, the underlying mechanisms are not well understood. Caenorhabditis elegans is a useful model for the study of gentle touch sensation. However, little is known about harsh touch sensation in this organism. Here we characterize harsh touch sensation in C. elegans. We show that C. elegans exhibits differential behavioural responses to harsh touch and gentle touch. Laser ablations identify distinct sets of sensory neurons and interneurons required for harsh touch sensation at different body segments. Optogenetic stimulation of the circuitry can drive behaviour. Patch-clamp recordings reveal that TRP family and amiloride-sensitive Na(+) channels mediate touch-evoked currents in different sensory neurons. Our work identifies the neural circuits and characterizes the sensory channels mediating harsh touch sensation in C. elegans, establishing it as a genetic model for studying this sensory modality.

  18. Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans.

    Science.gov (United States)

    Kim, Byunghyuk; Emmons, Scott W

    2017-09-13

    Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

  19. Application of viral vectors to the study of neural connectivities and neural circuits in the marmoset brain.

    Science.gov (United States)

    Watakabe, Akiya; Sadakane, Osamu; Hata, Katsusuke; Ohtsuka, Masanari; Takaji, Masafumi; Yamamori, Tetsuo

    2017-03-01

    It is important to study the neural connectivities and functions in primates. For this purpose, it is critical to be able to transfer genes to certain neurons in the primate brain so that we can image the neuronal signals and analyze the function of the transferred gene. Toward this end, our team has been developing gene transfer systems using viral vectors. In this review, we summarize our current achievements as follows. 1) We compared the features of gene transfer using five different AAV serotypes in combination with three different promoters, namely, CMV, mouse CaMKII (CaMKII), and human synapsin 1 (hSyn1), in the marmoset cortex with those in the mouse and macaque cortices. 2) We used target-specific double-infection techniques in combination with TET-ON and TET-OFF using lentiviral retrograde vectors for enhanced visualization of neural connections. 3) We used an AAV-mediated gene transfer method to study the transcriptional control for amplifying fluorescent signals using the TET/TRE system in the primate neocortex. We also established systems for shRNA mediated gene targeting in a neocortical region where a gene is significantly expressed and for expressing the gene using the CMV promoter for an unexpressed neocortical area in the primate cortex using AAV vectors to understand the regulation of downstream genes. Our findings have demonstrated the feasibility of using viral vector mediated gene transfer systems for the study of primate cortical circuits using the marmoset as an animal model. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 354-372, 2017. © 2016 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.

  20. An Integrated Circuit for Simultaneous Extracellular Electrophysiology Recording and Optogenetic Neural Manipulation.

    Science.gov (United States)

    Chen, Chang Hao; McCullagh, Elizabeth A; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Mak, Pui In; Klug, Achim; Lei, Tim C

    2017-03-01

    The ability to record and to control action potential firing in neuronal circuits is critical to understand how the brain functions. The objective of this study is to develop a monolithic integrated circuit (IC) to record action potentials and simultaneously control action potential firing using optogenetics. A low-noise and high input impedance (or low input capacitance) neural recording amplifier is combined with a high current laser/light-emitting diode (LED) driver in a single IC. The low input capacitance of the amplifier (9.7 pF) was achieved by adding a dedicated unity gain stage optimized for high impedance metal electrodes. The input referred noise of the amplifier is [Formula: see text], which is lower than the estimated thermal noise of the metal electrode. Thus, the action potentials originating from a single neuron can be recorded with a signal-to-noise ratio of at least 6.6. The LED/laser current driver delivers a maximum current of 330 mA, which is adequate for optogenetic control. The functionality of the IC was tested with an anesthetized Mongolian gerbil and auditory stimulated action potentials were recorded from the inferior colliculus. Spontaneous firings of fifth (trigeminal) nerve fibers were also inhibited using the optogenetic protein Halorhodopsin. Moreover, a noise model of the system was derived to guide the design. A single IC to measure and control action potentials using optogenetic proteins is realized so that more complicated behavioral neuroscience research and the translational neural disorder treatments become possible in the future.

  1. Emergence of task-dependent representations in working memory circuits

    Directory of Open Access Journals (Sweden)

    Cristina eSavin

    2014-05-01

    Full Text Available A wealth of experimental evidence suggests that working memory circuits preferentially represent information that is behaviorally relevant. Still, we are missing a mechanistic account of how these representations come about. Here we provide a simple explanation for a range of experimental findings, in light of prefrontal circuits adapting to task constraints by reward-dependent learning. In particular, we model a neural network shaped by reward-modulated spike-timing dependent plasticity (r-STDP and homeostatic plasticity (intrinsic excitability and synaptic scaling. We show that the experimentally-observed neural representations naturally emerge in an initially unstructured circuit as it learns to solve several working memory tasks. These results point to a critical, and previously unappreciated, role for reward-dependent learning in shaping prefrontal cortex activity.

  2. Equivalent Circuit Parameters Estimation for PEM Fuel Cell Using RBF Neural Network and Enhanced Particle Swarm Optimization

    Directory of Open Access Journals (Sweden)

    Wen-Yeau Chang

    2013-01-01

    Full Text Available This paper proposes an equivalent circuit parameters measurement and estimation method for proton exchange membrane fuel cell (PEMFC. The parameters measurement method is based on current loading technique; in current loading test a no load PEMFC is suddenly turned on to obtain the waveform of the transient terminal voltage. After the equivalent circuit parameters were measured, a hybrid method that combines a radial basis function (RBF neural network and enhanced particle swarm optimization (EPSO algorithm is further employed for the equivalent circuit parameters estimation. The RBF neural network is adopted such that the estimation problem can be effectively processed when the considered data have different features and ranges. In the hybrid method, EPSO algorithm is used to tune the connection weights, the centers, and the widths of RBF neural network. Together with the current loading technique, the proposed hybrid estimation method can effectively estimate the equivalent circuit parameters of PEMFC. To verify the proposed approach, experiments were conducted to demonstrate the equivalent circuit parameters estimation of PEMFC. A practical PEMFC stack was purposely created to produce the common current loading activities of PEMFC for the experiments. The practical results of the proposed method were studied in accordance with the conditions for different loading conditions.

  3. Estimating neural background input with controlled and fast perturbations: A bandwidth comparison between inhibitory opsins and neural circuits

    Directory of Open Access Journals (Sweden)

    David Eriksson

    2016-08-01

    Full Text Available To test the importance of a certain cell type or brain area it is common to make a lack of function experiment in which the neuronal population of interest is inhibited. Here we review physiological and methodological constraints for making controlled perturbations using the corticothalamic circuit as an example. The brain with its many types of cells and rich interconnectivity offers many paths through which a perturbation can spread within a short time. To understand the side effects of the perturbation one should record from those paths. We find that ephaptic effects, gap-junctions, and fast chemical synapses are so fast that they can react to the perturbation during the few milliseconds it takes for an opsin to change the membrane potential. The slow chemical synapses, astrocytes, extracellular ions and vascular signals, will continue to give their physiological input for around 20 milliseconds before they also react to the perturbation. Although we show that some pathways can react within milliseconds the strength/speed reported in this review should be seen as an upper bound since we have omitted how polysynaptic signals are attenuated. Thus the number of additional recordings that has to be made to control for the perturbation side effects is expected to be fewer than proposed here. To summarize, the reviewed literature not only suggests that it is possible to make controlled lack of function experiments, but, it also suggests that such a lack of function experiment can be used to measure the context of local neural computations.

  4. Analgesic Neural Circuits Are Activated by Electroacupuncture at Two Sets of Acupoints

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    Man-Li Hu

    2016-01-01

    Full Text Available To investigate analgesic neural circuits activated by electroacupuncture (EA at different sets of acupoints in the brain, goats were stimulated by EA at set of Baihui-Santai acupoints or set of Housanli acupoints for 30 min. The pain threshold was measured using the potassium iontophoresis method. The levels of c-Fos were determined with Streptavidin-Biotin Complex immunohistochemistry. The results showed pain threshold induced by EA at set of Baihui-Santai acupoints was 44.74%±4.56% higher than that by EA at set of Housanli acupoints (32.64%±5.04%. Compared with blank control, EA at two sets of acupoints increased c-Fos expression in the medial septal nucleus (MSN, the arcuate nucleus (ARC, the nucleus amygdala basalis (AB, the lateral habenula nucleus (HL, the ventrolateral periaqueductal grey (vlPAG, the locus coeruleus (LC, the nucleus raphe magnus (NRM, the pituitary gland, and spinal cord dorsal horn (SDH. Compared with EA at set of Housanli points, EA at set of Baihui-Santai points induced increased c-Fos expression in AB but decrease in MSN, the paraventricular nucleus of the hypothalamus, HL, and SDH. It suggests that ARC-PAG-NRM/LC-SDH and the hypothalamus-pituitary may be the common activated neural pathways taking part in EA-induced analgesia at the two sets of acupoints.

  5. Information processing in micro and meso-scale neural circuits during normal and disease states

    Science.gov (United States)

    Luongo, Francisco

    Neural computation can occur at multiple spatial and temporal timescales. The sum total of all of these processes is to guide optimal behaviors within the context of the constraints imposed by the physical world. How the circuits of the brain achieves this goal represents a central question in systems neuroscience. Here I explore the many ways in which the circuits of the brain can process information at both the micro and meso scale. Understanding the way information is represented and processed in the brain could shed light on the neuropathology underlying complex neuropsychiatric diseases such as autism and schizophrenia. Chapter 2 establishes an experimental paradigm for assaying patterns of microcircuit activity and examines the role of dopaminergic modulation on prefrontal microcircuits. We find that dopamine type 2 (D2) receptor activation results in an increase in spontaneous activity while dopamine type 1 (D1) activation does not. Chapter 3 of this dissertation presents a study that illustrates how cholingergic activation normally produces what has been suggested as a neural substrate of attention; pairwise decorrelation in microcircuit activity. This study also shows that in two etiologicall distinct mouse models of autism, FMR1 knockout mice and Valproic Acid exposed mice, this ability to decorrelate in the presence of cholinergic activation is lost. This represents a putative microcircuit level biomarker of autism. Chapter 4 examines the structure/function relationship within the prefrontal microcircuit. Spontaneous activity in prefrontal microcircuits is shown to be organized according to a small world architecture. Interestingly, this architecture is important for one concrete function of neuronal microcircuits; the ability to produce temporally stereotyped patterns of activation. In the final chapter, we identify subnetworks in chronic intracranial electrocorticographic (ECoG) recordings using pairwise electrode coherence and dimensionality reduction

  6. Disrupted insula-based neural circuit organization and conflict interference in trauma-exposed youth

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    Hilary A. Marusak

    2015-01-01

    Full Text Available Childhood trauma exposure is a potent risk factor for psychopathology. Emerging research suggests that aberrant saliency processing underlies the link between early trauma exposure and later cognitive and socioemotional deficits that are hallmark of several psychiatric disorders. Here, we examine brain and behavioral responses during a face categorization conflict task, and relate these to intrinsic connectivity of the salience network (SN. The results demonstrate a unique pattern of SN dysfunction in youth exposed to trauma (n = 14 relative to comparison youth (n = 19 matched on age, sex, IQ, and sociodemographic risk. We find that trauma-exposed youth are more susceptible to conflict interference and this correlates with higher fronto-insular responses during conflict. Resting-state functional connectivity data collected in the same participants reveal increased connectivity of the insula to SN seed regions that is associated with diminished reward sensitivity, a critical risk/resilience trait following stress. In addition to altered intrinsic connectivity of the SN, we observed altered connectivity between the SN and default mode network (DMN in trauma-exposed youth. These data uncover network-level disruptions in brain organization following one of the strongest predictors of illness, early life trauma, and demonstrate the relevance of observed neural effects for behavior and specific symptom dimensions. SN dysfunction may serve as a diathesis that contributes to illness and negative outcomes following childhood trauma.

  7. Antagonistic Serotonergic and Octopaminergic Neural Circuits Mediate Food-Dependent Locomotory Behavior in Caenorhabditis elegans.

    Science.gov (United States)

    Churgin, Matthew A; McCloskey, Richard J; Peters, Emily; Fang-Yen, Christopher

    2017-08-16

    Biogenic amines are conserved signaling molecules that link food cues to behavior and metabolism in a wide variety of organisms. In the nematode Caenorhabditis elegans, the biogenic amines serotonin (5-HT) and octopamine regulate a number of food-related behaviors. Using a novel method for long-term quantitative behavioral imaging, we show that 5-HT and octopamine jointly influence locomotor activity and quiescence in feeding and fasting hermaphrodites, and we define the neural circuits through which this modulation occurs. We show that 5-HT produced by the ADF neurons acts via the SER-5 receptor in muscles and neurons to suppress quiescent behavior and promote roaming in fasting worms, whereas 5-HT produced by the NSM neurons acts on the MOD-1 receptor in AIY neurons to promote low-amplitude locomotor behavior characteristic of well fed animals. Octopamine, produced by the RIC neurons, acts via SER-3 and SER-6 receptors in SIA neurons to promote roaming behaviors characteristic of fasting animals. We find that 5-HT signaling is required for animals to assume food-appropriate behavior, whereas octopamine signaling is required for animals to assume fasting-appropriate behavior. The requirement for both neurotransmitters in both the feeding and fasting states enables increased behavioral adaptability. Our results define the molecular and neural pathways through which parallel biogenic amine signaling tunes behavior appropriately to nutrient conditions.SIGNIFICANCE STATEMENT Animals adjust behavior in response to environmental changes, such as fluctuations in food abundance, to maximize survival and reproduction. Biogenic amines, such as like serotonin, are conserved neurotransmitters that regulate behavior and metabolism in relation to energy status. Disruptions of biogenic amine signaling contribute to human neurological diseases of mood, appetite, and movement. In this study, we investigated the roles of the biogenic amines serotonin and octopamine in regulating

  8. Research Review: altered reward function in adolescent depression: what, when and how?

    Science.gov (United States)

    Forbes, Erika E; Dahl, Ronald E

    2012-01-01

    Conceptual models and recent evidence indicate that neural response to reward is altered in depression. Taking a developmental approach to investigating reward function in adolescent depression can elucidate the etiology, pathophysiology and course of depression, a disorder that typically begins during adolescence and has high rates of recurrence. This conceptual review describes the what, when and how of altered reward function in adolescent depression. With the goal of generating new, testable hypotheses within a developmental affective neuroscience framework, we critically review findings and suggest future directions. Peer-reviewed empirical papers for inclusion in this critical review were obtained by searching PubMed, PsycInfo and ScienceDirect for the years 1990-2010. A pattern of low striatal response and high medial prefrontal response to reward is evident in adolescents and adults with depression. Given the salience of social stimuli for positive affect and depression, reward function might be especially disrupted in response to social rewards. Because of changes in the dopamine system and reward function with aging, altered reward function in depression might be more evident during adolescence than later in life; however, low reward function may also be a stable characteristic of people who experience depression. Mechanisms of altered reward function in depression could include disrupted balance of corticostriatal circuit function, with disruption occurring as aberrant adolescent brain development. Future studies should examine responses to social rewards; employ longitudinal and prospective designs; and investigate patterns of functional connectivity in reward circuits. Understanding altered reward function in depression has potential implications for treatment development. A more rigorous approach to investigating anhedonia, threat-reward interactions and comorbid anxiety will be valuable to future progress in describing the role of reward function in

  9. Measuring the Neural Basis of Reward Anticipation and Reward Receipt in Attention-Deficit/Hyperactivity Disorder: The Importance of Task Design

    NARCIS (Netherlands)

    Plichta, M.M.; Scheres, A.P.J.

    2015-01-01

    In the May 2015 issue of the Journal, von Rhein et al. investigated ventral-striatal (VS) response during monetary reward anticipation and receipt using an impressively large sample (N = 350) of adolescents and young adults with attention-deficit/hyperactivity disorder (ADHD), their unaffected

  10. 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

  11. 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

  12. Navigating Monogamy: Nonapeptide Sensitivity in a Memory Neural Circuit May Shape Social Behavior and Mating Decisions

    Directory of Open Access Journals (Sweden)

    Alexander G. Ophir

    2017-07-01

    Full Text Available The role of memory in mating systems is often neglected despite the fact that most mating systems are defined in part by how animals use space. Monogamy, for example, is usually characterized by affiliative (e.g., pairbonding and defensive (e.g., mate guarding behaviors, but a high degree of spatial overlap in home range use is the easiest defining feature of monogamous animals in the wild. The nonapeptides vasopressin and oxytocin have been the focus of much attention for their importance in modulating social behavior, however this work has largely overshadowed their roles in learning and memory. To date, the understanding of memory systems and mechanisms governing social behavior have progressed relatively independently. Bridging these two areas will provide a deeper appreciation for understanding behavior, and in particular the mechanisms that mediate reproductive decision-making. Here, I argue that the ability to mate effectively as monogamous individuals is linked to the ability to track conspecifics in space. I discuss the connectivity across some well-known social and spatial memory nuclei, and propose that the nonapeptide receptors within these structures form a putative “socio-spatial memory neural circuit.” This purported circuit may function to integrate social and spatial information to shape mating decisions in a context-dependent fashion. The lateral septum and/or the nucleus accumbens, and neuromodulation therein, may act as an intermediary to relate socio-spatial information with social behavior. Identifying mechanisms responsible for relating information about the social world with mechanisms mediating mating tactics is crucial to fully appreciate the suite of factors driving reproductive decisions and social decision-making.

  13. The neural circuits recruited for the production of signs and fingerspelled words.

    Science.gov (United States)

    Emmorey, Karen; Mehta, Sonya; McCullough, Stephen; Grabowski, Thomas J

    2016-09-01

    Signing differs from typical non-linguistic hand actions because movements are not visually guided, finger movements are complex (particularly for fingerspelling), and signs are not produced as holistic gestures. We used positron emission tomography to investigate the neural circuits involved in the production of American Sign Language (ASL). Different types of signs (one-handed (articulated in neutral space), two-handed (neutral space), and one-handed body-anchored signs) were elicited by asking deaf native signers to produce sign translations of English words. Participants also fingerspelled (one-handed) printed English words. For the baseline task, participants indicated whether a word contained a descending letter. Fingerspelling engaged ipsilateral motor cortex and cerebellar cortex in contrast to both one-handed signs and the descender baseline task, which may reflect greater timing demands and complexity of handshape sequences required for fingerspelling. Greater activation in the visual word form area was also observed for fingerspelled words compared to one-handed signs. Body-anchored signs engaged bilateral superior parietal cortex to a greater extent than the descender baseline task and neutral space signs, reflecting the motor control and proprioceptive monitoring required to direct the hand toward a specific location on the body. Less activation in parts of the motor circuit was observed for two-handed signs compared to one-handed signs, possibly because, for half of the signs, handshape and movement goals were spread across the two limbs. Finally, the conjunction analysis comparing each sign type with the descender baseline task revealed common activation in the supramarginal gyrus bilaterally, which we interpret as reflecting phonological retrieval and encoding processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Navigating Monogamy: Nonapeptide Sensitivity in a Memory Neural Circuit May Shape Social Behavior and Mating Decisions.

    Science.gov (United States)

    Ophir, Alexander G

    2017-01-01

    The role of memory in mating systems is often neglected despite the fact that most mating systems are defined in part by how animals use space. Monogamy, for example, is usually characterized by affiliative (e.g., pairbonding) and defensive (e.g., mate guarding) behaviors, but a high degree of spatial overlap in home range use is the easiest defining feature of monogamous animals in the wild. The nonapeptides vasopressin and oxytocin have been the focus of much attention for their importance in modulating social behavior, however this work has largely overshadowed their roles in learning and memory. To date, the understanding of memory systems and mechanisms governing social behavior have progressed relatively independently. Bridging these two areas will provide a deeper appreciation for understanding behavior, and in particular the mechanisms that mediate reproductive decision-making. Here, I argue that the ability to mate effectively as monogamous individuals is linked to the ability to track conspecifics in space. I discuss the connectivity across some well-known social and spatial memory nuclei, and propose that the nonapeptide receptors within these structures form a putative "socio-spatial memory neural circuit." This purported circuit may function to integrate social and spatial information to shape mating decisions in a context-dependent fashion. The lateral septum and/or the nucleus accumbens, and neuromodulation therein, may act as an intermediary to relate socio-spatial information with social behavior. Identifying mechanisms responsible for relating information about the social world with mechanisms mediating mating tactics is crucial to fully appreciate the suite of factors driving reproductive decisions and social decision-making.

  15. Structural basis for cholinergic regulation of neural circuits in the mouse olfactory bulb.

    Science.gov (United States)

    Hamamoto, Masakazu; Kiyokage, Emi; Sohn, Jaerin; Hioki, Hiroyuki; Harada, Tamotsu; Toida, Kazunori

    2017-02-15

    Odor information is regulated by olfactory inputs, bulbar interneurons, and centrifugal inputs in the olfactory bulb (OB). Cholinergic neurons projecting from the nucleus of the horizontal limb of the diagonal band of Broca and the magnocellular preoptic nucleus are one of the primary centrifugal inputs to the OB. In this study, we focused on cholinergic regulation of the OB and analyzed neural morphology with a particular emphasis on the projection pathways of cholinergic neurons. Single-cell imaging of a specific neuron within dense fibers is critical to evaluate the structure and function of the neural circuits. We labeled cholinergic neurons by infection with virus vector and then reconstructed them three-dimensionally. We also examined the ultramicrostructure of synapses by electron microscopy tomography. To further clarify the function of cholinergic neurons, we performed confocal laser scanning microscopy to investigate whether other neurotransmitters are present within cholinergic axons in the OB. Our results showed the first visualization of complete cholinergic neurons, including axons projecting to the OB, and also revealed frequent axonal branching within the OB where it innervated multiple glomeruli in different areas. Furthermore, electron tomography demonstrated that cholinergic axons formed asymmetrical synapses with a morphological variety of thicknesses of the postsynaptic density. Although we have not yet detected the presence of other neurotransmitters, the range of synaptic morphology suggests multiple modes of transmission. The present study elucidates the ways that cholinergic neurons could contribute to the elaborate mechanisms involved in olfactory processing in the OB. J. Comp. Neurol. 525:574-591, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. The malleable brain: plasticity of neural circuits and behavior - a review from students to students.

    Science.gov (United States)

    Schaefer, Natascha; Rotermund, Carola; Blumrich, Eva-Maria; Lourenco, Mychael V; Joshi, Pooja; Hegemann, Regina U; Jamwal, Sumit; Ali, Nilufar; García Romero, Ezra Michelet; Sharma, Sorabh; Ghosh, Shampa; Sinha, Jitendra K; Loke, Hannah; Jain, Vishal; Lepeta, Katarzyna; Salamian, Ahmad; Sharma, Mahima; Golpich, Mojtaba; Nawrotek, Katarzyna; Paidi, Ramesh K; Shahidzadeh, Sheila M; Piermartiri, Tetsade; Amini, Elham; Pastor, Veronica; Wilson, Yvette; Adeniyi, Philip A; Datusalia, Ashok K; Vafadari, Benham; Saini, Vedangana; Suárez-Pozos, Edna; Kushwah, Neetu; Fontanet, Paula; Turner, Anthony J

    2017-06-20

    One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation and long-term depression, respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by long-term potentiation and long-term depression, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity. Read the Editorial Highlight for this article on doi: 10.1111/jnc.14102. © 2017 International Society for Neurochemistry.

  17. Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model

    Science.gov (United States)

    Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

    2016-01-01

    Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction. PMID:27617747

  18. Neural activity in the reward-related brain regions predicts implicit self-esteem: A novel validity test of psychological measures using neuroimaging.

    Science.gov (United States)

    Izuma, Keise; Kennedy, Kate; Fitzjohn, Alexander; Sedikides, Constantine; Shibata, Kazuhisa

    2018-03-01

    Self-esteem, arguably the most important attitudes an individual possesses, has been a premier research topic in psychology for more than a century. Following a surge of interest in implicit attitude measures in the 90s, researchers have tried to assess self-esteem implicitly to circumvent the influence of biases inherent in explicit measures. However, the validity of implicit self-esteem measures remains elusive. Critical tests are often inconclusive, as the validity of such measures is examined in the backdrop of imperfect behavioral measures. To overcome this serious limitation, we tested the neural validity of the most widely used implicit self-esteem measure, the implicit association test (IAT). Given the conceptualization of self-esteem as attitude toward the self, and neuroscience findings that the reward-related brain regions represent an individual's attitude or preference for an object when viewing its image, individual differences in implicit self-esteem should be associated with neural signals in the reward-related regions during passive-viewing of self-face (the most obvious representation of the self). Using multi-voxel pattern analysis (MVPA) on functional MRI (fMRI) data, we demonstrate that the neural signals in the reward-related regions were robustly associated with implicit (but not explicit) self-esteem, thus providing unique evidence for the neural validity of the self-esteem IAT. In addition, both implicit and explicit self-esteem were related, although differently, to neural signals in regions involved in self-processing. Our finding highlights the utility of neuroscience methods in addressing fundamental psychological questions and providing unique insights into important psychological constructs. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  19. Neural and personality correlates of individual differences related to the effects of acute tryptophan depletion on future reward evaluation.

    Science.gov (United States)

    Demoto, Yoshihiko; Okada, Go; Okamoto, Yasumasa; Kunisato, Yoshihiko; Aoyama, Shiori; Onoda, Keiichi; Munakata, Ayumi; Nomura, Michio; Tanaka, Saori C; Schweighofer, Nicolas; Doya, Kenji; Yamawaki, Shigeto

    2012-01-01

    In general, humans tend to discount the value of delayed reward. An increase in the rate of discounting leads to an inability to select a delayed reward over a smaller immediate reward (reward-delay impulsivity). Although deficits in the serotonergic system are implicated in this reward-delay impulsivity, there is individual variation in response to serotonin depletion. The aim of the present study was to investigate whether the effects of serotonin depletion on the ability to evaluate future reward are affected by individual personality traits or brain activation. Personality traits were assessed using the NEO-Five Factor Inventory and Temperament and Character Inventory. The central serotonergic levels of 16 healthy volunteers were manipulated by dietary tryptophan depletion. Subjects performed a delayed reward choice task that required the continuous estimation of reward value during functional magnetic resonance imaging scanning. Discounting rates were increased in 9 participants, but were unchanged or decreased in 7 participants in response to tryptophan depletion. Participants whose discounting rate was increased by tryptophan depletion had significantly higher neuroticism and lower self-directedness. Furthermore, tryptophan depletion differentially affected the groups in terms of hemodynamic responses to the value of predicted future reward in the right insula. These results suggest that individuals who have high neuroticism and low self-directedness as personality traits are particularly vulnerable to the effect of low serotonin on future reward evaluation accompanied by altered brain activation patterns. Copyright © 2012 S. Karger AG, Basel.

  20. The neural correlates of priming emotion and reward systems for conflict processing in alcoholics.

    Science.gov (United States)

    Schulte, T; Jung, Y-C; Sullivan, E V; Pfefferbaum, A; Serventi, M; Müller-Oehring, E M

    2016-11-04

    Emotional dysregulation in alcoholism (ALC) may result from disturbed inhibitory mechanisms. We therefore tested emotion and alcohol cue reactivity and inhibitory processes using negative priming. To test the neural correlates of cue reactivity and negative priming, 26 ALC and 26 age-matched controls underwent functional MRI performing a Stroop color match-to-sample task. In cue reactivity trials, task-irrelevant emotion and alcohol-related pictures were interspersed between color samples and color words. In negative priming trials, pictures primed the semantic content of an alcohol or emotion Stroop word. Behaviorally, both groups showed response facilitation to picture cue trials and response inhibition to primed trials. For cue reactivity to emotion and alcohol pictures, ALC showed midbrain-limbic activation. By contrast, controls activated frontoparietal executive control regions. Greater midbrain-hippocampal activation in ALC correlated with higher amounts of lifetime alcohol consumption and higher anxiety. With negative priming, ALC exhibited frontal cortical but not midbrain-hippocampal activation, similar to the pattern observed in controls. Higher frontal activation to alcohol-priming correlated with less craving and to emotion-priming with fewer depressive symptoms. The findings suggest that neurofunctional systems in ALC can be primed to deal with upcoming emotion- and alcohol-related conflict and can overcome the prepotent midbrain-limbic cue reactivity response.

  1. Acute genetic manipulation of neuronal activity for the functional dissection of neural circuits-a dream come true for the pioneers of behavioral genetics.

    Science.gov (United States)

    Yoshihara, Moto; Ito, Kei

    2012-03-01

    Abstract: This review summarizes technical development of the functional manipulation of specific neural circuits through genetic techniques in Drosophila. Long after pioneers' efforts for the genetic dissection of behavior using this organism as a model, analyses with acute activation of specific neural circuits have finally become feasible using transgenic Drosophila that expresses light-, heat-, or cold-activatable cation channels by xxx/upstream activation sequence (Gal4/UAS)-based induction system. This methodology opened a new avenue to dissect functions of neural circuits to make dreams of the pioneers into reality.

  2. Behavioral and Neural Manifestations of Reward Memory in Carriers of Low-Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor

    Directory of Open Access Journals (Sweden)

    Anni Richter

    2017-05-01

    Full Text Available Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2 availability in the striatum, and the DRD2 TaqIA (rs1800497 and C957T (rs6277 genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of

  3. Reward processing in neurodegenerative disease

    Science.gov (United States)

    Perry, David C.; Kramer, Joel H.

    2015-01-01

    Representation of reward value involves a distributed network including cortical and subcortical structures. Because neurodegenerative illnesses target specific anatomic networks that partially overlap with the reward circuit they would be predicted to have distinct impairments in reward processing. This review presents the existing evidence of reward processing changes in neurodegenerative diseases including mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease, as well as in healthy aging. Carefully distinguishing the different aspects of reward processing (primary rewards, secondary rewards, reward-based learning, and reward-based decision-making) and using tasks that differentiate the stages of processing reward will lead to improved understanding of this fundamental process and clarify a contributing cause of behavioral change in these illnesses. PMID:24417286

  4. Hybrid Spintronic-CMOS Spiking Neural Network with On-Chip Learning: Devices, Circuits, and Systems

    Science.gov (United States)

    Sengupta, Abhronil; Banerjee, Aparajita; Roy, Kaushik

    2016-12-01

    Over the past decade, spiking neural networks (SNNs) have emerged as one of the popular architectures to emulate the brain. In SNNs, information is temporally encoded and communication between neurons is accomplished by means of spikes. In such networks, spike-timing-dependent plasticity mechanisms require the online programing of synapses based on the temporal information of spikes transmitted by spiking neurons. In this work, we propose a spintronic synapse with decoupled spike-transmission and programing-current paths. The spintronic synapse consists of a ferromagnet-heavy-metal heterostructure where the programing current through the heavy metal generates spin-orbit torque to modulate the device conductance. Low programing energy and fast programing times demonstrate the efficacy of the proposed device as a nanoelectronic synapse. We perform a simulation study based on an experimentally benchmarked device-simulation framework to demonstrate the interfacing of such spintronic synapses with CMOS neurons and learning circuits operating in the transistor subthreshold region to form a network of spiking neurons that can be utilized for pattern-recognition problems.

  5. Impact of adolescent social experiences on behavior and neural circuits implicated in mental illnesses.

    Science.gov (United States)

    Burke, Andrew R; McCormick, Cheryl M; Pellis, Sergio M; Lukkes, Jodi L

    2017-05-01

    Negative social experiences during adolescence are central features for several stress-related mental illnesses. Social play fighting behavior in rats peaks during early adolescence and is essential for the final maturation of brain and behavior. Manipulation of the rat adolescent social experience alters many neurobehavioral measurements implicated in anxiety, depression, and substance abuse. In this review, we will highlight the importance of social play and the use of three separate social stress models (isolation-rearing, social defeat, and social instability stress) to disrupt the acquisition of this adaptive behavior. Social stress during adolescence leads to the development of anxiety and depressive behavior as well as escalated drug use in adulthood. Furthermore, sex- and age-dependent effects on the hormonal stress response following adolescent social stress are also observed. Finally, manipulation of the social experience during adolescence alters stress-related neural circuits and monoaminergic systems. Overall, positive social experiences among age-matched conspecifics during rat adolescence are critical for healthy neurobehavioral maturation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Segregated and overlapping neural circuits exist for the production of static and dynamic precision grip force

    Science.gov (United States)

    Neely, Kristina A.; Coombes, Stephen A.; Planetta, Peggy J.; Vaillancourt, David E.

    2011-01-01

    A central topic in sensorimotor neuroscience is the static-dynamic dichotomy that exists throughout the nervous system. Previous work examining motor unit synchronization reports that the activation strategy and timing of motor units differ for static and dynamic tasks. However, it remains unclear whether segregated or overlapping blood-oxygen-level-dependent (BOLD) activity exists in the brain for static and dynamic motor control. This study compared the neural circuits associated with the production of static force to those associated with the production of dynamic force pulses. To that end, healthy young adults (n = 17) completed static and dynamic precision grip force tasks during functional magnetic resonance imaging (fMRI). Both tasks activated core regions within the visuomotor network, including primary and sensory motor cortices, premotor cortices, multiple visual areas, putamen, and cerebellum. Static force was associated with unique activity in a right-lateralized cortical network including inferior parietal lobe, ventral premotor cortex, and dorsolateral prefrontal cortex. In contrast, dynamic force was associated with unique activity in left-lateralized and midline cortical regions, including supplementary motor area, superior parietal lobe, fusiform gyrus, and visual area V3. These findings provide the first neuroimaging evidence supporting a lateralized pattern of brain activity for the production of static and dynamic precision grip force. PMID:22109998

  7. The primary visual cortex in the neural circuit for visual orienting

    Science.gov (United States)

    Zhaoping, Li

    The primary visual cortex (V1) is traditionally viewed as remote from influencing brain's motor outputs. However, V1 provides the most abundant cortical inputs directly to the sensory layers of superior colliculus (SC), a midbrain structure to command visual orienting such as shifting gaze and turning heads. I will show physiological, anatomical, and behavioral data suggesting that V1 transforms visual input into a saliency map to guide a class of visual orienting that is reflexive or involuntary. In particular, V1 receives a retinotopic map of visual features, such as orientation, color, and motion direction of local visual inputs; local interactions between V1 neurons perform a local-to-global computation to arrive at a saliency map that highlights conspicuous visual locations by higher V1 responses. The conspicuous location are usually, but not always, where visual input statistics changes. The population V1 outputs to SC, which is also retinotopic, enables SC to locate, by lateral inhibition between SC neurons, the most salient location as the saccadic target. Experimental tests of this hypothesis will be shown. Variations of the neural circuit for visual orienting across animal species, with more or less V1 involvement, will be discussed. Supported by the Gatsby Charitable Foundation.

  8. The Neuropsychiatry of Hyperkinetic Movement Disorders: Insights from Neuroimaging into the Neural Circuit Bases of Dysfunction

    Directory of Open Access Journals (Sweden)

    Bradleigh D. Hayhow

    2013-09-01

    Full Text Available Background: Movement disorders, particularly those associated with basal ganglia disease, have a high rate of comorbid neuropsychiatric illness.Methods: We consider the pathophysiological basis of the comorbidity between movement disorders and neuropsychiatric illness by 1 reviewing the epidemiology of neuropsychiatric illness in a range of hyperkinetic movement disorders, and 2 correlating findings to evidence from studies that have utilized modern neuroimaging techniques to investigate these disorders. In addition to diseases classically associated with basal ganglia pathology, such as Huntington disease, Wilson disease, the neuroacanthocytoses, and diseases of brain iron accumulation, we include diseases associated with pathology of subcortical white matter tracts, brain stem nuclei, and the cerebellum, such as metachromatic leukodystrophy, dentatorubropallidoluysian atrophy, and the spinocerebellar ataxias.Conclusions: Neuropsychiatric symptoms are integral to a thorough phenomenological account of hyperkinetic movement disorders. Drawing on modern theories of cortico-subcortical circuits, we argue that these disorders can be conceptualized as disorders of complex subcortical networks with distinct functional architectures. Damage to any component of these complex information-processing networks can have variable and often profound consequences for the function of more remote neural structures, creating a diverse but nonetheless rational pattern of clinical symptomatology.

  9. Longitudinal changes in adolescent risk-taking: a comprehensive study of neural responses to rewards, pubertal development, and risk-taking behavior.

    Science.gov (United States)

    Braams, Barbara R; van Duijvenvoorde, Anna C K; Peper, Jiska S; Crone, Eveline A

    2015-05-06

    Prior studies have highlighted adolescence as a period of increased risk-taking, which is postulated to result from an overactive reward system in the brain. Longitudinal studies are pivotal for testing these brain-behavior relations because individual slopes are more sensitive for detecting change. The aim of the current study was twofold: (1) to test patterns of age-related change (i.e., linear, quadratic, and cubic) in activity in the nucleus accumbens, a key reward region in the brain, in relation to change in puberty (self-report and testosterone levels), laboratory risk-taking and self-reported risk-taking tendency; and (2) to test whether individual differences in pubertal development and risk-taking behavior were contributors to longitudinal change in nucleus accumbens activity. We included 299 human participants at the first time point and 254 participants at the second time point, ranging between ages 8-27 years, time points were separated by a 2 year interval. Neural responses to rewards, pubertal development (self-report and testosterone levels), laboratory risk-taking (balloon analog risk task; BART), and self-reported risk-taking tendency (Behavior Inhibition System/Behavior Activation System questionnaire) were collected at both time points. The longitudinal analyses confirmed the quadratic age pattern for nucleus accumbens activity to rewards (peaking in adolescence), and the same quadratic pattern was found for laboratory risk-taking (BART). Nucleus accumbens activity change was further related to change in testosterone and self-reported reward-sensitivity (BAS Drive). Thus, this longitudinal analysis provides new insight in risk-taking and reward sensitivity in adolescence: (1) confirming an adolescent peak in nucleus accumbens activity, and (2) underlining a critical role for pubertal hormones and individual differences in risk-taking tendency. Copyright © 2015 the authors 0270-6474/15/357226-13$15.00/0.

  10. Neural mechanisms underlying the reward-related enhancement of motivation when remembering episodic memories with high difficulty.

    Science.gov (United States)

    Shigemune, Yayoi; Tsukiura, Takashi; Nouchi, Rui; Kambara, Toshimune; Kawashima, Ryuta

    2017-04-04

    The motivation to receive rewards enhances episodic memories, and the motivation is modulated by task difficulty. In episodic retrieval, however, functional neuroimaging evidence regarding the motivation that mediates interactions between reward and task difficulty is scarce. The present fMRI study investigated this issue. During encoding performed without fMRI, participants encoded Japanese words using either deep or shallow strategies, which led to variation in difficulty level during subsequent retrieval. During retrieval with fMRI, participants recognized the target words in either high or low monetary reward conditions. In the behavioral results, a reward-related enhancement of memory was found only when the memory retrieval was difficult, and the rewarding effect on subjective motivation was greater in the retrieval of memories with high difficulty than those with low difficulty. The fMRI data showed that reward-related increases in the activation of the substantia nigra/ventral tegmental area (SN/VTA), medial temporal lobe (MTL), dorsomedial prefrontal cortex (dmPFC), and dorsolateral prefrontal cortex (dlPFC) were greater during the retrieval of memories with high difficulty than those with low difficulty. Furthermore, reward-related enhancement of functional connectivity between the SN/VTA and MTL and between the SN/VTA and dmPFC during the retrieval of memories with high difficulty was significantly correlated with reward-related increases of retrieval accuracy and subjective motivation. The reward-related enhancement of episodic retrieval and retrieval-related motivation could be most effective when the level of retrieval difficulty is optimized. Such reward-related enhancement of memory and motivation could be modulated by a network including the reward-related SN/VTA, motivation-related dmPFC, and memory-related MTL. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Natural and Drug Rewards Act on Common Neural Plasticity Mechanisms with ΔFosB as a Key Mediator

    Science.gov (United States)

    Pitchers, Kyle K.; Vialou, Vincent; Nestler, Eric J.; Laviolette, Steven R.; Lehman, Michael N.

    2013-01-01

    Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. Recent evidence suggests that natural rewards may cause similar changes in the NAc, suggesting that drugs may activate mechanisms of plasticity shared with natural rewards, and allowing for unique interplay between natural and drug rewards. In this study, we demonstrate that sexual experience in male rats when followed by short or prolonged periods of loss of sex reward causes enhanced amphetamine reward, indicated by sensitized conditioned place preference for low-dose (0.5 mg/kg) amphetamine. Moreover, the onset, but not the longer-term expression, of enhanced amphetamine reward was correlated with a transient increase in dendritic spines in the NAc. Next, a critical role for the transcription factor ΔFosB in sex experience-induced enhanced amphetamine reward and associated increases in dendritic spines on NAc neurons was established using viral vector gene transfer of the dominant-negative binding partner ΔJunD. Moreover, it was demonstrated that sexual experience-induced enhanced drug reward, ΔFosB, and spinogenesis are dependent on mating-induced dopamine D1 receptor activation in the NAc. Pharmacological blockade of D1 receptor, but not D2 receptor, in the NAc during sexual behavior attenuated ΔFosB induction and prevented increased spinogenesis and sensitized amphetamine reward. Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. PMID:23426671

  12. Dopamine-signalled reward predictions generated by competitive excitation and inhibition in a spiking neural network model

    Directory of Open Access Journals (Sweden)

    Paul eChorley

    2011-05-01

    Full Text Available Dopaminergic neurons in the mammalian substantia nigra displaycharacteristic phasic responses to stimuli which reliably predict thereceipt of primary rewards. These responses have been suggested toencode reward prediction-errors similar to those used in reinforcementlearning. Here, we propose a model of dopaminergic activity in whichprediction error signals are generated by the joint action ofshort-latency excitation and long-latency inhibition, in a networkundergoing dopaminergic neuromodulation of both spike-timing dependentsynaptic plasticity and neuronal excitability. In contrast toprevious models, sensitivity to recent events is maintained by theselective modification of specific striatal synapses, efferent tocortical neurons exhibiting stimulus-specific, temporally extendedactivity patterns. Our model shows, in the presence of significantbackground activity, (i a shift in dopaminergic response from rewardto reward predicting stimuli, (ii preservation of a response tounexpected rewards, and (iii a precisely-timed below-baseline dip inactivity observed when expected rewards are omitted.

  13. Nutritional controls of food reward.

    Science.gov (United States)

    Fernandes, Maria F; Sharma, Sandeep; Hryhorczuk, Cecile; Auguste, Stephanie; Fulton, Stephanie

    2013-08-01

    The propensity to select and consume palatable nutrients is strongly influenced by the rewarding effects of food. Neural processes integrating reward, emotional states and decision-making can supersede satiety signals to promote excessive caloric intake and weight gain. While nutritional habits are influenced by reward-based neural mechanisms, nutrition and its impact on energy metabolism, in turn, plays an important role in the control of food reward. Feeding modulates the release of metabolic hormones that have an important influence on central controls of appetite. Nutrients themselves are also an essential source of energy fuel, while serving as key metabolites and acting as signalling molecules in the neural pathways that control feeding and food reward. Along these lines, this review discusses the impact of nutritionally regulated hormones and select macronutrients on the behavioural and neural processes underlying the rewarding effects of food. Copyright © 2013 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  14. Willing to Wait: Elevated Reward-Processing EEG Activity Associated with a Greater Preference for Larger-But-Delayed Rewards

    OpenAIRE

    Pornpattananangkul, Narun; Nusslock, Robin

    2016-01-01

    While almost everyone discounts the value of future rewards over immediate rewards, people differ in their so-called delay-discounting. One of the several factors that may explain individual differences in delay-discounting is reward-processing. To study individual-differences in reward-processing, however, one needs to consider the heterogeneity of neural-activity at each reward-processing stage. Here using EEG, we separated reward-related neural activity into distinct reward-anticipation an...

  15. Modulatory effects of modafinil on neural circuits regulating emotion and cognition.

    Science.gov (United States)

    Rasetti, Roberta; Mattay, Venkata S; Stankevich, Beth; Skjei, Kelsey; Blasi, Giuseppe; Sambataro, Fabio; Arrillaga-Romany, Isabel C; Goldberg, Terry E; Callicott, Joseph H; Apud, José A; Weinberger, Daniel R

    2010-09-01

    Modafinil differs from other arousal-enhancing agents in chemical structure, neurochemical profile, and behavioral effects. Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition, but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior, too. We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions. Healthy volunteers were enrolled in this double-blinded placebo-controlled trial (100 mg/day for 7 days). They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks-a working memory (WM) task and a variable attentional control (VAC) task. A clinical assessment that included measurement of blood pressure, heart rate, the Hamilton anxiety scale, and the profile of mood state (POMS) questionnaire was also performed on each test day. BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition. During executive cognition tasks, a WM task and a VAC task, modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate. Although not statistically significant, there were trends for reduced anxiety, for decreased fatigue-inertia and increased vigor-activity, as well as decreased anger-hostility on modafinil. Modafinil in low doses has a unique physiologic profile compared with stimulant drugs: it enhances the efficiency of prefrontal cortical cognitive information processing, while dampening reactivity to threatening stimuli in the amygdala, a brain region implicated in anxiety.

  16. Modulatory Effects of Modafinil on Neural Circuits Regulating Emotion and Cognition

    Science.gov (United States)

    Rasetti, Roberta; Mattay, Venkata S; Stankevich, Beth; Skjei, Kelsey; Blasi, Giuseppe; Sambataro, Fabio; Arrillaga-Romany, Isabel C; Goldberg, Terry E; Callicott, Joseph H; Apud, José A; Weinberger, Daniel R

    2010-01-01

    Modafinil differs from other arousal-enhancing agents in chemical structure, neurochemical profile, and behavioral effects. Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition, but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior, too. We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions. Healthy volunteers were enrolled in this double-blinded placebo-controlled trial (100 mg/day for 7 days). They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks—a working memory (WM) task and a variable attentional control (VAC) task. A clinical assessment that included measurement of blood pressure, heart rate, the Hamilton anxiety scale, and the profile of mood state (POMS) questionnaire was also performed on each test day. BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition. During executive cognition tasks, a WM task and a VAC task, modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate. Although not statistically significant, there were trends for reduced anxiety, for decreased fatigue-inertia and increased vigor-activity, as well as decreased anger-hostility on modafinil. Modafinil in low doses has a unique physiologic profile compared with stimulant drugs: it enhances the efficiency of prefrontal cortical cognitive information processing, while dampening reactivity to threatening stimuli in the amygdala, a brain region implicated in anxiety. PMID:20555311

  17. Neural responses to various rewards and feedback in the brains of adolescent Internet addicts detected by functional magnetic resonance imaging.

    Science.gov (United States)

    Kim, Ji-Eun; Son, Jung-Woo; Choi, Won-Hee; Kim, Yeoung-Rang; Oh, Jong-Hyun; Lee, Seungbok; Kim, Jang-Kyu

    2014-06-01

    This study aimed to examine differences in brain activation for various types of reward and feedback in adolescent Internet addicts (AIA) and normal adolescents (NA) using functional magnetic resonance imaging (fMRI). AIA (n = 15) and NA (n = 15) underwent fMRI while performing easy tasks for which performance feedback (PF), social reward (SR) (such as compliments), or monetary reward (MR) was given. Using the no reward (NR) condition, three types of contrasts (PF-NR, SR-NR, and MR-NR) were analyzed. In NA, we observed activation in the reward-related subcortical system, self-related brain region, and other brain areas for the three contrasts, but these brain areas showed almost no activation in AIA. Instead, AIA showed significant activation in the dorsolateral prefrontal cortex for the PF-NR contrast and the negative correlation was found between the level of activation in the left superior temporal gyrus (BA 22) and the duration of Internet game use per day in AIA. These findings suggest that AIA show reduced levels of self-related brain activation and decreased reward sensitivity irrespective of the type of reward and feedback. AIA may be only sensitive to error monitoring regardless of positive feelings, such as sense of satisfaction or achievement. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  18. The Good, the Bad, and the Irrelevant: Neural Mechanisms of Learning Real and Hypothetical Rewards and Effort.

    Science.gov (United States)

    Scholl, Jacqueline; Kolling, Nils; Nelissen, Natalie; Wittmann, Marco K; Harmer, Catherine J; Rushworth, Matthew F S

    2015-08-12

    Natural environments are complex, and a single choice can lead to multiple outcomes. Agents should learn which outcomes are due to their choices and therefore relevant for future decisions and which are stochastic in ways common to all choices and therefore irrelevant for future decisions between options. We designed an experiment in which human participants learned the varying reward and effort magnitudes of two options and repeatedly chose between them. The reward associated with a choice was randomly real or hypothetical (i.e., participants only sometimes received the reward magnitude associated with the chosen option). The real/hypothetical nature of the reward on any one trial was, however, irrelevant for learning the longer-term values of the choices, and participants ought to have only focused on the informational content of the outcome and disregarded whether it was a real or hypothetical reward. However, we found that participants showed an irrational choice bias, preferring choices that had previously led, by chance, to a real reward in the last trial. Amygdala and ventromedial prefrontal activity was related to the way in which participants' choices were biased by real reward receipt. By contrast, activity in dorsal anterior cingulate cortex, frontal operculum/anterior insula, and especially lateral anterior prefrontal cortex was related to the degree to which participants resisted this bias and chose effectively in a manner guided by aspects of outcomes that had real and more sustained relationships with particular choices, suppressing irrelevant reward information for more optimal learning and decision making. In complex natural environments, a single choice can lead to multiple outcomes. Human agents should only learn from outcomes that are due to their choices, not from outcomes without such a relationship. We designed an experiment to measure learning about reward and effort magnitudes in an environment in which other features of the outcome were

  19. The Good, the Bad, and the Irrelevant: Neural Mechanisms of Learning Real and Hypothetical Rewards and Effort

    Science.gov (United States)

    Kolling, Nils; Nelissen, Natalie; Wittmann, Marco K.; Harmer, Catherine J.; Rushworth, Matthew F. S.

    2015-01-01

    Natural environments are complex, and a single choice can lead to multiple outcomes. Agents should learn which outcomes are due to their choices and therefore relevant for future decisions and which are stochastic in ways common to all choices and therefore irrelevant for future decisions between options. We designed an experiment in which human participants learned the varying reward and effort magnitudes of two options and repeatedly chose between them. The reward associated with a choice was randomly real or hypothetical (i.e., participants only sometimes received the reward magnitude associated with the chosen option). The real/hypothetical nature of the reward on any one trial was, however, irrelevant for learning the longer-term values of the choices, and participants ought to have only focused on the informational content of the outcome and disregarded whether it was a real or hypothetical reward. However, we found that participants showed an irrational choice bias, preferring choices that had previously led, by chance, to a real reward in the last trial. Amygdala and ventromedial prefrontal activity was related to the way in which participants' choices were biased by real reward receipt. By contrast, activity in dorsal anterior cingulate cortex, frontal operculum/anterior insula, and especially lateral anterior prefrontal cortex was related to the degree to which participants resisted this bias and chose effectively in a manner guided by aspects of outcomes that had real and more sustained relationships with particular choices, suppressing irrelevant reward information for more optimal learning and decision making. SIGNIFICANCE STATEMENT In complex natural environments, a single choice can lead to multiple outcomes. Human agents should only learn from outcomes that are due to their choices, not from outcomes without such a relationship. We designed an experiment to measure learning about reward and effort magnitudes in an environment in which other features

  20. Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity

    Science.gov (United States)

    Bennett, James E. M.; Bair, Wyeth

    2015-01-01

    Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli. PMID:26308406

  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. Influence of reward motivation on human declarative memory.

    Science.gov (United States)

    Miendlarzewska, Ewa A; Bavelier, Daphne; Schwartz, Sophie

    2016-02-01

    Motivational relevance can prioritize information for memory encoding and consolidation based on reward value. In this review, we pinpoint the possible psychological and neural mechanisms by which reward promotes learning, from guiding attention to enhancing memory consolidation. We then discuss how reward value can spill-over from one conditioned stimulus to a non-conditioned stimulus. Such generalization can occur across perceptually similar items or through more complex relations, such as associative or logical inferences. Existing evidence suggests that the neurotransmitter dopamine boosts the formation of declarative memory for rewarded information and may also control the generalization of reward values. In particular, temporally-correlated activity in the hippocampus and in regions of the dopaminergic circuit may mediate value-based decisions and facilitate cross-item integration. Given the importance of generalization in learning, our review points to the need to study not only how reward affects later memory but how learned reward values may generalize to related representations and ultimately alter memory structure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence.

    Science.gov (United States)

    Casement, Melynda D; Shaw, Daniel S; Sitnick, Stephanie L; Musselman, Samuel C; Forbes, Erika E

    2015-03-01

    Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  4. A neural circuit model of emotional learning using two pathways with different granularity and speed of information processing.

    Science.gov (United States)

    Murakoshi, Kazushi; Saito, Mayuko

    2009-02-01

    We propose a neural circuit model of emotional learning using two pathways with different granularity and speed of information processing. In order to derive a precise time process, we utilized a spiking model neuron proposed by Izhikevich and spike-timing-dependent synaptic plasticity (STDP) of both excitatory and inhibitory synapses. We conducted computer simulations to evaluate the proposed model. We demonstrate some aspects of emotional learning from the perspective of the time process. The agreement of the results with the previous behavioral experiments suggests that the structure and learning process of the proposed model are appropriate.

  5. The neural basis of decision-making and reward processing in adults with euthymic bipolar disorder or attention-deficit/hyperactivity disorder (ADHD.

    Directory of Open Access Journals (Sweden)

    Agustin Ibanez

    Full Text Available BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD and bipolar disorder (BD share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD. METHODOLOGY/PRINCIPAL FINDINGS: We used the Iowa gambling task (IGT, a task of rational decision-making under risk (RDMUR and a rapid-decision gambling task (RDGT which elicits behavioral measures as well as event-related potentials (ERPs: fERN and P3 in connection to the motivational impact of events. We did not observe between-group differences for decision-making under risk or ambiguity (RDMUR and IGT; however, there were significant differences for the ERP-assessed RDGT. Compared to controls, the ADHD group showed a pattern of impaired learning by feedback (fERN and insensitivity to reward magnitude (P3. This ERP pattern (fERN and P3 was associated with impulsivity, hyperactivity, executive function and working memory. Compared to controls, the BD group showed fERN- and P3-enhanced responses to reward magnitude regardless of valence. This ERP pattern (fERN and P3 was associated with mood and inhibitory control. Consistent with the ERP findings, an analysis of source location revealed reduced responses of the cingulate cortex to the valence and magnitude of rewards in patients with ADHD and BD. CONCLUSIONS/SIGNIFICANCE: Our data suggest that neurophysiological (ERPs paradigms such as the RDGT are well suited to assess subclinical decision-making processes in patients with ADHD and BD as well as for linking the cingulate cortex with action monitoring systems.

  6. Modification of tenascin-R expression following unilateral labyrinthectomy in rats indicates its possible role in neural plasticity of the vestibular neural circuit.

    Science.gov (United States)

    Gaal, Botond; Jóhannesson, Einar Örn; Dattani, Amit; Magyar, Agnes; Wéber, Ildikó; Matesz, Clara

    2015-09-01

    We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subsequent reorganization of extracellular matrix assembly correlates to the restoration of impaired vestibular function. The tenascin-R has repelling effect on pathfinding during axonal growth/regrowth, and thus inhibits neural circuit repair. By using immunohistochemical method, we studied the modification of tenascin-R expression in the superior, medial, lateral, and descending vestibular nuclei of the rat following unilateral labyrinthectomy. On postoperative day 1, tenascin-R reaction in the perineuronal nets disappeared on the side of labyrinthectomy in the superior, lateral, medial, and rostral part of the descending vestibular nuclei. On survival day 3, the staining intensity of tenascin-R reaction in perineuronal nets recovered on the operated side of the medial vestibular nucleus, whereas it was restored by the time of postoperative day 7 in the superior, lateral and rostral part of the descending vestibular nuclei. The staining intensity of tenascin-R reaction remained unchanged in the caudal part of the descending vestibular nucleus bilaterally. Regional differences in the modification of tenascin-R expression presented here may be associated with different roles of individual vestibular nuclei in the compensatory processes. The decreased expression of the tenascin-R may suggest the extracellular facilitation of plastic modifications in the vestibular neural circuit after lesion of the labyrinthine receptors.

  7. The link between callous-unemotional traits and neural mechanisms of reward processing : An fMRI study

    NARCIS (Netherlands)

    Veroude, Kim; von Rhein, Daniel; Chauvin, Roselyne J. M.; van Dongen, Eelco V.; Mennes, Maarten J. J.; Franke, Barbara; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Hartman, Catharina A.; Hoekstra, Pieter J.; Glennon, Jeffrey C.; Buitelaar, Jan K.

    2016-01-01

    Callous-unemotional (CU) traits, i.e., unconcernedness and lack of prosocial feelings, may manifest in Conduct Disorder (CD), but also in Oppositional Defiant Disorder (ODD) and Attention Deficit Hyperactivity Disorder (ADHD). These disorders have been associated with aberrant reward processing,

  8. An integrated multichannel neural recording analog front-end ASIC with area-efficient driven right leg circuit.

    Science.gov (United States)

    Tao Tang; Wang Ling Goh; Lei Yao; Jia Hao Cheong; Yuan Gao

    2017-07-01

    This paper describes an integrated multichannel neural recording analog front end (AFE) with a novel area-efficient driven right leg (DRL) circuit to improve the system common mode rejection ratio (CMRR). The proposed AFE consists of an AC-coupled low-noise programmable-gain amplifier, an area-efficient DRL block and a 10-bit SAR ADC. Compared to conventional DRL circuit, the proposed capacitor-less DRL design achieves 90% chip area reduction with enhanced CMRR performance, making it ideal for multichannel biomedical recording applications. The AFE circuit has been designed in a standard 0.18-μm CMOS process. Post-layout simulation results show that the AFE provides two gain settings of 54dB/60dB while consuming 1 μA per channel under a supply voltage of 1 V. The input-referred noise of the AFE integrated from 1 Hz to 10k Hz is only 4 μVrms and the CMRR is 110 dB.

  9. Neural circuits of disgust induced by sexual stimuli in homosexual and heterosexual men: An fMRI study

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Minming [Department of Radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Hu Shaohua [Department of Mental Health, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, Zhejiang Province 310003 (China); Xu Lijuan [National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing (China); Wang Qidong [Department of Radiology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Xu Xiaojun [Department of Radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Wei Erqing [College of Pharmacology, Zhejiang University (China); Yan Leqin [MD Anderson Cancer Center, Virginia Harris Cockrell Cancer Research Center, University of Texas, Austin (United States); Hu Jianbo; Wei Ning; Zhou Weihua; Huang Manli [Department of Mental Health, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, Zhejiang Province 310003 (China); Xu Yi, E-mail: xuyi61@yahoo.com.cn [Department of Mental Health, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, Zhejiang Province 310003 (China)

    2011-11-15

    Few studies demonstrated neural circuits related to disgust were influenced by internal sexual orientation in male. Here we used fMRI to study the neural responses to disgust in homosexual and heterosexual men to investigate that issue. Thirty-two healthy male volunteers (sixteen homosexual and sixteen heterosexual) were scanned while viewing alternating blocks of three types of erotic film: heterosexual couples (F-M), male homosexual couples (M-M), and female homosexual couples (F-F) engaged in sexual activity. All the participants rated their level of disgust and sexual arousal as well. The F-F and M-M stimuli induced disgust in homosexual and heterosexual men, respectively. The common activations related to disgusting stimuli included: bilateral frontal gyrus and occipital gyrus, right middle temporal gyrus, left superior temporal gyrus, right cerebellum, and right thalamus. Homosexual men had greater neural responses in the left medial frontal gyrus than did heterosexual men to the sexual disgusting stimuli; in contrast, heterosexual men showed significantly greater activation than homosexual men in the left cuneus. ROI analysis showed that negative correlation were found between the magnitude of MRI signals in the left medial frontal gyrus and scores of disgust in homosexual subjects (p < 0.05). This study indicated that there were regions in common as well as regions specific for each type of erotic stimuli during disgust of homosexual and heterosexual men.

  10. Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia.

    Science.gov (United States)

    Crabtree, Gregg W; Gogos, Joseph A

    2014-01-01

    Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point toward a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders (ASDs) may be due to a combination of both short-term and long-term synaptic plasticity alterations.

  11. States versus Rewards: Dissociable Neural Prediction Error Signals Underlying Model-Based and Model-Free Reinforcement Learning

    OpenAIRE

    Gläscher, Jan; Daw, Nathaniel; Dayan, Peter; O'Doherty, John P.

    2010-01-01

    Reinforcement learning (RL) uses sequential experience with situations (“states”) and outcomes to assess actions. Whereas model-free RL uses this experience directly, in the form of a reward prediction error (RPE), model-based RL uses it indirectly, building a model of the state transition and outcome structure of the environment, and evaluating actions by searching this model. A state prediction error (SPE) plays a central role, reporting discrepancies between the current model and the obser...

  12. A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia.

    Science.gov (United States)

    Lu, Yan; Dong, Hailong; Gao, Yandong; Gong, Yuanyuan; Ren, Yingna; Gu, Nan; Zhou, Shudi; Xia, Nan; Sun, Yan-Yan; Ji, Ru-Rong; Xiong, Lize

    2013-09-01

    Neuropathic pain is characterized by mechanical allodynia induced by low-threshold myelinated Aβ-fiber activation. The original gate theory of pain proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn (DH) act as "gate control" units for preventing the interaction between innocuous and nociceptive signals. However, our understanding of the neuronal circuits underlying pain signaling and modulation in the spinal DH is incomplete. Using a rat model, we have shown that the convergence of glycinergic inhibitory and excitatory Aβ-fiber inputs onto PKCγ+ neurons in the superficial DH forms a feed-forward inhibitory circuit that prevents Aβ input from activating the nociceptive pathway. This feed-forward inhibition was suppressed following peripheral nerve injury or glycine blockage, leading to inappropriate induction of action potential outputs in the nociceptive pathway by Aβ-fiber stimulation. Furthermore, spinal blockage of glycinergic synaptic transmission in vivo induced marked mechanical allodynia. Our findings identify a glycinergic feed-forward inhibitory circuit that functions as a gate control to separate the innocuous mechanoreceptive pathway and the nociceptive pathway in the spinal DH. Disruption of this glycinergic inhibitory circuit after peripheral nerve injury has the potential to elicit mechanical allodynia, a cardinal symptom of neuropathic pain.

  13. Analysis of the function and intracellular signal transduction mechanism of secreted semaphorins during neural circuit development

    NARCIS (Netherlands)

    Gunput, R.F.

    2011-01-01

    Our ability to perceive, to act and to remember is a reflection of the elaborate synaptic connections and neuronal circuits that make up the brain. The formation of these connections relies on a series of developmental events including axon growth and guidance, synapse formation and cell death. The

  14. Reward Dysfunction in the Manic Spectrum: Unable to Win? The Use of Biographical Information to Refine Neurobiological Modeling.

    Science.gov (United States)

    Gottlieb, John F

    2017-11-01

    The manic spectrum is thought to be characterized by a hypersensitive biobehavioral reward system, the behavioral activation system. Evidence for this framework comes from questionnaire-based, self-report data collected in cross-sectional and prospective studies of mania, mania in remission, and proneness to hypomania, and from functional neuroimaging investigations of brain reward circuit activity during incentivized choice protocols. Although heightened reward anticipation is consistently documented, the status of later goal attainment activity, hedonic responses, and satiety reactions is less clear. This report examines the status of such reward receipt processes as they operate in the manic spectrum. A case report of a typical subject with bipolar II disorder with a hyperthymic temperament is presented using longitudinal, biographical data. Diminished reward receipt, pleasure, and satiety were demonstrated indicating impaired hedonic processing in hyperthymic temperament. This impairment indicates a dissociation between early, intensified reward pursuit processes and later, blunted, reward attainment activity. The experience and neural correlates of hedonic processing may be impaired in the manic spectrum. Possible mechanisms for this impairment and its dissociation from the earlier stage of reward processing characterized by hyperactive reward pursuit are considered. Clinical reports and longitudinal, life-based follow-up can provide important data to supplement more experimentally based neurobiological models of reward dysfunction in bipolar disorders.

  15. 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.

  16. Effects of ion channel noise on neural circuits: an application to the respiratory pattern generator to investigate breathing variability.

    Science.gov (United States)

    Yu, Haitao; Dhingra, Rishi R; Dick, Thomas E; Galán, Roberto F

    2017-01-01

    Neural activity generally displays irregular firing patterns even in circuits with apparently regular outputs, such as motor pattern generators, in which the output frequency fluctuates randomly around a mean value. This "circuit noise" is inherited from the random firing of single neurons, which emerges from stochastic ion channel gating (channel noise), spontaneous neurotransmitter release, and its diffusion and binding to synaptic receptors. Here we demonstrate how to expand conductance-based network models that are originally deterministic to include realistic, physiological noise, focusing on stochastic ion channel gating. We illustrate this procedure with a well-established conductance-based model of the respiratory pattern generator, which allows us to investigate how channel noise affects neural dynamics at the circuit level and, in particular, to understand the relationship between the respiratory pattern and its breath-to-breath variability. We show that as the channel number increases, the duration of inspiration and expiration varies, and so does the coefficient of variation of the breath-to-breath interval, which attains a minimum when the mean duration of expiration slightly exceeds that of inspiration. For small channel numbers, the variability of the expiratory phase dominates over that of the inspiratory phase, and vice versa for large channel numbers. Among the four different cell types in the respiratory pattern generator, pacemaker cells exhibit the highest sensitivity to channel noise. The model shows that suppressing input from the pons leads to longer inspiratory phases, a reduction in breathing frequency, and larger breath-to-breath variability, whereas enhanced input from the raphe nucleus increases breathing frequency without changing its pattern. A major source of noise in neuronal circuits is the "flickering" of ion currents passing through the neurons' membranes (channel noise), which cannot be suppressed experimentally. Computational

  17. Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations.

    Science.gov (United States)

    Lichtenberg, Nina T; Pennington, Zachary T; Holley, Sandra M; Greenfield, Venuz Y; Cepeda, Carlos; Levine, Michael S; Wassum, Kate M

    2017-08-30

    To make an appropriate decision, one must anticipate potential future rewarding events, even when they are not readily observable. These expectations are generated by using observable information (e.g., stimuli or available actions) to retrieve often quite detailed memories of available rewards. The basolateral amygdala (BLA) and orbitofrontal cortex (OFC) are two reciprocally connected key nodes in the circuitry supporting such outcome-guided behaviors. But there is much unknown about the contribution of this circuit to decision making, and almost nothing known about the whether any contribution is via direct, monosynaptic projections, or the direction of information transfer. Therefore, here we used designer receptor-mediated inactivation of OFC→BLA or BLA→OFC projections to evaluate their respective contributions to outcome-guided behaviors in rats. Inactivation of BLA terminals in the OFC, but not OFC terminals in the BLA, disrupted the selective motivating influence of cue-triggered reward representations over reward-seeking decisions as assayed by Pavlovian-to-instrumental transfer. BLA→OFC projections were also required when a cued reward representation was used to modify Pavlovian conditional goal-approach responses according to the reward's current value. These projections were not necessary when actions were guided by reward expectations generated based on learned action-reward contingencies, or when rewards themselves, rather than stored memories, directed action. These data demonstrate that BLA→OFC projections enable the cue-triggered reward expectations that can motivate the execution of specific action plans and allow adaptive conditional responding.SIGNIFICANCE STATEMENT Deficits anticipating potential future rewarding events are associated with many psychiatric diseases. Presently, we know little about the neural circuits supporting such reward expectation. Here we show that basolateral amygdala to orbitofrontal cortex projections are

  18. A Neural Circuit for Acoustic Navigation combining Heterosynaptic and Non-synaptic Plasticity that learns Stable Trajectories

    DEFF Research Database (Denmark)

    Shaikh, Danish; Manoonpong, Poramate

    2017-01-01

    Reactive spatial robot navigation in goal-directed tasks such as phonotaxis requires generating consistent and stable trajectories towards an acoustic target while avoiding obstacles. High-level goal-directed steering behaviour can steer a robot towards the target by mapping sound direction...... controllers be resolved in a manner that generates consistent and stable robot trajectories? We propose a neural circuit that minimises this conflict by learning sensorimotor mappings as neuronal transfer functions between the perceived sound direction and wheel velocities of a simulated non-holonomic mobile...... robot. These mappings constitute the high-level goal-directed steering behaviour. Sound direction information is obtained from a model of the lizard peripheral auditory system. The parameters of the transfer functions are learned via an online unsupervised correlation learning algorithm through...

  19. Next-generation transgenic mice for optogenetic analysis of neural circuits

    Directory of Open Access Journals (Sweden)

    Brent eAsrican

    2013-11-01

    Full Text Available Here we characterize several new lines of transgenic mice useful for optogenetic analysis of brain circuit function. These mice express optogenetic probes, such as enhanced halorhodopsin or several different versions of channelrhodopsins, behind various neuron-specific promoters. These mice permit photoinhibition or photostimulation both in vitro and in vivo. Our results also reveal the important influence of fluorescent tags on optogenetic probe expression and function in transgenic mice.

  20. Rules and mechanisms for efficient two-stage learning in neural circuits.

    Science.gov (United States)

    Teşileanu, Tiberiu; Ölveczky, Bence; Balasubramanian, Vijay

    2017-04-04

    Trial-and-error learning requires evaluating variable actions and reinforcing successful variants. In songbirds, vocal exploration is induced by LMAN, the output of a basal ganglia-related circuit that also contributes a corrective bias to the vocal output. This bias is gradually consolidated in RA, a motor cortex analogue downstream of LMAN. We develop a new model of such two-stage learning. Using stochastic gradient descent, we derive how the activity in 'tutor' circuits ( e.g., LMAN) should match plasticity mechanisms in 'student' circuits ( e.g., RA) to achieve efficient learning. We further describe a reinforcement learning framework through which the tutor can build its teaching signal. We show that mismatches between the tutor signal and the plasticity mechanism can impair learning. Applied to birdsong, our results predict the temporal structure of the corrective bias from LMAN given a plasticity rule in RA. Our framework can be applied predictively to other paired brain areas showing two-stage learning.

  1. Fluorescence-based monitoring of in vivo neural activity using a circuit-tracing pseudorabies virus.

    Directory of Open Access Journals (Sweden)

    Andrea E Granstedt

    Full Text Available The study of coordinated activity in neuronal circuits has been challenging without a method to simultaneously report activity and connectivity. Here we present the first use of pseudorabies virus (PRV, which spreads through synaptically connected neurons, to express a fluorescent calcium indicator protein and monitor neuronal activity in a living animal. Fluorescence signals were proportional to action potential number and could reliably detect single action potentials in vitro. With two-photon imaging in vivo, we observed both spontaneous and stimulated activity in neurons of infected murine peripheral autonomic submandibular ganglia (SMG. We optically recorded the SMG response in the salivary circuit to direct electrical stimulation of the presynaptic axons and to physiologically relevant sensory stimulation of the oral cavity. During a time window of 48 hours after inoculation, few spontaneous transients occurred. By 72 hours, we identified more frequent and prolonged spontaneous calcium transients, suggestive of neuronal or tissue responses to infection that influence calcium signaling. Our work establishes in vivo investigation of physiological neuronal circuit activity and subsequent effects of infection with single cell resolution.

  2. Evolution and analysis of minimal neural circuits for klinotaxis in Caenorhabditis elegans.

    Science.gov (United States)

    Izquierdo, Eduardo J; Lockery, Shawn R

    2010-09-29

    Chemotaxis during sinusoidal locomotion in nematodes captures in simplified form the general problem of how dynamical interactions between the nervous system, body, and environment are exploited in the generation of adaptive behavior. We used an evolutionary algorithm to generate neural networks that exhibit klinotaxis, a common form of chemotaxis in which the direction of locomotion in a chemical gradient closely follows the line of steepest ascent. Sensory inputs and motor outputs of the model networks were constrained to match the inputs and outputs of the Caenorhabditis elegans klinotaxis network. We found that a minimalistic neural network, comprised of an ON-OFF pair of chemosensory neurons and a pair of neck muscle motor neurons, is sufficient to generate realistic klinotaxis behavior. Importantly, emergent properties of model networks reproduced two key experimental observations that they were not designed to fit, suggesting that the model may be operating according to principles similar to those of the biological network. A dynamical systems analysis of 77 evolved networks revealed a novel neural mechanism for spatial orientation behavior. This mechanism provides a testable hypothesis that is likely to accelerate the discovery and analysis of the biological circuitry for chemotaxis in C. elegans.

  3. A multichannel integrated circuit for electrical recording of neural activity, with independent channel programmability.

    Science.gov (United States)

    Mora Lopez, Carolina; Prodanov, Dimiter; Braeken, Dries; Gligorijevic, Ivan; Eberle, Wolfgang; Bartic, Carmen; Puers, Robert; Gielen, Georges

    2012-04-01

    Since a few decades, micro-fabricated neural probes are being used, together with microelectronic interfaces, to get more insight in the activity of neuronal networks. The need for higher temporal and spatial recording resolutions imposes new challenges on the design of integrated neural interfaces with respect to power consumption, data handling and versatility. In this paper, we present an integrated acquisition system for in vitro and in vivo recording of neural activity. The ASIC consists of 16 low-noise, fully-differential input channels with independent programmability of its amplification (from 100 to 6000 V/V) and filtering (1-6000 Hz range) capabilities. Each channel is AC-coupled and implements a fourth-order band-pass filter in order to steeply attenuate out-of-band noise and DC input offsets. The system achieves an input-referred noise density of 37 nV/√Hz, a NEF of 5.1, a CMRR > 60 dB, a THD noise ratios.

  4. The Physics of Decision Making:. Stochastic Differential Equations as Models for Neural Dynamics and Evidence Accumulation in Cortical Circuits

    Science.gov (United States)

    Holmes, Philip; Eckhoff, Philip; Wong-Lin, K. F.; Bogacz, Rafal; Zacksenhouse, Miriam; Cohen, Jonathan D.

    2010-03-01

    We describe how drift-diffusion (DD) processes - systems familiar in physics - can be used to model evidence accumulation and decision-making in two-alternative, forced choice tasks. We sketch the derivation of these stochastic differential equations from biophysically-detailed models of spiking neurons. DD processes are also continuum limits of the sequential probability ratio test and are therefore optimal in the sense that they deliver decisions of specified accuracy in the shortest possible time. This leaves open the critical balance of accuracy and speed. Using the DD model, we derive a speed-accuracy tradeoff that optimizes reward rate for a simple perceptual decision task, compare human performance with this benchmark, and discuss possible reasons for prevalent sub-optimality, focussing on the question of uncertain estimates of key parameters. We present an alternative theory of robust decisions that allows for uncertainty, and show that its predictions provide better fits to experimental data than a more prevalent account that emphasises a commitment to accuracy. The article illustrates how mathematical models can illuminate the neural basis of cognitive processes.

  5. Neural reuse of action perception circuits for language, concepts and communication.

    Science.gov (United States)

    Pulvermüller, Friedemann

    2018-01-01

    Neurocognitive and neurolinguistics theories make explicit statements relating specialized cognitive and linguistic processes to specific brain loci. These linking hypotheses are in need of neurobiological justification and explanation. Recent mathematical models of human language mechanisms constrained by fundamental neuroscience principles and established knowledge about comparative neuroanatomy offer explanations for where, when and how language is processed in the human brain. In these models, network structure and connectivity along with action- and perception-induced correlation of neuronal activity co-determine neurocognitive mechanisms. Language learning leads to the formation of action perception circuits (APCs) with specific distributions across cortical areas. Cognitive and linguistic processes such as speech production, comprehension, verbal working memory and prediction are modelled by activity dynamics in these APCs, and combinatorial and communicative-interactive knowledge is organized in the dynamics within, and connections between APCs. The network models and, in particular, the concept of distributionally-specific circuits, can account for some previously not well understood facts about the cortical 'hubs' for semantic processing and the motor system's role in language understanding and speech sound recognition. A review of experimental data evaluates predictions of the APC model and alternative theories, also providing detailed discussion of some seemingly contradictory findings. Throughout, recent disputes about the role of mirror neurons and grounded cognition in language and communication are assessed critically. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  6. Normalization of Intrinsic Neural Circuits Governing Tourette's Syndrome Using Cranial Electrotherapy Stimulation.

    Science.gov (United States)

    Qiao, Jianping; Weng, Shenhong; Wang, Pengwei; Long, Jun; Wang, Zhishun

    2015-05-01

    The aim of this study was to investigate the normalization of the intrinsic functional activity and connectivity of TS adolescents before and after the cranial electrotherapy stimulation (CES) with alpha stim device. We performed resting-state functional magnetic resonance imaging on eight adolescents before and after CES with mean age of about nine-years old who had Tourette's syndrome with moderate to severe tics symptom. Independent component analysis (ICA) with hierarchical partner matching method was used to examine the functional connectivity between regions within cortico-striato-thalamo-cortical (CSTC) circuit. Granger causality was used to investigate effective connectivity among these regions detected by ICA. We then performed pattern classification on independent components with significant group differences that served as endophenotype markers to distinguish the adolescents between TS and the normalized ones after CES. Results showed that TS adolescents after CES treatment had stronger functional activity and connectivity in anterior cingulate cortex (ACC), caudate and posterior cingulate cortex while had weaker activity in supplementary motor area within the motor pathway compared with TS before CES. The results suggest that the functional activity and connectivity in motor pathway was suppressed while activities in the control portions within CSTC loop including ACC and caudate were increased in TS adolescents after CES compared with adolescents before CES. The normalization of the balance between motor and control portions of the CSTC circuit may result in the recovery of TS adolescents.

  7. The decision to engage cognitive control is driven by expected reward-value: neural and behavioral evidence.

    Directory of Open Access Journals (Sweden)

    Matthew L Dixon

    Full Text Available Cognitive control is a fundamental skill reflecting the active use of task-rules to guide behavior and suppress inappropriate automatic responses. Prior work has traditionally used paradigms in which subjects are told when to engage cognitive control. Thus, surprisingly little is known about the factors that influence individuals' initial decision of whether or not to act in a reflective, rule-based manner. To examine this, we took three classic cognitive control tasks (Stroop, Wisconsin Card Sorting Task, Go/No-Go task and created novel 'free-choice' versions in which human subjects were free to select an automatic, pre-potent action, or an action requiring rule-based cognitive control, and earned varying amounts of money based on their choices. Our findings demonstrated that subjects' decision to engage cognitive control was driven by an explicit representation of monetary rewards expected to be obtained from rule-use. Subjects rarely engaged cognitive control when the expected outcome was of equal or lesser value as compared to the value of the automatic response, but frequently engaged cognitive control when it was expected to yield a larger monetary outcome. Additionally, we exploited fMRI-adaptation to show that the lateral prefrontal cortex (LPFC represents associations between rules and expected reward outcomes. Together, these findings suggest that individuals are more likely to act in a reflective, rule-based manner when they expect that it will result in a desired outcome. Thus, choosing to exert cognitive control is not simply a matter of reason and willpower, but rather, conforms to standard mechanisms of value-based decision making. Finally, in contrast to current models of LPFC function, our results suggest that the LPFC plays a direct role in representing motivational incentives.

  8. A low-power, low-noise neural-signal amplifier circuit in 90-nm CMOS.

    Science.gov (United States)

    Zarifi, M H; Frounchi, J; Farshchi, S; Judy, J W

    2008-01-01

    A fully-differential low-power low-noise preamplifier for biopotential and neural-recording applications is presented. This design, which has been simulated in a standard 90-nm CMOS process, consumes 30 microW from a 3-V power supply. The simulated integrated input-referred noise is 2.3 microV over 0.1 Hz to 20 kHz. The amplifier also provides an output swing of +/- 0.9 V with a THD of less than 0.1%

  9. Negative emotional distraction on neural circuits for working memory in patients with posttraumatic stress disorder.

    Science.gov (United States)

    Zhang, Jing-na; Xiong, Kun-lining; Qiu, Ming-guo; Zhang, Ye; Xie, Bing; Wang, Jian; Li, Min; Chen, Han; Zhang, Yu; Zhang, Jia-jia

    2013-09-19

    To study the neural mechanism for the impact of negative emotional distraction on working memory in patients with posttraumatic stress disorder (PTSD) resulting from exposure to motor vehicle accidents. Twenty PTSD patients and 20 healthy subjects were recruited. Event-related functional magnetic resonance imaging (fMRI) was used to investigate the effects of negative and neutral distractors on a delayed-response working memory task. All experiments were performed on a 3.0T MRI scanner, and the functional imaging data were analyzed using SPM8 software. The PTSD group showed poorer performance than the control group when the negative distractors were presented during the delay phase of working memory. The functional imaging indicated that, in the presence of negative relative to neutral distractors, the PTSD group showed higher activation in the emotion processing regions, including amygdala, precuneus and fusiform gyrus, but lower activation in the inferior frontal cortex, insula and left supramarginal gyrus than the control group. Based on the results that activation in the PTSD patients in the presence of negative distractors increased in the emotion-related brain regions but decreased in the working memory-related brain regions, we may conclude that the neural basis of working memory is impaired by negative emotion in PTSD patients. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Neural circuits in anxiety and stress disorders: a focused review

    Directory of Open Access Journals (Sweden)

    Duval ER

    2015-01-01

    Full Text Available Elizabeth R Duval, Arash Javanbakht, Israel LiberzonDepartment of Psychiatry, University of Michigan Health System, Ann Arbor, MI, USAAbstract: Anxiety and stress disorders are among the most prevalent neuropsychiatric disorders. In recent years, multiple studies have examined brain regions and networks involved in anxiety symptomatology in an effort to better understand the mechanisms involved and to develop more effective treatments. However, much remains unknown regarding the specific abnormalities and interactions between networks of regions underlying anxiety disorder presentations. We examined recent neuroimaging literature that aims to identify neural mechanisms underlying anxiety, searching for patterns of neural dysfunction that might be specific to different anxiety disorder categories. Across different anxiety and stress disorders, patterns of hyperactivation in emotion-generating regions and hypoactivation in prefrontal/regulatory regions are common in the literature. Interestingly, evidence of differential patterns is also emerging, such that within a spectrum of disorders ranging from more fear-based to more anxiety-based, greater involvement of emotion-generating regions is reported in panic disorder and specific phobia, and greater involvement of prefrontal regions is reported in generalized anxiety disorder and posttraumatic stress disorder. We summarize the pertinent literature and suggest areas for continued investigation.Keywords: fear, anxiety, neuroimaging

  11. PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans.

    Science.gov (United States)

    Barrios, Arantza; Ghosh, Rajarshi; Fang, Chunhui; Emmons, Scott W; Barr, Maureen M

    2012-12-01

    Appetitive behaviors require complex decision making that involves the integration of environmental stimuli and physiological needs. C. elegans mate searching is a male-specific exploratory behavior regulated by two competing needs: food and reproductive appetite. We found that the pigment dispersing factor receptor (PDFR-1) modulates the circuit that encodes the male reproductive drive that promotes male exploration following mate deprivation. PDFR-1 and its ligand, PDF-1, stimulated mate searching in the male, but not in the hermaphrodite. pdf-1 was required in the gender-shared interneuron AIM, and the receptor acted in internal and external environment-sensing neurons of the shared nervous system (URY, PQR and PHA) to produce mate-searching behavior. Thus, the pdf-1 and pdfr-1 pathway functions in non-sex-specific neurons to produce a male-specific, goal-oriented exploratory behavior. Our results indicate that secretin neuropeptidergic signaling is involved in regulating motivational internal states.

  12. SEMICONDUCTOR INTEGRATED CIRCUITS: A four-channel microelectronic system for neural signal regeneration

    Science.gov (United States)

    Shushan, Xie; Zhigong, Wang; Xiaoying, Lü; Wenyuan, Li; Haixian, Pan

    2009-12-01

    This paper presents a microelectronic system which is capable of making a signal record and functional electric stimulation of an injured spinal cord. As a requirement of implantable engineering for the regeneration microelectronic system, the system is of low noise, low power, small size and high performance. A front-end circuit and two high performance OPAs (operational amplifiers) have been designed for the system with different functions, and the two OPAs are a low-noise low-power two-stage OPA and a constant-gm RTR input and output OPA. The system has been realized in CSMC 0.5-μm CMOS technology. The test results show that the system satisfies the demands of neuron signal regeneration.

  13. Neural correlates of side-specific odour memory in mushroom body output neurons.

    Science.gov (United States)

    Strube-Bloss, Martin F; Nawrot, Martin P; Menzel, Randolf

    2016-12-14

    Humans and other mammals as well as honeybees learn a unilateral association between an olfactory stimulus presented to one side and a reward. In all of them, the learned association can be behaviourally retrieved via contralateral stimulation, suggesting inter-hemispheric communication. However, the underlying neuronal circuits are largely unknown and neural correlates of across-brain-side plasticity have yet not been demonstrated. We report neural plasticity that reflects lateral integration after side-specific odour reward conditioning. Mushroom body output neurons that did not respond initially to contralateral olfactory stimulation developed a unique and stable representation of the rewarded compound stimulus (side and odour) predicting its value during memory retention. The encoding of the reward-associated compound stimulus is delayed by about 40 ms compared with unrewarded neural activity, indicating an increased computation time for the read-out after lateral integration. © 2016 The Author(s).

  14. Neural circuits in the brain that are activated when mitigating criminal sentences.

    Science.gov (United States)

    Yamada, Makiko; Camerer, Colin F; Fujie, Saori; Kato, Motoichiro; Matsuda, Tetsuya; Takano, Harumasa; Ito, Hiroshi; Suhara, Tetsuya; Takahashi, Hidehiko

    2012-03-27

    In sentencing guilty defendants, jurors and judges weigh 'mitigating circumstances', which create sympathy for a defendant. Here we use functional magnetic resonance imaging to measure neural activity in ordinary citizens who are potential jurors, as they decide on mitigation of punishment for murder. We found that sympathy activated regions associated with mentalising and moral conflict (dorsomedial prefrontal cortex, precuneus and temporo-parietal junction). Sentencing also activated precuneus and anterior cingulate cortex, suggesting that mitigation is based on negative affective responses to murder, sympathy for mitigating circumstances and cognitive control to choose numerical punishments. Individual differences on the inclination to mitigate, the sentence reduction per unit of judged sympathy, correlated with activity in the right middle insula, an area known to represent interoception of visceral states. These results could help the legal system understand how potential jurors actually decide, and contribute to growing knowledge about whether emotion and cognition are integrated sensibly in difficult judgments.

  15. Altered neural connectivity in excitatory and inhibitory cortical circuits in autism

    Directory of Open Access Journals (Sweden)

    Basilis eZikopoulos

    2013-09-01

    Full Text Available Converging evidence from diverse studies suggests that atypical brain connectivity in autism affects in distinct ways short- and long-range cortical pathways, disrupting neural communication and the balance of excitation and inhibition. This hypothesis is based mostly on functional non-invasive studies that show atypical synchronization and connectivity patterns between cortical areas in children and adults with autism. Indirect methods to study the course and integrity of major brain pathways at low resolution show changes in fractional anisotropy or diffusivity of the white matter in autism. Findings in post-mortem brains of adults with autism provide evidence of changes in the fine structure of axons below prefrontal cortices, which communicate over short- or long-range pathways with other cortices and subcortical structures. Here we focus on evidence of cellular and axon features that likely underlie the changes in short- and long-range communication in autism. We review recent findings of changes in the shape, thickness, and volume of brain areas, cytoarchitecture, neuronal morphology, cellular elements, and structural and neurochemical features of individual axons in the white matter, where pathology is evident even in gross images. We relate cellular and molecular features to imaging and genetic studies that highlight a variety of polymorphisms and epigenetic factors that primarily affect neurite growth and synapse formation and function in autism. We report preliminary findings of changes in autism in the ratio of distinct types of inhibitory neurons in prefrontal cortex, known to shape network dynamics and the balance of excitation and inhibition. Finally we present a model that synthesizes diverse findings by relating them to developmental events, with a goal to identify common processes that perturb development in autism and affect neural communication, reflected in altered patterns of attention, social interactions, and language.

  16. Neural circuit of verbal humor comprehension in schizophrenia - an fMRI study

    Directory of Open Access Journals (Sweden)

    Przemysław Adamczyk

    2017-01-01

    Full Text Available Individuals with schizophrenia exhibit problems with understanding the figurative meaning of language. This study evaluates neural correlates of diminished humor comprehension observed in schizophrenia. The study included chronic schizophrenia (SCH outpatients (n = 20, and sex, age and education level matched healthy controls (n = 20. The fMRI punchline based humor comprehension task consisted of 60 stories of which 20 had funny, 20 nonsensical and 20 neutral (not funny punchlines. After the punchlines were presented, the participants were asked to indicate whether the story was comprehensible and how funny it was. Three contrasts were analyzed in both groups reflecting stages of humor processing: abstract vs neutral stories - incongruity detection; funny vs abstract - incongruity resolution and elaboration; and funny vs neutral – complete humor processing. Additionally, parametric modulation analysis was performed using both subjective ratings separately. Between-group comparisons revealed that the SCH subjects had attenuated activation in the right posterior superior temporal gyrus (BA 41 in case of irresolvable incongruity processing of nonsensical puns; in the left dorsomedial middle and superior frontal gyri (BA 8/9 in case of incongruity resolution and elaboration processing of funny puns; and in the interhemispheric dorsal anterior cingulate cortex (BA 24 in case of complete processing of funny puns. Additionally, during comprehensibility ratings the SCH group showed a suppressed activity in the left dorsomedial middle and superior frontal gyri (BA 8/9 and revealed weaker activation during funniness ratings in the left dorsal anterior cingulate cortex (BA 24. Interestingly, these differences in the SCH group were accompanied behaviorally by a protraction of time in both types of rating responses and by indicating funny punchlines less comprehensible. Summarizing, our results indicate neural substrates of humor comprehension

  17. Neural circuit of verbal humor comprehension in schizophrenia - an fMRI study.

    Science.gov (United States)

    Adamczyk, Przemysław; Wyczesany, Miroslaw; Domagalik, Aleksandra; Daren, Artur; Cepuch, Kamil; Błądziński, Piotr; Cechnicki, Andrzej; Marek, Tadeusz

    2017-01-01

    Individuals with schizophrenia exhibit problems with understanding the figurative meaning of language. This study evaluates neural correlates of diminished humor comprehension observed in schizophrenia. The study included chronic schizophrenia (SCH) outpatients (n = 20), and sex, age and education level matched healthy controls (n = 20). The fMRI punchline based humor comprehension task consisted of 60 stories of which 20 had funny, 20 nonsensical and 20 neutral (not funny) punchlines. After the punchlines were presented, the participants were asked to indicate whether the story was comprehensible and how funny it was. Three contrasts were analyzed in both groups reflecting stages of humor processing: abstract vs neutral stories - incongruity detection; funny vs abstract - incongruity resolution and elaboration; and funny vs neutral - complete humor processing. Additionally, parametric modulation analysis was performed using both subjective ratings separately. Between-group comparisons revealed that the SCH subjects had attenuated activation in the right posterior superior temporal gyrus (BA 41) in case of irresolvable incongruity processing of nonsensical puns; in the left dorsomedial middle and superior frontal gyri (BA 8/9) in case of incongruity resolution and elaboration processing of funny puns; and in the interhemispheric dorsal anterior cingulate cortex (BA 24) in case of complete processing of funny puns. Additionally, during comprehensibility ratings the SCH group showed a suppressed activity in the left dorsomedial middle and superior frontal gyri (BA 8/9) and revealed weaker activation during funniness ratings in the left dorsal anterior cingulate cortex (BA 24). Interestingly, these differences in the SCH group were accompanied behaviorally by a protraction of time in both types of rating responses and by indicating funny punchlines less comprehensible. Summarizing, our results indicate neural substrates of humor comprehension processing

  18. Remediation of Childhood Math Anxiety and Associated Neural Circuits through Cognitive Tutoring

    Science.gov (United States)

    Iuculano, Teresa; Chen, Lang

    2015-01-01

    Math anxiety is a negative emotional reaction that is characterized by feelings of stress and anxiety in situations involving mathematical problem solving. High math-anxious individuals tend to avoid situations involving mathematics and are less likely to pursue science, technology, engineering, and math-related careers than those with low math anxiety. Math anxiety during childhood, in particular, has adverse long-term consequences for academic and professional success. Identifying cognitive interventions and brain mechanisms by which math anxiety can be ameliorated in children is therefore critical. Here we investigate whether an intensive 8 week one-to-one cognitive tutoring program designed to improve mathematical skills reduces childhood math anxiety, and we identify the neurobiological mechanisms by which math anxiety can be reduced in affected children. Forty-six children in grade 3, a critical early-onset period for math anxiety, participated in the cognitive tutoring program. High math-anxious children showed a significant reduction in math anxiety after tutoring. Remarkably, tutoring remediated aberrant functional responses and connectivity in emotion-related circuits anchored in the basolateral amygdala. Crucially, children with greater tutoring-induced decreases in amygdala reactivity had larger reductions in math anxiety. Our study demonstrates that sustained exposure to mathematical stimuli can reduce math anxiety and highlights the key role of the amygdala in this process. Our findings are consistent with models of exposure-based therapy for anxiety disorders and have the potential to inform the early treatment of a disability that, if left untreated in childhood, can lead to significant lifelong educational and socioeconomic consequences in affected individuals. SIGNIFICANCE STATEMENT Math anxiety during early childhood has adverse long-term consequences for academic and professional success. It is therefore important to identify ways to alleviate

  19. Remediation of Childhood Math Anxiety and Associated Neural Circuits through Cognitive Tutoring.

    Science.gov (United States)

    Supekar, Kaustubh; Iuculano, Teresa; Chen, Lang; Menon, Vinod

    2015-09-09

    Math anxiety is a negative emotional reaction that is characterized by feelings of stress and anxiety in situations involving mathematical problem solving. High math-anxious individuals tend to avoid situations involving mathematics and are less likely to pursue science, technology, engineering, and math-related careers than those with low math anxiety. Math anxiety during childhood, in particular, has adverse long-term consequences for academic and professional success. Identifying cognitive interventions and brain mechanisms by which math anxiety can be ameliorated in children is therefore critical. Here we investigate whether an intensive 8 week one-to-one cognitive tutoring program designed to improve mathematical skills reduces childhood math anxiety, and we identify the neurobiological mechanisms by which math anxiety can be reduced in affected children. Forty-six children in grade 3, a critical early-onset period for math anxiety, participated in the cognitive tutoring program. High math-anxious children showed a significant reduction in math anxiety after tutoring. Remarkably, tutoring remediated aberrant functional responses and connectivity in emotion-related circuits anchored in the basolateral amygdala. Crucially, children with greater tutoring-induced decreases in amygdala reactivity had larger reductions in math anxiety. Our study demonstrates that sustained exposure to mathematical stimuli can reduce math anxiety and highlights the key role of the amygdala in this process. Our findings are consistent with models of exposure-based therapy for anxiety disorders and have the potential to inform the early treatment of a disability that, if left untreated in childhood, can lead to significant lifelong educational and socioeconomic consequences in affected individuals. Significance statement: Math anxiety during early childhood has adverse long-term consequences for academic and professional success. It is therefore important to identify ways to alleviate

  20. Associating a product with a luxury brand label modulates neural reward processing and favors choices in materialistic individuals.

    Science.gov (United States)

    Audrin, Catherine; Ceravolo, Leonardo; Chanal, Julien; Brosch, Tobias; Sander, David

    2017-11-23

    The present study investigated the extent to which luxury vs. non-luxury brand labels (i.e., extrinsic cues) randomly assigned to items and preferences for these items impact choice, and how this impact may be moderated by materialistic tendencies (i.e., individual characteristics). The main objective was to investigate the neural correlates of abovementioned effects using functional magnetic resonance imaging. Behavioural results showed that the more materialistic people are, the more they choose and like items labelled with luxury brands. Neuroimaging results revealed the implication of a neural network including the dorsolateral and ventromedial prefrontal cortex and the orbitofrontal cortex that was modulated by the brand label and also by the participants' preference. Most importantly, items with randomly assigned luxurious brand labels were preferentially chosen by participants and triggered enhanced signal in the caudate nucleus. This effect increased linearly with materialistic tendencies. Our results highlight the impact of brand-item association, although random in our study, and materialism on preference, relying on subparts of the brain valuation system for the integration of extrinsic cues, preferences and individual characteristics.

  1. Feedback that confirms reward expectation triggers auditory cortex activity.

    Science.gov (United States)

    Weis, Tina; Brechmann, André; Puschmann, Sebastian; Thiel, Christiane M

    2013-10-01

    Associative learning studies have shown that the anticipation of reward and punishment shapes the representation of sensory stimuli, which is further modulated by dopamine. Less is known about whether and how reward delivery activates sensory cortices and the role of dopamine at that time point of learning. We used an appetitive instrumental learning task in which participants had to learn that a specific class of frequency-modulated tones predicted a monetary reward following fast and correct responses in a succeeding reaction time task. These fMRI data were previously analyzed regarding the effect of reward anticipation, but here we focused on neural activity to the reward outcome relative to the reward expectation and tested whether such activation in the reward reception phase is modulated by L-DOPA. We analyzed neural responses at the time point of reward outcome under three different conditions: 1) when a reward was expected and received, 2) when a reward was expected but not received, and 3) when a reward was not expected and not received. Neural activity in auditory cortex was enhanced during feedback delivery either when an expected reward was received or when the expectation of obtaining no reward was correct. This differential neural activity in auditory cortex was only seen in subjects who learned the reward association and not under dopaminergic modulation. Our data provide evidence that auditory cortices are active at the time point of reward outcome. However, responses are not dependent on the reward itself but on whether the outcome confirmed the subject's expectations.

  2. Impaired Feedback Processing for Symbolic Reward in Individuals with Internet Game Overuse

    Directory of Open Access Journals (Sweden)

    Jinhee Kim

    2017-10-01

    Full Text Available Reward processing, which plays a critical role in adaptive behavior, is impaired in addiction disorders, which are accompanied by functional abnormalities in brain reward circuits. Internet gaming disorder, like substance addiction, is thought to be associated with impaired reward processing, but little is known about how it affects learning, especially when feedback is conveyed by less-salient motivational events. Here, using both monetary (±500 KRW and symbolic (Chinese characters “right” or “wrong” rewards and penalties, we investigated whether behavioral performance and feedback-related neural responses are altered in Internet game overuse (IGO group. Using functional MRI, brain responses for these two types of reward/penalty feedback were compared between young males with problems of IGO (IGOs, n = 18, mean age = 22.2 ± 2.0 years and age-matched control subjects (Controls, n = 20, mean age = 21.2 ± 2.1 during a visuomotor association task where associations were learned between English letters and one of four responses. No group difference was found in adjustment of error responses following the penalty or in brain responses to penalty, for either monetary or symbolic penalties. The IGO individuals, however, were more likely to fail to choose the response previously reinforced by symbolic (but not monetary reward. A whole brain two-way ANOVA analysis for reward revealed reduced activations in the IGO group in the rostral anterior cingulate cortex/ventromedial prefrontal cortex (vmPFC in response to both reward types, suggesting impaired reward processing. However, the responses to reward in the inferior parietal region and medial orbitofrontal cortex/vmPFC were affected by the types of reward in the IGO group. Unlike the control group, in the IGO group the reward response was reduced only for symbolic reward, suggesting lower attentional and value processing specific to symbolic reward. Furthermore

  3. Impaired Feedback Processing for Symbolic Reward in Individuals with Internet Game Overuse.

    Science.gov (United States)

    Kim, Jinhee; Kim, Hackjin; Kang, Eunjoo

    2017-01-01

    Reward processing, which plays a critical role in adaptive behavior, is impaired in addiction disorders, which are accompanied by functional abnormalities in brain reward circuits. Internet gaming disorder, like substance addiction, is thought to be associated with impaired reward processing, but little is known about how it affects learning, especially when feedback is conveyed by less-salient motivational events. Here, using both monetary (±500 KRW) and symbolic (Chinese characters "right" or "wrong") rewards and penalties, we investigated whether behavioral performance and feedback-related neural responses are altered in Internet game overuse (IGO) group. Using functional MRI, brain responses for these two types of reward/penalty feedback were compared between young males with problems of IGO (IGOs, n  = 18, mean age = 22.2 ± 2.0 years) and age-matched control subjects (Controls, n  = 20, mean age = 21.2 ± 2.1) during a visuomotor association task where associations were learned between English letters and one of four responses. No group difference was found in adjustment of error responses following the penalty or in brain responses to penalty, for either monetary or symbolic penalties. The IGO individuals, however, were more likely to fail to choose the response previously reinforced by symbolic (but not monetary) reward. A whole brain two-way ANOVA analysis for reward revealed reduced activations in the IGO group in the rostral anterior cingulate cortex/ventromedial prefrontal cortex (vmPFC) in response to both reward types, suggesting impaired reward processing. However, the responses to reward in the inferior parietal region and medial orbitofrontal cortex/vmPFC were affected by the types of reward in the IGO group. Unlike the control group, in the IGO group the reward response was reduced only for symbolic reward, suggesting lower attentional and value processing specific to symbolic reward. Furthermore, the more severe the

  4. Stress-protective neural circuits: not all roads lead through the prefrontal cortex.

    Science.gov (United States)

    Christianson, John P; Greenwood, Benjamin N

    2014-01-01

    Exposure to an uncontrollable stressor elicits a constellation of physiological and behavioral sequel in laboratory rats that often reflect aspects of anxiety and other emotional disruptions. We review evidence suggesting that plasticity within the serotonergic dorsal raphe nucleus (DRN) is critical to the expression of uncontrollable stressor-induced anxiety. Specifically, after uncontrollable stressor exposure subsequent anxiogenic stimuli evoke greater 5-HT release in DRN terminal regions including the amygdala and striatum; and pharmacological blockade of postsynaptic 5-HT(2C) receptors in these regions prevents expression of stressor-induced anxiety. Importantly, the controllability of stress, the presence of safety signals, and a history of exercise mitigate the expression of stressor-induced anxiety. These stress-protective factors appear to involve distinct neural substrates; with stressor controllability requiring the medial prefrontal cortex, safety signals the insular cortex and exercise affecting the 5-HT system directly. Knowledge of the distinct yet converging mechanisms underlying these stress-protective factors could provide insight into novel strategies for the treatment and prevention of stress-related psychiatric disorders.

  5. 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

  6. Defining biotypes for depression and anxiety based on large-scale circuit dysfunction: a theoretical review of the evidence and future directions for clinical translation.

    Science.gov (United States)

    Williams, Leanne M

    2017-01-01

    Complex emotional, cognitive and self-reflective functions rely on the activation and connectivity of large-scale neural circuits. These circuits offer a relevant scale of focus for conceptualizing a taxonomy for depression and anxiety based on specific profiles (or biotypes) of neural circuit dysfunction. Here, the theoretical review first outlines the current consensus as to what constitutes the organization of large-scale circuits in the human brain identified using parcellation and meta-analysis. The focus is on neural circuits implicated in resting reflection (default mode), detection of "salience," affective processing ("threat" and "reward"), "attention," and "cognitive control." Next, the current evidence regarding which type of dysfunctions in these circuits characterize depression and anxiety disorders is reviewed, with an emphasis on published meta-analyses and reviews of circuit dysfunctions that have been identified in at least two well-powered case:control studies. Grounded in the review of these topics, a conceptual framework is proposed for considering neural circuit-defined "biotypes." In this framework, biotypes are defined by profiles of extent of dysfunction on each large-scale circuit. The clinical implications of a biotype approach for guiding classification and treatment of depression and anxiety is considered. Future research directions will develop the validity and clinical utility of a neural circuit biotype model that spans diagnostic categories and helps to translate neuroscience into clinical practice in the real world. © 2016 Wiley Periodicals, Inc.

  7. With a little help from my friends: androgens tap BDNF signaling pathways to alter neural circuits.

    Science.gov (United States)

    Ottem, E N; Bailey, D J; Jordan, C L; Breedlove, S M

    2013-06-03

    Gonadal androgens are critical for the development and maintenance of sexually dimorphic regions of the male nervous system, which is critical for male-specific behavior and physiological functioning. In rodents, the motoneurons of the spinal nucleus of the bulbocavernosus (SNB) provide a useful example of a neural system dependent on androgen. Unless rescued by perinatal androgens, the SNB motoneurons will undergo apoptotic cell death. In adulthood, SNB motoneurons remain dependent on androgen, as castration leads to somal atrophy and dendritic retraction. In a second vertebrate model, the zebra finch, androgens are critical for the development of several brain nuclei involved in song production in males. Androgen deprivation during a critical period during postnatal development disrupts song acquisition and dimorphic size-associated nuclei. Mechanisms by which androgens exert masculinizing effects in each model system remain elusive. Recent studies suggest that brain-derived neurotrophic factor (BDNF) may play a role in androgen-dependent masculinization and maintenance of both SNB motoneurons and song nuclei of birds. This review aims to summarize studies demonstrating that BDNF signaling via its tyrosine receptor kinase (TrkB) receptor may work cooperatively with androgens to maintain somal and dendritic morphology of SNB motoneurons. We further describe studies that suggest the cellular origin of BDNF is of particular importance in androgen-dependent regulation of SNB motoneurons. We review evidence that androgens and BDNF may synergistically influence song development and plasticity in bird species. Finally, we provide hypothetical models of mechanisms that may underlie androgen- and BDNF-dependent signaling pathways. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Nitric oxide in the flocculus works the inhibitory neural circuits after unilateral labyrinthectomy.

    Science.gov (United States)

    Kitahara, T; Takeda, N; Kubo, T; Kiyama, H

    1999-01-09

    We previously reported that nitric oxide (NO) production in the unipolar brush (UB) cells is involved in vestibular compensation [T. Kitahara, N. Takeda, P.C. Emson, T. Kubo, H. Kiyama, Changes in nitric oxide synthase-like immunoreactivities in unipolar brush cells in the rat cerebellar flocculus after unilateral labyrinthectomy, Brain Res. 765 (1997) 1-6]. To further elucidate the role of NO-mediated signaling in flocculus after unilateral labyrinthectomy (UL), we examined UL-induced Fos expression, a marker of neural activity, in vestibular brainstem with continuous floccular infusions of Nomega-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase (NOS). After UL with floccular l-NAME infusions, Fos expression appeared in bilateral medial vestibular (MVe) and prepositus hypoglossal (PrH) nuclei. After UL with floccular saline infusions, however, Fos expression was observed only in the ipsi-MVe and contra-PrH. Furthermore, it has been revealed that UL with l-NAME infusions caused more severe vestibulo-ocular disturbances than UL with saline infusions at the initial stage [Kitahara et al. Brain Res. 765 (1997) 1-6]. Therefore, it is suggested that UL with floccular l-NAME infusions activates the contra-MVe and ipsi-PrH neurons and causes more severe imbalance between intervestibular nuclear activities at the initial stage. NO-mediated signaling in flocculus could be a possible driving force of the flocculus-mediated inhibition on the contra-MVe and ipsi-PrH at the initial stage of vestibular compensation. Copyright 1999 Elsevier Science B.V.

  9. Enabling functional neural circuit simulations with distributed computing of neuromodulated plasticity

    Directory of Open Access Journals (Sweden)

    Wiebke ePotjans

    2010-11-01

    Full Text Available A major puzzle in the field of computational neuroscience is how to relate system-level learning in higher organisms to synaptic plasticity. Recently, plasticity rules depending not only on pre- and post-synaptic activity but also on a third, non-local neuromodulatory signal have emerged as key candidates to bridge the gap between the macroscopic and the microscopic level of learning. Crucial insights into this topic are expected to be gained from simulations of neural systems, as these allow the simultaneous study of the multiple spatial and temporal scales that are involved in the problem. In particular, synaptic plasticity can be studied during the whole learning process, i.e. on a time scale of minutes to hours and across multiple brain areas. Implementing neuromodulated plasticity in large-scale network simulations where the neuromodulatory signal is dynamically generated by the network itself is challenging, because the network structure is commonly defined purely by the connectivity graph without explicit reference to the embedding of the nodes in physical space. Furthermore, the simulation of networks with realistic connectivity entails the use of distributed computing. A neuromodulated synapse must therefore be informed in an efficient way about the neuromodulatory signal, which is typically generated by a population of neurons located on different machines than either the pre- or post-synaptic neuron. Here, we develop a general framework to solve the problem of implementing neuromodulated plasticity in a time-driven distributed simulation, without reference to a particular implementation language, neuromodulator or neuromodulated plasticity mechanism. We implement our framework in the simulator NEST and demonstrate excellent scaling up to 1024 processors for simulations of a recurrent network incorporating neuromodulated spike-timing dependent plasticity.

  10. Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation.

    Directory of Open Access Journals (Sweden)

    David Zada

    2014-09-01

    Full Text Available The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2 gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8-/- zebrafish using zinc-finger nuclease (ZFN-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8-/- larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8-/- larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8-/- larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8-/- larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit

  11. Differential Effect of Reward and Punishment on Procedural Learning

    OpenAIRE

    Wächter, Tobias; Lungu, Ovidiu V.; Liu, Tao; Willingham, Daniel T.; Ashe, James

    2009-01-01

    Reward and punishment are potent modulators of associative learning in instrumental and classical conditioning. However, the effect of reward and punishment on procedural learning is not known. The striatum is known to be an important locus of reward-related neural signals and part of the neural substrate of procedural learning. Here, using an implicit motor learning task, we show that reward leads to enhancement of learning in human subjects, whereas punishment is associated only with improv...

  12. Serotonergic modulation of reward and punishment

    DEFF Research Database (Denmark)

    Macoveanu, Julian

    2014-01-01

    of evidence on the key role serotonin plays in reward processing. The reviewed research has revealed how central serotonin availability and receptor specific transmission modulates the neural response to both appetitive (rewarding) and aversive (punishing) stimuli in putative reward-related brain regions....... Thus, serotonin is suggested to be involved in behavioral control when there is a prospect of reward or punishment. The new findings may have implications in understanding psychiatric disorders such as major depression which is characterized by abnormal serotonergic function and reward...

  13. Individuals family history positive for alcoholism show functional magnetic resonance imaging differences in reward sensitivity that are related to impulsivity factors.

    Science.gov (United States)

    Andrews, Melissa M; Meda, Shashwath A; Thomas, Andre D; Potenza, Marc N; Krystal, John H; Worhunsky, Patrick; Stevens, Michael C; O'Malley, Stephanie; Book, Gregory A; Reynolds, Brady; Pearlson, Godfrey D

    2011-04-01

    Substance-abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay task. However, there is limited information on whether this uncharacteristic behavior represents a biological predisposition toward alcohol abuse, a consequence of chronic alcohol use, or both. We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a monetary incentive delay task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. During reward anticipation, functional magnetic resonance imaging data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism family history positive individuals in multiple regards. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Where is the comfort in comfort foods? Mechanisms linking fat signaling, reward, and emotion.

    Science.gov (United States)

    Weltens, N; Zhao, D; Van Oudenhove, L

    2014-03-01

    Food in general, and fatty foods in particular, have obtained intrinsic reward value throughout evolution. This reward value results from an interaction between exteroceptive signals from different sensory modalities, interoceptive hunger/satiety signals from the gastrointestinal tract to the brain, as well as ongoing affective and cognitive processes. Further evidence linking food to emotions stems from folk psychology ('comfort foods') and epidemiological studies demonstrating high comorbidity rates between disorders of food intake, including obesity, and mood disorders such as depression. This review paper aims to give an overview of current knowledge on the neurophysiological mechanisms underlying the link between (fatty) foods, their reward value, and emotional responses to (anticipation of) their intake in humans. Firstly, the influence of exteroceptive sensory signals, including visual, olfactory ('anticipatory food reward'), and gustatory ('consummatory food reward'), on the encoding of reward value in the (ventral) striatum and of subjective pleasantness in the cingulate and orbitofrontal cortex will be discussed. Differences in these pathways and mechanisms between lean and obese subjects will be highlighted. Secondly, recent studies elucidating the mechanisms of purely interoceptive fatty acid-induced signaling from the gastrointestinal tract to the brain, including the role of gut peptides, will be presented. These studies have demonstrated that such subliminal interoceptive stimuli may impact on hedonic circuits in the brain, and thereby influence the subjective and neural responses to negative emotion induction. This suggests that the effect of foods on mood may even occur independently from their exteroceptive sensory properties. © 2014 John Wiley & Sons Ltd.

  15. Neuroendocrine circuits governing energy balance and stress regulation: functional overlap and therapeutic implications.

    Science.gov (United States)

    Ulrich-Lai, Yvonne M; Ryan, Karen K

    2014-06-03

    Significant comorbidities between obesity-related metabolic disease and stress-related psychological disorders suggest important functional interactions between energy balance and brain stress integration. Largely overlapping neural circuits control these systems, and this anatomical arrangement optimizes opportunities for mutual influence. Here we first review the current literature identifying effects of metabolic neuroendocrine signals on stress regulation, and vice versa. Next, the contributions of reward-driven food intake to these metabolic and stress interactions are discussed. Lastly, we consider the interrelationships between metabolism, stress, and reward in light of their important implications in the development of therapies for metabolism- or stress-related disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. KB220Z™ a Pro-Dopamine Regulator Associated with the Protracted, Alleviation of Terrifying Lucid Dreams. Can We Infer Neuroplasticity-induced Changes in the Reward Circuit?

    Science.gov (United States)

    McLaughlin, Thomas; Febo, Marcelo; Badgaiyan, Rajendra D; Barh, Debmalya; Dushaj, Kristina; Braverman, Eric R; Li, Mona; Madigan, Margaret A; Blum, Kenneth

    2016-01-01

    Recent reports by our laboratory have indicated that lucid dreams may be linked to psychiatric conditions, including Attention Deficit Hyperactivity Disorder (ADHD) and other Reward Deficiency Syndrome-related diagnoses. In the latter case, it has been our observation that such lucid dreams can be unpleasant and frequently terrifying. We present four cases of a dramatic and persistent alleviation of terrifying, lucid dreams in patients diagnosed with ADHD/PTSD and/or opiate/opioid addiction. The amelioration of such dreams could well be permanent, since the patients had stopped taking the nutraceutical for between 10 to 12 months, without their recollection or recurrence. In the first case, the patient is a 47-year-old, married male who required continued Buprenorphine/ Naloxone (Suboxone) treatment. The second case involved a 32-year-old female with the sole diagnosis of ADHD. The third case involves a 38-year-old male who carried the diagnoses of Substance Use Dependence and ADHD. The fourth case involved a 50-year-old female with the diagnoses of Alcohol Abuse, ADHD and Posttraumatic Stress Disorder. In order to attempt to understand the possibility of neuroplasticity, we evaluated the effect of KB220Z in non-opioid-addicted rats utilizing functional Magnetic Resonance Imaging methodology. While we cannot make a definitive claim because rat brain functional connectivity may not be exactly the same as humans, it does provide some interesting clues. We did find following seeding of the dorsal hippocampus, enhanced connectivity volume across several Regions of Interest (ROI), with the exception of the pre- frontal cortex. Interestingly, the latter region is only infrequently activated in lucid human dreaming, when the dreamer reports that he/she had the thought that they were dreaming during the lucid dream. The four patients initially reported a gradual but, then, complete amelioration of their long-term, terrifying, lucid dreams, while taking KB220Z. The

  17. KB220Z™ a Pro-Dopamine Regulator Associated with the Protracted, Alleviation of Terrifying Lucid Dreams. Can We Infer Neuroplasticity-induced Changes in the Reward Circuit?

    Science.gov (United States)

    McLaughlin, Thomas; Febo, Marcelo; Badgaiyan, Rajendra D.; Barh, Debmalya; Dushaj, Kristina; Braverman, Eric R.; Li, Mona; Madigan, Margaret A.; Blum, Kenneth

    2017-01-01

    Background Recent reports by our laboratory have indicated that lucid dreams may be linked to psychiatric conditions, including Attention Deficit Hyperactivity Disorder (ADHD) and other Reward Deficiency Syndrome-related diagnoses. In the latter case, it has been our observation that such lucid dreams can be unpleasant and frequently terrifying. Case presentations We present four cases of a dramatic and persistent alleviation of terrifying, lucid dreams in patients diagnosed with ADHD/PTSD and/or opiate/opioid addiction. The amelioration of such dreams could well be permanent, since the patients had stopped taking the nutraceutical for between 10 to 12 months, without their recollection or recurrence. In the first case, the patient is a 47-year-old, married male who required continued Buprenorphine/ Naloxone (Suboxone) treatment. The second case involved a 32-year-old female with the sole diagnosis of ADHD. The third case involves a 38-year-old male who carried the diagnoses of Substance Use Dependence and ADHD. The fourth case involved a 50-year-old female with the diagnoses of Alcohol Abuse, ADHD and Posttraumatic Stress Disorder. Results In order to attempt to understand the possibility of neuroplasticity, we evaluated the effect of KB220Z in non-opioid-addicted rats utilizing functional Magnetic Resonance Imaging methodology. While we cannot make a definitive claim because rat brain functional connectivity may not be exactly the same as humans, it does provide some interesting clues. We did find following seeding of the dorsal hippocampus, enhanced connectivity volume across several Regions of Interest (ROI), with the exception of the pre- frontal cortex. Interestingly, the latter region is only infrequently activated in lucid human dreaming, when the dreamer reports that he/she had the thought that they were dreaming during the lucid dream. Conclusions The four patients initially reported a gradual but, then, complete amelioration of their long

  18. The rewarding nature of social interactions

    Directory of Open Access Journals (Sweden)

    Sören Krach

    2010-05-01

    Full Text Available The objective of this short review is to highlight rewarding aspects of social interactions for humans and discuss their neural basis. Thereby we report recent research findings to illustrate how social stimuli in general are processed in the reward system and highlight the role of Theory of Mind (ToM as one mediating process for experiencing social reward during social interactions. In conclusion we discuss clinical implications for psychiatry and psychotherapy.

  19. Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

    Science.gov (United States)

    Smoski, Moria J; Rittenberg, Alison; Dichter, Gabriel S

    2011-12-30

    Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Osmotic release oral system-methylphenidate improves neural activity during low reward processing in children and adolescents with attention-deficit/hyperactivity disorder☆

    Science.gov (United States)

    Mizuno, Kei; Yoneda, Tetsuya; Komi, Masanori; Hirai, Toshinori; Watanabe, Yasuyoshi; Tomoda, Akemi

    2013-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) studies revealed that acute treatment with MPH alters activation of the nucleus accumbens during delay aversion in children and adolescents with ADHD, the effects a relatively long period of OROS-MPH treatment on delay aversion as well as reward sensitivity remain unclear. Thus, we evaluated brain activation with fMRI during a reward sensitivity paradigm that consists of high monetary reward and low monetary reward conditions before and after a 3-month treatment with OROS-MPH in 17 children and adolescents with ADHD (mean age, 13.3 ± 2.2) and 17 age- and sex-matched healthy controls (mean age, 13.0 ± 1.9). We found that before treatment there was decreased activation of the nucleus accumbens and thalamus in patients with ADHD during only the low monetary reward condition, which was improved to same level as those of the healthy controls after the treatment. The observed change in brain activity was associated with improved ADHD symptom scores, which were derived from Japanese versions of the ADHD rating scale-IV. These results suggest that treatment with OROS-MPH for a relatively long period is effective in controlling reward sensitivity in children and adolescents with ADHD. PMID:24179790

  1. Osmotic release oral system-methylphenidate improves neural activity during low reward processing in children and adolescents with attention-deficit/hyperactivity disorder ?

    OpenAIRE

    Mizuno, Kei; Yoneda, Tetsuya; Komi, Masanori; Hirai, Toshinori; Watanabe, Yasuyoshi; Tomoda, Akemi

    2013-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) stud...

  2. Osmotic release oral system-methylphenidate improves neural activity during low reward processing in children and adolescents with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Mizuno, Kei; Yoneda, Tetsuya; Komi, Masanori; Hirai, Toshinori; Watanabe, Yasuyoshi; Tomoda, Akemi

    2013-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is neurobehavioral disorder characterized by inattention, hyperactivity/impulsivity and impaired reward system function, such as delay aversion and low reward sensitivity. The pharmacological treatment for ADHD includes methylphenidate (MPH), or osmotic release oral system-MPH (OROS-MPH), which increases extrasynaptic dopamine and noradrenaline levels by blocking their reuptake. Although previous functional magnetic resonance imaging (fMRI) studies revealed that acute treatment with MPH alters activation of the nucleus accumbens during delay aversion in children and adolescents with ADHD, the effects a relatively long period of OROS-MPH treatment on delay aversion as well as reward sensitivity remain unclear. Thus, we evaluated brain activation with fMRI during a reward sensitivity paradigm that consists of high monetary reward and low monetary reward conditions before and after a 3-month treatment with OROS-MPH in 17 children and adolescents with ADHD (mean age, 13.3 ± 2.2) and 17 age- and sex-matched healthy controls (mean age, 13.0 ± 1.9). We found that before treatment there was decreased activation of the nucleus accumbens and thalamus in patients with ADHD during only the low monetary reward condition, which was improved to same level as those of the healthy controls after the treatment. The observed change in brain activity was associated with improved ADHD symptom scores, which were derived from Japanese versions of the ADHD rating scale-IV. These results suggest that treatment with OROS-MPH for a relatively long period is effective in controlling reward sensitivity in children and adolescents with ADHD.

  3. Dyadic social interaction as an alternative reward to cocaine

    Directory of Open Access Journals (Sweden)

    Gerald eZernig

    2013-09-01

    Full Text Available Individuals suffering from substance use disorders often show severely impaired social interaction, preferring drugs of abuse to the contact with others. Their impaired social interaction is doubly harmful for them as (1 therapy itself is based and dependent on social interaction and as (2 social interaction is not available to them as an "alternative", i.e., non-drug reward, decreasing their motivation to stop drug use. We therefore developed an animal experimental model to investigate the neurobiology of dyadic social interaction- vs cocaine reward. We took care to avoid (a engaging sexual attraction-related aspects of such a social interaction and (b hierarchical difference as confounding stimuli. The cocaine- or social interaction stimulus was offered - in a mutually exclusive setting - within the confines of a conditioned place preference (CPP apparatus. In our paradigm, only four 15-min episodes of social interaction proved sufficient to (i switch the rats' preference from cocaine-associated contextual stimuli to social interaction CPP and (ii inhibit the subsequent reacquisition/reexpression of cocaine CPP. The behavioral effect was paralleled by a reversal of brain activation (i.e., EGR1 expression in the nucleus accumbens, the central and basolateral amygdala, and the ventral tegmental area. Of relevance for the psychotherapy of addictive disorders, the most rewarding sensory component of the composite stimulus 'social interaction' was touch. To test our hypothesis that motivation is encoded in neuron ensembles dedicated to specific reward scenarios, we are currently (1 mapping the neural circuits involved in cocaine- vs social interaction reward and (2 adapting our paradigm for C57BL/6 mice to make use of the plethora of transgenic models available in this species.

  4. Dyadic social interaction as an alternative reward to cocaine.

    Science.gov (United States)

    Zernig, Gerald; Kummer, Kai K; Prast, Janine M

    2013-09-12

    Individuals suffering from substance use disorders often show severely impaired social interaction, preferring drugs of abuse to the contact with others. Their impaired social interaction is doubly harmful for them as (1) therapy itself is based and dependent on social interaction and as (2) social interaction is not available to them as an "alternative", i.e., non-drug reward, decreasing their motivation to stop drug use. We therefore developed an animal experimental model to investigate the neurobiology of dyadic social interaction- vs. cocaine reward. We took care to avoid: (a) engaging sexual attraction-related aspects of such a social interaction and (b) hierarchical difference as confounding stimuli. The cocaine- or social interaction stimulus was offered - in a mutually exclusive setting - within the confines of a conditioned place preference (CPP) apparatus. In our paradigm, only four 15-min episodes of social interaction proved sufficient to (i) switch the rats' preference from cocaine-associated contextual stimuli to social interaction CPP and (ii) inhibit the subsequent reacquisition/reexpression of cocaine CPP. This behavioral effect was paralleled by a reversal of brain activation (i.e., EGR1 expression) in the nucleus accumbens, the central and basolateral amygdala, and the ventral tegmental area. Of relevance for the psychotherapy of addictive disorders, the most rewarding sensory component of the composite stimulus "social interaction" was touch. To test our hypothesis that motivation is encoded in neuron ensembles dedicated to specific reward scenarios, we are currently (1) mapping the neural circuits involved in cocaine- vs. social-interaction reward and (2) adapting our paradigm for C57BL/6 mice to make use of the plethora of transgenic models available in this species.

  5. The Use of Modular, Electronic Neuron Simulators for Neural Circuit Construction Produces Learning Gains in an Undergraduate Anatomy and Physiology Course.

    Science.gov (United States)

    Petto, Andrew; Fredin, Zachary; Burdo, Joseph

    2017-01-01

    During the spring of 2016 at the University of Wisconsin-Milwaukee, we implemented a novel educational technology designed to teach undergraduates about the nervous system while allowing them to physically construct their own neural circuits. Modular, electronic neuron simulators called NeuroBytes were used by the students in BIOSCI202 Anatomy and Physiology I, a four-credit course consisting of three hours per week each of lecture and laboratory time. 162 students participated in the laboratory sessions that covered reflexes; 83 in the experimental sections used the NeuroBytes to build a model of the patellar tendon reflex, while 79 in the control sections participated in alternate reflex curricula. To address the question of whether or not the NeuroBytes-based patellar tendon reflex simulation brought about learning gains, the control and experimental group students underwent pre/post testing before and after their laboratory sections. We found that for several of the neuroscience and physiology concepts assessed on the test, the experimental group students had significantly greater declarative learning gains between the pre- and post-test as compared to the control group students. While there are numerous virtual neuroscience education tools available to undergraduate educators, there are relatively few designed to engage students in the basics of electrophysiology and neural circuitry using physical manipulatives, and none to our knowledge that allow them to build circuits from functioning hand-held "neurons."

  6. Multi-array silicon probes with integrated optical fibers: light-assisted perturbation and recording of local neural circuits in the behaving animal.

    Science.gov (United States)

    Royer, Sébastien; Zemelman, Boris V; Barbic, Mladen; Losonczy, Attila; Buzsáki, György; Magee, Jeffrey C

    2010-06-01

    Recordings of large neuronal ensembles and neural stimulation of high spatial and temporal precision are important requisites for studying the real-time dynamics of neural networks. Multiple-shank silicon probes enable large-scale monitoring of individual neurons. Optical stimulation of genetically targeted neurons expressing light-sensitive channels or other fast (milliseconds) actuators offers the means for controlled perturbation of local circuits. Here we describe a method to equip the shanks of silicon probes with micron-scale light guides for allowing the simultaneous use of the two approaches. We then show illustrative examples of how these compact hybrid electrodes can be used in probing local circuits in behaving rats and mice. A key advantage of these devices is the enhanced spatial precision of stimulation that is achieved by delivering light close to the recording sites of the probe. When paired with the expression of light-sensitive actuators within genetically specified neuronal populations, these devices allow the relatively straightforward and interpretable manipulation of network activity.

  7. Response perseveration and ventral prefrontal sensitivity to reward and punishment in male problem gamblers and smokers.

    Science.gov (United States)

    de Ruiter, Michiel B; Veltman, Dick J; Goudriaan, Anna E; Oosterlaan, Jaap; Sjoerds, Zsuzsika; van den Brink, Wim

    2009-03-01

    Pathological gambling (PG) is associated with maladaptive perseverative behavior, but the underlying mechanism and neural circuitry is not completely clear. Here, the hypothesis was tested that PG is characterized by response perseveration and abnormalities in reward and/or punishment sensitivity in the ventral frontostriatal circuit. Executive functioning was assessed to verify if these effects are independent of the dorsal frontostriatal circuit. A group of smokers was also included to examine whether impairments in PG generalize to substance use disorders. Response perseveration and reward/punishment sensitivity were measured with a probabilistic reversal-learning task, in which subjects could win and lose money. Executive functioning was measured with a planning task, the Tower of London. Performance and fMRI data were acquired in 19 problem gamblers, 19 smokers, and 19 healthy controls. Problem gamblers showed severe response perseveration, associated with reduced activation of right ventrolateral prefrontal cortex in response to both monetary gain and loss. Results did not fully generalize to smokers. Planning performance and related activation of the dorsal frontostriatal circuit were intact in both problem gamblers and smokers. PG is related to response perseveration and diminished reward and punishment sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex when money is gained and lost. Moreover, intact planning abilities and normal dorsal frontostriatal responsiveness indicate that this deficit is not due to impaired executive functioning. Response perseveration and ventral prefrontal hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen in chemical and nonchemical addictions.

  8. Learning Reward Uncertainty in the Basal Ganglia.

    Directory of Open Access Journals (Sweden)

    John G Mikhael

    2016-09-01

    Full Text Available Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid options with variable reward can be controlled by increasing (or decreasing the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions.

  9. Differential effect of reward and punishment on procedural learning.

    Science.gov (United States)

    Wächter, Tobias; Lungu, Ovidiu V; Liu, Tao; Willingham, Daniel T; Ashe, James

    2009-01-14

    Reward and punishment are potent modulators of associative learning in instrumental and classical conditioning. However, the effect of reward and punishment on procedural learning is not known. The striatum is known to be an important locus of reward-related neural signals and part of the neural substrate of procedural learning. Here, using an implicit motor learning task, we show that reward leads to enhancement of learning in human subjects, whereas punishment is associated only with improvement in motor performance. Furthermore, these behavioral effects have distinct neural substrates with the learning effect of reward being mediated through the dorsal striatum and the performance effect of punishment through the insula. Our results suggest that reward and punishment engage separate motivational systems with distinctive behavioral effects and neural substrates.

  10. Reward and motivation in pain and pain relief.

    Science.gov (United States)

    Navratilova, Edita; Porreca, Frank

    2014-10-01

    Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain.

  11. A neural circuit transforming temporal periodicity information into a rate-based representation in the mammalian auditory system

    DEFF Research Database (Denmark)

    Dicke, Ulrike; Ewert, Stephan D.; Dau, Torsten

    2007-01-01

    to previous modeling studies, the present circuit does not employ a continuously changing temporal parameter to obtain different best modulation frequencies BMFs of the IC bandpass units. Instead, different BMFs are yielded from varying the number of input units projecting onto different bandpass units...

  12. Introduction: Addiction and Brain Reward and Anti-Reward Pathways

    Science.gov (United States)

    Gardner, Eliot L.

    2013-01-01

    Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly) and that they enhance the functioning of the reward circuitry of the brain (producing the “high” that the drug-user seeks). The core reward circuitry consists of an “in series” circuit linking the ventral tegmental area, nucleus accumbens, and ventral pallidum - via the medial forebrain bundle. Although originally believed to encode simply the set-point of hedonic tone, these circuits are now believed to be functionally far more complex - also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. “Hedonic dysregulation” within these circuits may lead to addiction. The “second-stage” dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component. All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dopaminergic reward synaptic function in the nucleus accumbens. Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level). For some classes of addictive drugs (e.g., opiates), tolerance to the euphoric effects develops with chronic use. Post-use dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get “high,” but simply to get back to normal (“get straight”). The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically, and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse. There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction. In short, the

  13. A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila.

    Science.gov (United States)

    Beshel, Jennifer; Dubnau, Josh; Zhong, Yi

    2017-01-10

    Leptin, a typically adipose-derived "satiety hormone," has a well-established role in weight regulation. Here we describe a functionally conserved model of genetically induced obesity in Drosophila by manipulating the fly leptin analog unpaired 1 (upd1). Unexpectedly, cell-type-specific knockdown reveals upd1 in the brain, not the adipose tissue, mediates obesity-related traits. Disrupting brain-derived upd1 in flies leads to all the hallmarks of mammalian obesity: increased attraction to food cues, increased food intake, and increased weight. These effects are mediated by domeless receptors on neurons expressing Drosophila neuropeptide F, the orexigenic mammalian neuropeptide Y homolog. In vivo two-photon imaging reveals upd1 and domeless inhibit this hedonic signal in fed animals. Manipulations along this central circuit also create hypersensitivity to obesogenic conditions, emphasizing the critical interplay between biological predisposition and environment in overweight and obesity prevalence. We propose adipose- and brain-derived upd/leptin may control differing features of weight regulation through distinct neural circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Sites of Plasticity in the Neural Circuit Mediating Tentacle Withdrawal in the Snail Helix aspersa: Implications for Behavioral Change and Learning Kinetics

    Science.gov (United States)

    Prescott, Steven A.; Chase, Ronald

    1999-01-01

    The tentacle withdrawal reflex of the snail Helix aspersa exhibits a complex combination of habituation and sensitization consistent with the dual-process theory of plasticity. Habituation, sensitization, or a combination of both were elicited by varying stimulation parameters and lesion condition. Analysis of response plasticity shows that the late phase of the response is selectively enhanced by sensitization, whereas all phases are decreased by habituation. Previous data have shown that tentacle withdrawal is mediated conjointly by parallel monosynaptic and polysynaptic pathways. The former mediates the early phase, whereas the latter mediates the late phase of the response. Plastic loci were identified by stimulating and recording at different points within the neural circuit, in combination with selective lesions. Results indicate that depression occurs at an upstream locus, before circuit divergence, and is therefore expressed in all pathways, whereas facilitation requires downstream facilitatory neurons and is selectively expressed in polysynaptic pathways. Differential expression of plasticity between pathways helps explain the behavioral manifestation of depression and facilitation. A simple mathematical model is used to show how serial positioning of depression and facilitation can explain the kinetics of dual-process learning. These results illustrate how the position of cellular plasticity in the network affects behavioral change and how forms of plasticity can interact to determine the kinetics of the net changes. PMID:10509707

  15. 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.

  16. Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats.

    Science.gov (United States)

    Choi, Ga-Young; Kim, Hyun-Bum; Hwang, Eun-Sang; Lee, Seok; Kim, Min-Ji; Choi, Ji-Young; Lee, Sung-Ok; Kim, Sang-Seong; Park, Ji-Ho

    2017-01-01

    Curcumin is a major diarylheptanoid component of Curcuma longa with traditional usage for anxiety and depression. It has been known for the anti-inflammatory, antistress, and neurotropic effects. Here we examined curcumin effect in neural plasticity and cell viability. 60-channel multielectrode array was applied on organotypic hippocampal slice cultures (OHSCs) to monitor the effect of 10 μM curcumin in long-term depression (LTD) through low-frequency stimulation (LFS) to the Schaffer collaterals and commissural pathways. Cell viability was assayed by propidium iodide uptake test in OHSCs. In addition, the influence of oral curcumin administration on rat behavior was assessed with the forced swim test (FST). Finally, protein expression levels of brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2) were measured by Western blot in chronically stressed rats. Our results demonstrated that 10 μM curcumin attenuated LTD and reduced cell death. It also recovered the behavior immobility of FST, rescued the attenuated BDNF expression, and inhibited the enhancement of COX-2 expression in stressed animals. These findings indicate that curcumin can enhance postsynaptic electrical reactivity and cell viability in intact neural circuits with antidepressant-like effects, possibly through the upregulation of BDNF and reduction of inflammatory factors in the brain.

  17. Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats

    Directory of Open Access Journals (Sweden)

    Ga-Young Choi

    2017-01-01

    Full Text Available Curcumin is a major diarylheptanoid component of Curcuma longa with traditional usage for anxiety and depression. It has been known for the anti-inflammatory, antistress, and neurotropic effects. Here we examined curcumin effect in neural plasticity and cell viability. 60-channel multielectrode array was applied on organotypic hippocampal slice cultures (OHSCs to monitor the effect of 10 μM curcumin in long-term depression (LTD through low-frequency stimulation (LFS to the Schaffer collaterals and commissural pathways. Cell viability was assayed by propidium iodide uptake test in OHSCs. In addition, the influence of oral curcumin administration on rat behavior was assessed with the forced swim test (FST. Finally, protein expression levels of brain-derived neurotrophic factor (BDNF and cyclooxygenase-2 (COX-2 were measured by Western blot in chronically stressed rats. Our results demonstrated that 10 μM curcumin attenuated LTD and reduced cell death. It also recovered the behavior immobility of FST, rescued the attenuated BDNF expression, and inhibited the enhancement of COX-2 expression in stressed animals. These findings indicate that curcumin can enhance postsynaptic electrical reactivity and cell viability in intact neural circuits with antidepressant-like effects, possibly through the upregulation of BDNF and reduction of inflammatory factors in the brain.

  18. Motivation and reward systems

    NARCIS (Netherlands)

    van Eerde, W.; Vodosek, M.; den Hartog, D.N.; McNett, J.M.

    2014-01-01

    Reward systems are identified as one of the human resource management (HRM) practices that may impact motivation. Reward systems may consist of several components, including financial and nonfinancial rewards, in fixed and variable amounts. Reinforcement, expectancy, and equity principles are

  19. Diminished choice effect on anticipating improbable rewards.

    Science.gov (United States)

    Chen, Weiran; Li, Qi; Mei, Shuting; Yi, Wei; Yang, Guochun; Zhou, Shiyu; Liu, Xun; Zheng, Ya

    2018-02-01

    Previous research found that the neural substrates underlying perceived control highly overlap those of reward system, especially during reward anticipation stage. The current event-related potential study examined whether the experience of choice by which individuals exercise control is modulated by reward probability during reward anticipation stage as indexed by the stimulus-preceding negativity (SPN). Thirty participants performed a cued gambling task during which choices could be made either by themselves (a choice condition) or by a computer (a no-choice condition) with three levels of reward probability (low, medium, and high) while their EEG was recording. As expected, the participants perceived higher control during the choice compared to no-choice condition. Correspondingly, the SPN was enhanced in the choice condition than the no-choice condition. Critically, the SPN choice effect was present when reward probability was high and medium, but was diminished when reward probability was low. These findings suggest that the perceived control as exercised by choice is associated with reward anticipation, which may be sensitive to the fundamental properties of reward. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Willing to wait: Elevated reward-processing EEG activity associated with a greater preference for larger-but-delayed rewards.

    Science.gov (United States)

    Pornpattananangkul, Narun; Nusslock, Robin

    2016-10-01

    While almost everyone discounts the value of future rewards over immediate rewards, people differ in their so-called delay-discounting. One of the several factors that may explain individual differences in delay-discounting is reward-processing. To study individual-differences in reward-processing, however, one needs to consider the heterogeneity of neural-activity at each reward-processing stage. Here using EEG, we separated reward-related neural activity into distinct reward-anticipation and reward-outcome stages using time-frequency characteristics. Thirty-seven individuals first completed a behavioral delay-discounting task. Then reward-processing EEG activity was assessed using a separate reward-learning task, called a reward time-estimation task. During this EEG task, participants were instructed to estimate time duration and were provided performance feedback on a trial-by-trial basis. Participants received monetary-reward for accurate-performance on Reward trials, but not on No-Reward trials. Reward trials, relative to No-Reward trials, enhanced EEG activity during both reward-anticipation (including, cued-locked delta power during cue-evaluation and pre-feedback alpha suppression during feedback-anticipation) and reward-outcome (including, feedback-locked delta, theta and beta power) stages. Moreover, all of these EEG indices correlated with behavioral performance in the time-estimation task, suggesting their essential roles in learning and adjusting performance to maximize winnings in a reward-learning situation. Importantly, enhanced EEG power during Reward trials, as reflected by stronger 1) pre-feedback alpha suppression, 2) feedback-locked theta and 3) feedback-locked beta, was associated with a greater preference for larger-but-delayed rewards in a separate, behavioral delay-discounting task. Results highlight the association between a stronger preference toward larger-but-delayed rewards and enhanced reward-processing. Moreover, our reward

  1. Forgetting the best when predicting the worst: Preliminary observations on neural circuit function in adolescent social anxiety

    Directory of Open Access Journals (Sweden)

    Johanna M. Jarcho

    2015-06-01

    Full Text Available Social anxiety disorder typically begins in adolescence, a sensitive period for brain development, when increased complexity and salience of peer relationships requires novel forms of social learning. Disordered social learning in adolescence may explain how brain dysfunction promotes social anxiety. Socially anxious adolescents (n = 15 and adults (n = 19 and non-anxious adolescents (n = 24 and adults (n = 32 predicted, then received, social feedback from high and low-value peers while undergoing functional magnetic resonance imaging (fMRI. A surprise recall task assessed memory biases for feedback. Neural correlates of social evaluation prediction errors (PEs were assessed by comparing engagement to expected and unexpected positive and negative feedback. For socially anxious adolescents, but not adults or healthy participants of either age group, PEs elicited heightened striatal activity and negative fronto-striatal functional connectivity. This occurred selectively to unexpected positive feedback from high-value peers and corresponded with impaired memory for social feedback. While impaired memory also occurred in socially-anxious adults, this impairment was unrelated to brain-based PE activity. Thus, social anxiety in adolescence may relate to altered neural correlates of PEs that contribute to impaired learning about social feedback. Small samples necessitate replication. Nevertheless, results suggest that the relationship between learning and fronto-striatal function may attenuate as development progresses.

  2. An Update on the Role of Serotonin and its Interplay with Dopamine for Reward

    Directory of Open Access Journals (Sweden)

    Adrian G. Fischer

    2017-10-01

    Full Text Available The specific role of serotonin and its interplay with dopamine (DA in adaptive, reward guided behavior as well as drug dependance, still remains elusive. Recently, novel methods allowed cell type specific anatomical, functional and interventional analyses of serotonergic and dopaminergic circuits, promising significant advancement in understanding their functional roles. Furthermore, it is increasingly recognized that co-release of neurotransmitters is functionally relevant, understanding of which is required in order to interpret results of pharmacological studies and their relationship to neural recordings. Here, we review recent animal studies employing such techniques with the aim to connect their results to effects observed in human pharmacological studies and subjective effects of drugs. It appears that the additive effect of serotonin and DA conveys significant reward related information and is subjectively highly euphorizing. Neither DA nor serotonin alone have such an effect. This coincides with optogenetically targeted recordings in mice, where the dopaminergic system codes reward prediction errors (PE, and the serotonergic system mainly unsigned PE. Overall, this pattern of results indicates that joint activity between both systems carries essential reward information and invites parallel investigation of both neurotransmitter systems.

  3. Assessing fear following retrieval+extinction through suppression of baseline reward seeking vs. freezing

    Directory of Open Access Journals (Sweden)

    Jason eShumake

    2015-12-01

    Full Text Available Freezing has become the predominant measure used in rodent studies of conditioned fear, but conditioned suppression of reward-seeking behavior may provide a measure that is more relevant to human anxiety disorders; that is, a measure of how fear interferes with the enjoyment of pleasurable activities. Previous work has found that an isolated presentation of a fear conditioned stimulus prior to extinction training (retrieval + extinction results in a more robust and longer-lasting reduction in fear. The objective of this study was to assess whether the retrieval + extinction effect is evident using conditioned suppression of reward seeking, operationalized as a reduction in baseline licking (without prior water deprivation for a 10% sucrose solution. We found that, compared to freezing, conditioned suppression of reward seeking was much more sensitive to fear conditioning and far less responsive to extinction training. As in previous work, we found that retrieval + extinction reduced post-extinction fear reinstatement when measured as freezing, but it did not reduce fear reinstatement when measured as conditioned suppression. This suggests that there is still residual fear following retrieval + extinction, or that this procedure only modifies memory traces in neural circuits relevant to the expression of freezing, but not to the suppression of reward seeking.

  4. Ventral striatum response during reward and punishment reversal learning in unmedicated major depressive disorder.

    Science.gov (United States)

    Robinson, Oliver J; Cools, Roshan; Carlisi, Christina O; Sahakian, Barbara J; Drevets, Wayne C

    2012-02-01

    Affective biases may underlie many of the key symptoms of major depressive disorder, from anhedonia to altered cognitive performance. Understanding the cause of these biases is therefore critical in the quest for improved treatments. Depression is associated, for example, with a negative affective bias in reversal learning. However, despite the fact that reversal learning is associated with striatal response in healthy individuals and depressed individuals exhibit attenuated striatal function on multiple tasks, studies to date have not demonstrated striatal involvement in the negative bias in reversal learning in depression. In this study, the authors sought to determine whether this may be because reversal learning tasks conventionally used to study behavior examine reversals only on the basis of unexpected punishment and therefore do not adequately separate reward- and punishment-based behavior. The authors used functional MRI to compare the hemodynamic response to a reversal learning task with mixed reward- and punishment-based reversal stages between individuals with unmedicated major depressive disorder (N=13) and healthy comparison subjects (N=14). Impaired reward (but not punishment) reversal accuracy was found alongside attenuated anteroventral striatal response to unexpected reward in depression. Attenuated neurophysiological response of the anteroventral striatum may reflect dysfunction in circuits involving afferent projections from the orbitofrontal, limbic, and/or mesostriatal dopaminergic pathways, which conceivably may, together with the ventral striatum, underlie anhedonia in depression. Learning to appreciate and enjoy positive life experiences is critical for recovery from depression. This study pinpoints a neural target for such recovery.

  5. Dorsolateral prefrontal cortex modulates striatal reward encoding during reappraisal of reward anticipation.

    Science.gov (United States)

    Staudinger, Markus R; Erk, Susanne; Walter, Henrik

    2011-11-01

    Recent research showed that cognitive emotion regulation (ER) both increases activity in the dorsolateral prefrontal cortex (DLPFC) and decreases striatal responsivity to monetary rewards. Using a mixed monetary incentive delay/memory task as well as functional magnetic resonance imaging, we tested in healthy subjects whether ER effectively attenuates striatal reward encoding during the anticipation of reward (€1.00 vs. €0.05 reward cues) as well as subsequent target reaction times (RTs), which are an indicator of motivation to obtain reward. ER significantly diminished feelings of pleasant anticipation and slowed down €1.00 target RT. At the neural level, ER increased activity in the DLPFC and attenuated reward encoding in the left putamen. Analyses of psychophysiological interaction revealed that DLPFC activity correlated more positively with putamen activity during €0.05 than during €1.00 reward trials. Furthermore, parametric modulations showed that anticipatory left putamen activity correlated with target RT during nonregulation. No such correlation could be observed during ER, suggesting that ER had abolished preparatory target RT encoding. Our results provide evidence that ER can attenuate behavioral and striatal measures of reward-related motivation and motor preparation. Furthermore, the present findings suggest that the DLPFC might contribute to successful regulation of reward via increased promotion of low-reward responses.

  6. When opportunity meets motivation: Neural engagement during social approach is linked to high approach motivation.

    Science.gov (United States)

    Radke, Sina; Seidel, Eva-Maria; Eickhoff, Simon B; Gur, Ruben C; Schneider, Frank; Habel, Ute; Derntl, Birgit

    2016-02-15

    Social rewards are processed by the same dopaminergic-mediated brain networks as non-social rewards, suggesting a common representation of subjective value. Individual differences in personality and motivation influence the reinforcing value of social incentives, but it remains open whether the pursuit of social incentives is analogously supported by the neural reward system when positive social stimuli are connected to approach behavior. To test for a modulation of neural activation by approach motivation, individuals with high and low approach motivation (BAS) completed implicit and explicit social approach-avoidance paradigms during fMRI. High approach motivation was associated with faster implicit approach reactions as well as a trend for higher approach ratings, indicating increased approach tendencies. Implicit and explicit positive social approach was accompanied by stronger recruitment of the nucleus accumbens, middle cingulate cortex, and (pre-)cuneus for individuals with high compared to low approach motivation. These results support and extend prior research on social reward processing, self-other distinctions and affective judgments by linking approach motivation to the engagement of reward-related circuits during motivational reactions to social incentives. This interplay between motivational preferences and motivational contexts might underlie the rewarding experience during social interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Conflict Resolution as Near-Threshold Decision-Making: A Spiking Neural Circuit Model with Two-Stage Competition for Antisaccadic Task.

    Science.gov (United States)

    Lo, Chung-Chuan; Wang, Xiao-Jing

    2016-08-01

    Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pro- versus anti-response, our model incorporates a sensorimotor remapping module, and an action-selection module endowed with a "Stop" process through tonic inhibition. Both are under the modulation of rule-dependent control. We tested the model by applying it to the well known antisaccade task in which one must suppress the urge to look toward a visual target that suddenly appears, and shift the gaze diametrically away from the target instead. We found that the two-stage competition is crucial for reproducing the complex behavior and neuronal activity observed in the antisaccade task across multiple brain regions. Notably, our model demonstrates two types of errors: fast and slow. Fast errors result from failing to inhibit the quick automatic responses and therefore exhibit very short response times. Slow errors, in contrast, are due to incorrect decisions in the remapping process and exhibit long response times comparable to those of correct antisaccade responses. The model thus reveals a circuit mechanism for the empirically observed slow errors and broad distributions of erroneous response times in antisaccade. Our work suggests that selecting between competing automatic and voluntary actions in behavioral control can be understood in terms of near-threshold decision-making, sharing a common recurrent (attractor) neural circuit mechanism with discrimination in perception.

  8. Addiction: Beyond dopamine reward circuitry

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-13

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  9. Addiction: beyond dopamine reward circuitry.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Fowler, Joanna S; Tomasi, Dardo; Telang, Frank

    2011-09-13

    Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

  10. The interaction of bayesian priors and sensory data and its neural circuit implementation in visually guided movement.

    Science.gov (United States)

    Yang, Jin; Lee, Joonyeol; Lisberger, Stephen G

    2012-12-05

    Sensory-motor behavior results from a complex interaction of noisy sensory data with priors based on recent experience. By varying the stimulus form and contrast for the initiation of smooth pursuit eye movements in monkeys, we show that visual motion inputs compete with two independent priors: one prior biases eye speed toward zero; the other prior attracts eye direction according to the past several days' history of target directions. The priors bias the speed and direction of the initiation of pursuit for the weak sensory data provided by the motion of a low-contrast sine wave grating. However, the priors have relatively little effect on pursuit speed and direction when the visual stimulus arises from the coherent motion of a high-contrast patch of dots. For any given stimulus form, the mean and variance of eye speed covary in the initiation of pursuit, as expected for signal-dependent noise. This relationship suggests that pursuit implements a trade-off between movement accuracy and variation, reducing both when the sensory signals are noisy. The tradeoff is implemented as a competition of sensory data and priors that follows the rules of Bayesian estimation. Computer simulations show that the priors can be understood as direction-specific control of the strength of visual-motor transmission, and can be implemented in a neural-network model that makes testable predictions about the population response in the smooth eye movement region of the frontal eye fields.

  11. The interaction of Bayesian priors and sensory data and its neural circuit implementation in visually-guided movement

    Science.gov (United States)

    Yang, Jin; Lee, Joonyeol; Lisberger, Stephen G.

    2012-01-01

    Sensory-motor behavior results from a complex interaction of noisy sensory data with priors based on recent experience. By varying the stimulus form and contrast for the initiation of smooth pursuit eye movements in monkeys, we show that visual motion inputs compete with two independent priors: one prior biases eye speed toward zero; the other prior attracts eye direction according to the past several days’ history of target directions. The priors bias the speed and direction of the initiation of pursuit for the weak sensory data provided by the motion of a low-contrast sine wave grating. However, the priors have relatively little effect on pursuit speed and direction when the visual stimulus arises from the coherent motion of a high-contrast patch of dots. For any given stimulus form, the mean and variance of eye speed co-vary in the initiation of pursuit, as expected for signal-dependent noise. This relationship suggests that pursuit implements a trade-off between movement accuracy and variation, reducing both when the sensory signals are noisy. The tradeoff is implemented as a competition of sensory data and priors that follows the rules of Bayesian estimation. Computer simulations show that the priors can be understood as direction specific control of the strength of visual-motor transmission, and can be implemented in a neural-network model that makes testable predictions about the population response in the smooth eye movement region of the frontal eye fields. PMID:23223286

  12. Dynamic changes in single unit activity and γ oscillations in a thalamocortical circuit during rapid instrumental learning.

    Directory of Open Access Journals (Sweden)

    Chunxiu Yu

    Full Text Available The medial prefrontal cortex (mPFC and mediodorsal thalamus (MD together form a thalamocortical circuit that has been implicated in the learning and production of goal-directed actions. In this study we measured neural activity in both regions simultaneously, as rats learned to press a lever to earn food rewards. In both MD and mPFC, instrumental learning was accompanied by dramatic changes in the firing patterns of the neurons, in particular the rapid emergence of single-unit neural activity reflecting the completion of the action and reward delivery. In addition, we observed distinct patterns of changes in the oscillatory LFP response in MD and mPFC. With learning, there was a significant increase in theta band oscillations (6-10 Hz in the MD, but not in the mPFC. By contrast, gamma band oscillations (40-55 Hz increased in the mPFC, but not in the MD. Coherence between these two regions also changed with learning: gamma coherence in relation to reward delivery increased, whereas theta coherence did not. Together these results suggest that, as rats learned the instrumental contingency between action and outcome, the emergence of task related neural activity is accompanied by enhanced functional interaction between MD and mPFC in response to the reward feedback.

  13. Food reward, hyperphagia, and obesity.

    Science.gov (United States)

    Berthoud, Hans-Rudolf; Lenard, Natalie R; Shin, Andrew C

    2011-06-01

    Given the unabated obesity problem, there is increasing appreciation of expressions like "my eyes are bigger than my stomach," and recent studies in rodents and humans suggest that dysregulated brain reward pathways may be contributing not only to drug addiction but also to increased intake of palatable foods and ultimately obesity. After describing recent progress in revealing the neural pathways and mechanisms underlying food reward and the attribution of incentive salience by internal state signals, we analyze the potentially circular relationship between palatable food intake, hyperphagia, and obesity. Are there preexisting individual differences in reward functions at an early age, and could they be responsible for development of obesity later in life? Does repeated exposure to palatable foods set off a cascade of sensitization as in drug and alcohol addiction? Are reward functions altered by secondary effects of the obese state, such as increased signaling through inflammatory, oxidative, and mitochondrial stress pathways? Answering these questions will significantly impact prevention and treatment of obesity and its ensuing comorbidities as well as eating disorders and drug and alcohol addiction.

  14. Decoding the formation of reward predictions across learning.

    Science.gov (United States)

    Kahnt, Thorsten; Heinzle, Jakob; Park, Soyoung Q; Haynes, John-Dylan

    2011-10-12

    The predicted reward of different behavioral options plays an important role in guiding decisions. Previous research has identified reward predictions in prefrontal and striatal brain regions. Moreover, it has been shown that the neural representation of a predicted reward is similar to the neural representation of the actual reward outcome. However, it has remained unknown how these representations emerge over the course of learning and how they relate to decision making. Here, we sought to investigate learning of predicted reward representations using functional magnetic resonance imaging and multivariate pattern classification. Using a pavlovian conditioning procedure, human subjects learned multiple novel cue-outcome associations in each scanning run. We demonstrate that across learning activity patterns in the orbitofrontal cortex, the dorsolateral prefrontal cortex (DLPFC), and the dorsal striatum, coding the value of predicted rewards become similar to the patterns coding the value of actual reward outcomes. Furthermore, we provide evidence that predicted reward representations in the striatum precede those in prefrontal regions and that representations in the DLPFC are linked to subsequent value-based choices. Our results show that different brain regions represent outcome predictions by eliciting the neural representation of the actual outcome. Furthermore, they suggest that reward predictions in the DLPFC are directly related to value-based choices.

  15. Reward, Addiction, Withdrawal to Nicotine

    Science.gov (United States)

    De Biasi, Mariella; Dani, John A.

    2011-01-01

    Nicotine is the principle addictive component that drives continued tobacco use despite users’ knowledge of the harmful consequences. The initiation of addiction involves the mesocorticolimbic dopamine system, which contributes to the processing of rewarding sensory stimuli during the overall shaping of successful behaviors. Acting mainly through nicotinic receptors containing the α4 and β2 subunits, often in combination with the α6 subunit, nicotine increases the firing rate and the phasic bursts by midbrain dopamine neurons. Neuroadaptations arise during chronic exposure to nicotine, producing an altered brain condition that requires the continued presence of nicotine to be maintained. When nicotine is removed, a withdrawal syndrome develops. The expression of somatic withdrawal symptoms depends mainly on the α5, α2, and β4 nicotinic subunits involving the epithalamic habenular complex and its targets. Thus, nicotine taps into diverse neural systems and an array of nicotinic acetylcholine receptor (nAChR) subtypes to influence reward, addiction, and withdrawal. PMID:21438686

  16. Prior fear conditioning and reward learning interact in fear and reward networks

    Directory of Open Access Journals (Sweden)

    Lisa eBulganin

    2014-03-01

    Full Text Available The ability to flexibly adapt responses to changes in the environment is important for survival. Previous research in humans separately examined the mechanisms underlying acquisition and extinction of aversive and appetitive conditioned responses. It is yet unclear how aversive and appetitive learning interact on a neural level during counterconditioning in humans. This functional magnetic resonance imaging (fMRI study investigated the interaction of fear conditioning and subsequent reward learning. In the first phase (fear acquisition, images predicted aversive electric shocks or no aversive outcome. In the second phase (counterconditioning, half of the CS+ and CS- were associated with monetary reward in the absence of electric stimulation. The third phase initiated reinstatement of fear through presentation of electric shocks, followed by CS presentation in the absence of shock or reward. Results indicate that participants were impaired at learning the reward contingencies for stimuli previously associated with shock. In the counterconditioning phase, prior fear association interacted with reward representation in the amygdala, where activation was decreased for rewarded compared to unrewarded CS- trials, while there was no reward-related difference in CS+ trials. In the reinstatement phase, an interaction of previous fear association and previous reward status was observed in a reward network consisting of substantia nigra / ventral tegmental area (SN/VTA, striatum and orbitofrontal cortex (OFC, where activation was increased by previous reward association only for CS- but not for CS+ trials. These findings suggest that during counterconditioning, prior fear conditioning interferes with reward learning, subsequently leading to lower activation of the reward network.

  17. Learning Contextual Reward Expectations for Value Adaptation.

    Science.gov (United States)

    Rigoli, Francesco; Chew, Benjamin; Dayan, Peter; Dolan, Raymond J

    2018-01-01

    Substantial evidence indicates that subjective value is adapted to the statistics of reward expected within a given temporal context. However, how these contextual expectations are learned is poorly understood. To examine such learning, we exploited a recent observation that participants performing a gambling task adjust their preferences as a function of context. We show that, in the absence of contextual cues providing reward information, an average reward expectation was learned from recent past experience. Learning dependent on contextual cues emerged when two contexts alternated at a fast rate, whereas both cue-independent and cue-dependent forms of learning were apparent when two contexts alternated at a slower rate. Motivated by these behavioral findings, we reanalyzed a previous fMRI data set to probe the neural substrates of learning contextual reward expectations. We observed a form of reward prediction error related to average reward such that, at option presentation, activity in ventral tegmental area/substantia nigra and ventral striatum correlated positively and negatively, respectively, with the actual and predicted value of options. Moreover, an inverse correlation between activity in ventral tegmental area/substantia nigra (but not striatum) and predicted option value was greater in participants showing enhanced choice adaptation to context. The findings help understanding the mechanisms underlying learning of contextual reward expectation.

  18. Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity

    Directory of Open Access Journals (Sweden)

    Mathieu Baudonnat

    2017-05-01

    Full Text Available Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R learning critically depends on the dorsal striatum (DS, spatial memory relies on the hippocampus (HPC. Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments.

  19. Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults.

    Directory of Open Access Journals (Sweden)

    Erika E Forbes

    Full Text Available Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings

  20. Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults.

    Science.gov (United States)

    Forbes, Erika E; Rodriguez, Eric E; Musselman, Samuel; Narendran, Rajesh

    2014-01-01

    Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant

  1. Amphetamine alters neural response to sucrose in healthy women.

    Science.gov (United States)

    Melrose, A James; Bailer, Ursula; Wierenga, Christina E; Bischoff-Grethe, Amanda; Paulus, Martin P; Kaye, Walter H

    2016-06-30

    Amphetamine, likely via action on the brain's dopaminergic systems, induces anorectic eating behavior and blunts dopaminergic midbrain activation to rewards. Past work has hypothesized that this blunted reward responsivity is a result of increasing tonic over phasic DA activity. We sought to extend past findings to sweet taste during fMRI following single-blind administration of dextroamphetamine and placebo in 11 healthy women. We hypothesized that neural response in both limbic and cognitive sweet taste circuits would mirror past work with monetary rewards by effectively blunting sweet taste reward, and 'equalizing' it's rewarding taste with receipt of water. Behavioral results showed that amphetamine reduced self-reported hunger (supporting the existence of amphetamine anorexia) and increased self-report euphoria. In addition, region of Interest analysis revealed significant treatment by taste interactions in the middle insula and dorsal anterior cingulate confirming the 'equalizing' hypothesis in the cingulate, but unlike monetary reinforcers, the insula actually evinced enhanced separation between tastes on the amphetamine day. These results suggest a divergence from prior research using monetary reinforcers when extended to primary reinforcers, and may hint that altering dopaminergic signaling in the insula and anterior cingulate may be a target for pharmacological manipulation of appetite, and the treatment of obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Time Discounting for Primary Rewards

    National Research Council Canada - National Science Library

    McClure, Samuel M; Ericson, Keith M; Laibson, David I; Loewenstein, George; Cohen, Jonathan D

    2007-01-01

    Previous research, involving monetary rewards, found that limbic reward-related areas show greater activity when an intertemporal choice includes an immediate reward than when the options include only delayed rewards...

  3. Distinct Roles for the Amygdala and Orbitofrontal Cortex in Representing the Relative Amount of Expected Reward.

    Science.gov (United States)

    Saez, Rebecca A; Saez, Alexandre; Paton, Joseph J; Lau, Brian; Salzman, C Daniel

    2017-07-05

    The same reward can possess different motivational meaning depending upon its magnitude relative to other rewards. To study the neurophysiological mechanisms mediating assignment of motivational meaning, we recorded the activity of neurons in the amygdala and orbitofrontal cortex (OFC) of monkeys during a Pavlovian task in which the relative amount of liquid reward associated with one conditioned stimulus (CS) was manipulated by changing the reward amount associated with a second CS. Anticipatory licking tracked relative reward magnitude, implying that monkeys integrated information about recent rewards to adjust the motivational meaning of a CS. Upon changes in relative reward magnitude, neural responses to reward-predictive cues updated more rapidly in OFC than amygdala, and activity in OFC but not the amygdala was modulated by recent reward history. These results highlight a distinction between the amygdala and OFC in assessing reward history to support the flexible assignment of motivational meaning to sensory cues. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Posttraining ablation of adult-generated olfactory granule cells degrades odor-reward memories.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Akers, Katherine G; Guskjolen, Axel; Sakaguchi, Masanori; Josselyn, Sheena A; Frankland, Paul W

    2014-11-19

    Proliferation of neural progenitor cells in the subventricular zone leads to the continuous generation of new olfactory granule cells (OGCs) throughout life. These cells synaptically integrate into olfactory bulb circuits after ∼2 weeks and transiently exhibit heightened plasticity and responses to novel odors. Although these observations suggest that adult-generated OGCs play important roles in olfactory-related memories, global suppression of olfactory neurogenesis does not typically prevent the formation of odor-reward memories, perhaps because residual OGCs can compensate. Here, we used a transgenic strategy to selectively ablate large numbers of adult-generated OGCs either before or after learning in mice. Consistent with previous studies, pretraining ablation of adult-generated OGCs did not prevent the formation of an odor-reward memory, presumably because existing OGCs can support memory formation in their absence. However, ablation of a similar cohort of adult-generated OGCs after training impaired subsequent memory expression, indicating that if these cells are available at the time of training, they play an essential role in subsequent expression of odor-reward memories. Memory impairment was associated with the loss of adult-generated OGCs that were >10 d in age and did not depend on the developmental stage in which they were generated, suggesting that, once sufficiently mature, OGCs generated during juvenility and adulthood play similar roles in the expression of odor-reward memories. Finally, ablation of adult-generated OGCs 1 month after training did not produce amnesia, indicating that adult-generated OGCs play a time-limited role in the expression of odor-reward memories. Copyright © 2014 the authors 0270-6474/14/3415793-11$15.00/0.

  5. Are extremes of consumption in eating disorders related to an altered balance between reward and inhibition?

    Directory of Open Access Journals (Sweden)

    Christina E Wierenga

    2014-12-01

    Full Text Available The primary defining characteristic of a diagnosis of an eating disorder (ED is the disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food (DSM V; American Psychiatric Association, 2013. There is a spectrum, ranging from those who severely restrict eating and become emaciated on one end to those who binge and overconsume, usually accompanied by some form of compensatory behaviors, on the other. How can we understand reasons for such extremes of food consummatory behaviors? Recent work on obesity and substance use disorders has identified behaviors and neural pathways that play a powerful role in human consummatory behaviors. That is, corticostriatal limbic and dorsal cognitive neural circuitry can make drugs and food rewarding, but also engage self-control mechanisms that may inhibit their use. Importantly, there is considerable evidence that alterations of these systems also occur in ED. This paper explores the hypothesis that an altered balance of reward and inhibition contributes to altered extremes of response to salient stimuli, such as food. We will review recent studies that show altered sensitivity to reward and punishment in ED, with evidence of altered activity in corticostriatal and insula processes with respect to monetary gains or losses, and tastes of palatable foods. We will also discuss evidence for a spectrum of extremes of inhibition and dysregulation behaviors in ED supported by studies suggesting that this is related to top-down self-control mechanisms. The lack of a mechanistic understanding of ED has thwarted efforts for evidence-based approaches to develop interventions. Understanding how ED behavior is encoded in neural circuits would provide a foundation for developing more specific and effective treatment approaches.

  6. Pavlovian reward prediction and receipt in schizophrenia: relationship to anhedonia.

    Directory of Open Access Journals (Sweden)

    Erin C Dowd

    Full Text Available Reward processing abnormalities have been implicated in the pathophysiology of negative symptoms such as anhedonia and avolition in schizophrenia. However, studies examining neural responses to reward anticipation and receipt have largely relied on instrumental tasks, which may confound reward processing abnormalities with deficits in response selection and execution. 25 chronic, medicated outpatients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging using a pavlovian reward prediction paradigm with no response requirements. Subjects passively viewed cues that predicted subsequent receipt of monetary reward or non-reward, and blood-oxygen-level-dependent signal was measured at the time of cue presentation and receipt. At the group level, neural responses to both reward anticipation and receipt were largely similar between groups. At the time of cue presentation, striatal anticipatory responses did not differ between patients and controls. Right anterior insula demonstrated greater activation for nonreward than reward cues in controls, and for reward than nonreward cues in patients. At the time of receipt, robust responses to receipt of reward vs. nonreward were seen in striatum, midbrain, and frontal cortex in both groups. Furthermore, both groups demonstrated responses to unexpected versus expected outcomes in cortical areas including bilateral dorsolateral prefrontal cortex. Individual difference analyses in patients revealed an association between physical anhedonia and activity in ventral striatum and ventromedial prefrontal cortex during anticipation of reward, in which greater anhedonia severity was associated with reduced activation to money versus no-money cues. In ventromedial prefrontal cortex, this relationship held among both controls and patients, suggesting a relationship between anticipatory activity and anhedonia irrespective of diagnosis. These findings suggest that in the absence of

  7. Measuring circuits

    CERN Document Server

    Graf, Rudolf F

    1996-01-01

    This series of circuits provides designers with a quick source for measuring circuits. Why waste time paging through huge encyclopedias when you can choose the topic you need and select any of the specialized circuits sorted by application?This book in the series has 250-300 practical, ready-to-use circuit designs, with schematics and brief explanations of circuit operation. The original source for each circuit is listed in an appendix, making it easy to obtain additional information.Ready-to-use circuits.Grouped by application for easy look-up.Circuit source listings

  8. Oscillator circuits

    CERN Document Server

    Graf, Rudolf F

    1996-01-01

    This series of circuits provides designers with a quick source for oscillator circuits. Why waste time paging through huge encyclopedias when you can choose the topic you need and select any of the specialized circuits sorted by application?This book in the series has 250-300 practical, ready-to-use circuit designs, with schematics and brief explanations of circuit operation. The original source for each circuit is listed in an appendix, making it easy to obtain additional information.Ready-to-use circuits.Grouped by application for easy look-up.Circuit source listing

  9. Mindfulness training applied to addiction therapy: insights into the neural mechanisms of positive behavioral change

    Directory of Open Access Journals (Sweden)

    Garl

    2016-07-01

    Full Text Available Eric L Garland,1,2 Matthew O Howard,3 Sarah E Priddy,1 Patrick A McConnell,4 Michael R Riquino,1 Brett Froeliger4 1College of Social Work, 2Hunstsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; 3School of Social Work, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA Abstract: Dual-process models from neuroscience suggest that addiction is driven by dysregulated interactions between bottom-up neural processes underpinning reward learning and top-down neural functions subserving executive function. Over time, drug use causes atrophy in prefrontally mediated cognitive control networks and hijacks striatal circuits devoted to processing natural rewards in service of compulsive seeking of drug-related reward. In essence, mindfulness-based interventions (MBIs can be conceptualized as mental training programs for exercising, strengthening, and remediating these functional brain networks. This review describes how MBIs may remediate addiction by regulating frontostriatal circuits, thereby restoring an adaptive balance between these top-down and bottom-up processes. Empirical evidence is presented suggesting that MBIs facilitate cognitive control over drug-related automaticity, attentional bias, and drug cue reactivity, while enhancing responsiveness to natural rewards. Findings from the literature are incorporated into an integrative account of the neural mechanisms of mindfulness-based therapies for effecting positive behavior change in the context of addiction recovery. Implications of our theoretical framework are presented with respect to how these insights can inform the addiction therapy process. Keywords: mindfulness, frontostriatal, savoring, cue reactivity, hedonic dysregulation, reward, addiction

  10. Markov reward processes

    Science.gov (United States)

    Smith, R. M.

    1991-01-01

    Numerous applications in the area of computer system analysis can be effectively studied with Markov reward models. These models describe the behavior of the system with a continuous-time Markov chain, where a reward rate is associated with each state. In a reliability/availability model, upstates may have reward rate 1 and down states may have reward rate zero associated with them. In a queueing model, the number of jobs of certain type in a given state may be the reward rate attached to that state. In a combined model of performance and reliability, the reward rate of a state may be the computational capacity, or a related performance measure. Expected steady-state reward rate and expected instantaneous reward rate are clearly useful measures of the Markov reward model. More generally, the distribution of accumulated reward or time-averaged reward over a finite time interval may be determined from the solution of the Markov reward model. This information is of great practical significance in situations where the workload can be well characterized (deterministically, or by continuous functions e.g., distributions). The design process in the development of a computer system is an expensive and long term endeavor. For aerospace applications the reliability of the computer system is essential, as is the ability to complete critical workloads in a well defined real time interval. Consequently, effective modeling of such systems must take into account both performance and reliability. This fact motivates our use of Markov reward models to aid in the development and evaluation of fault tolerant computer systems.

  11. Driver circuit

    Science.gov (United States)

    Matsumoto, Raymond T. (Inventor); Higashi, Stanley T. (Inventor)

    1976-01-01

    A driver circuit which has low power requirements, a relatively small number of components and provides flexibility in output voltage setting. The driver circuit comprises, essentially, two portions which are selectively activated by the application of input signals. The output signal is determined by which of the two circuit portions is activated. While each of the two circuit portions operates in a manner similar to silicon controlled rectifiers (SCR), the circuit portions are on only when an input signal is supplied thereto.

  12. Corticostriatal circuit mechanisms of value-based action selection: Implementation of reinforcement learning algorithms and beyond.

    Science.gov (United States)

    Morita, Kenji; Jitsev, Jenia; Morrison, Abigail

    2016-09-15

    Value-based action selection has been suggested to be realized in the corticostriatal local circuits through competition among neural populations. In this article, we review theoretical and experimental studies that have constructed and verified this notion, and provide new perspectives on how the local-circuit selection mechanisms implement reinforcement learning (RL) algorithms and computations beyond them. The striatal neurons are mostly inhibitory, and lateral inhibition among them has been classically proposed to realize "Winner-Take-All (WTA)" selection of the maximum-valued action (i.e., 'max' operation). Although this view has been challenged by the revealed weakness, sparseness, and asymmetry of lateral inhibition, which suggest more complex dynamics, WTA-like competition could still occur on short time scales. Unlike the striatal circuit, the cortical circuit contains recurrent excitation, which may enable retention or temporal integration of information and probabilistic "soft-max" selection. The striatal "max" circuit and the cortical "soft-max" circuit might co-implement an RL algorithm called Q-learning; the cortical circuit might also similarly serve for other algorithms such as SARSA. In these implementations, the cortical circuit presumably sustains activity representing the executed action, which negatively impacts dopamine neurons so that they can calculate reward-prediction-error. Regarding the suggested more complex dynamics of striatal, as well as cortical, circuits on long time scales, which could be viewed as a sequence of short WTA fragments, computational roles remain open: such a sequence might represent (1) sequential state-action-state transitions, constituting replay or simulation of the internal model, (2) a single state/action by the whole trajectory, or (3) probabilistic sampling of state/action. Copyright © 2016. Published by Elsevier B.V.

  13. Addiction and brain reward and antireward pathways.

    Science.gov (United States)

    Gardner, Eliot L

    2011-01-01

    Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly), and that they enhance the functioning of the reward circuitry of the brain (producing the 'high' that the drug user seeks). The core reward circuitry consists of an 'in-series' circuit linking the ventral tegmental area, nucleus accumbens and ventral pallidum via the medial forebrain bundle. Although originally believed to simply encode the set point of hedonic tone, these circuits are now believed to be functionally far more complex, also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. 'Hedonic dysregulation' within these circuits may lead to addiction. The 'second-stage' dopaminergic component in this reward circuitry is the crucial addictive-drug-sensitive component. All addictive drugs have in common that they enhance (directly or indirectly or even transsynaptically) dop-aminergic reward synaptic function in the nucleus accumbens. Drug self-administration is regulated by nucleus accumbens dopamine levels, and is done to keep nucleus accumbens dopamine within a specific elevated range (to maintain a desired hedonic level). For some classes of addictive drugs (e.g. opiates), tolerance to the euphoric effects develops with chronic use. Postuse dysphoria then comes to dominate reward circuit hedonic tone, and addicts no longer use drugs to get high, but simply to get back to normal ('get straight'). The brain circuits mediating the pleasurable effects of addictive drugs are anatomically, neurophysiologically and neurochemically different from those mediating physical dependence, and from those mediating craving and relapse. There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain-reward mechanisms in such a manner as to impart vulnerability to addiction. In short, the 'bio-psycho-social' model of

  14. Metabolic activation of amygdala, lateral septum and accumbens circuits during food anticipatory behavior.

    Science.gov (United States)

    Olivo, Diana; Caba, Mario; Gonzalez-Lima, Francisco; Rodríguez-Landa, Juan F; Corona-Morales, Aleph A

    2017-01-01

    When food is restricted to a brief fixed period every day, animals show an increase in temperature, corticosterone concentration and locomotor activity for 2-3h before feeding time, termed food anticipatory activity. Mechanisms and neuroanatomical circuits responsible for food anticipatory activity remain unclear, and may involve both oscillators and networks related to temporal conditioning. Rabbit pups are nursed once-a-day so they represent a natural model of circadian food anticipatory activity. Food anticipatory behavior in pups may be associated with neural circuits that temporally anticipate feeding, while the nursing event may produce consummatory effects. Therefore, we used New Zealand white rabbit pups entrained to circadian feeding to investigate the hypothesis that structures related to reward expectation and conditioned emotional responses would show a metabolic rhythm anticipatory of the nursing event, different from that shown by structures related to reward delivery. Quantitative cytochrome oxidase histochemistry was used to measure regional brain metabolic activity at eight different times during the day. We found that neural metabolism peaked before nursing, during food anticipatory behavior, in nuclei of the extended amygdala (basolateral, medial and central nuclei, bed nucleus of the stria terminalis), lateral septum and accumbens core. After pups were fed, however, maximal metabolic activity was expressed in the accumbens shell, caudate, putamen and cortical amygdala. Neural and behavioral activation persisted when animals were fasted by two cycles, at the time of expected nursing. These findings suggest that metabolic activation of amygdala-septal-accumbens circuits involved in temporal conditioning may contribute to food anticipatory activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Cannabinoid modulation of drug reward and the implications of marijuana legalization.

    Science.gov (United States)

    Covey, Dan P; Wenzel, Jennifer M; Cheer, Joseph F

    2015-12-02

    Marijuana is the most popular illegal drug worldwide. Recent trends indicate that this may soon change; not due to decreased marijuana use, but to an amendment in marijuana's illegal status. The cannabinoid type 1 (CB1) receptor mediates marijuana's psychoactive and reinforcing properties. CB1 receptors are also part of the brain endocannabinoid (eCB) system and support numerous forms of learning and memory, including the conditioned reinforcing properties of cues predicting reward or punishment. This is accomplished via eCB-dependent alterations in mesolimbic dopamine function, which plays an obligatory role in reward learning and motivation. Presynaptic CB1 receptors control midbrain dopamine neuron activity and thereby shape phasic dopamine release in target regions, particularly the nucleus accumbens (NAc). By also regulating synaptic input to the NAc, CB1 receptors modulate NAc output onto downstream neurons of the basal ganglia motor circuit, and thereby support goal-directed behaviors. Abused drugs promote short- and long-term adaptations in eCB-regulation of mesolimbic dopamine function, and thereby hijack neural systems related to the pursuit of rewards to promote drug abuse. By pharmacologically targeting the CB1 receptors, marijuana has preferential access to this neuronal system and can potently alter eCB-dependent processing of reward-related stimuli. As marijuana legalization progresses, greater access to this drug should increase the utility of marijuana as a research tool to better understand the eCB system, which has the potential to advance cannabinoid-based treatments for drug addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. The Sensitivity of the Crayfish Reward System to Mammalian Drugs of Abuse

    Directory of Open Access Journals (Sweden)

    Adam T. Shipley

    2017-12-01

    Full Text Available The idea that addiction occurs when the brain is not able to differentiate whether specific reward circuits were triggered by adaptive natural rewards or falsely activated by addictive drugs exist in several models of drug addiction. The suitability of crayfish (Orconectes rusticus for drug addiction research arises from developmental variation of growth, life span, reproduction, behavior and some quantitative traits, especially among isogenic mates reared in the same environment. This broad spectrum of traits makes it easier to analyze the effect of mammalian drugs of abuse in shaping behavioral phenotype. Moreover, the broad behavioral repertoire allows the investigation of self-reinforcing circuitries involving appetitive and exploratory motor behavior, while the step-wise alteration of the phenotype by metamorphosis allows accurate longitudinal analysis of different behavioral states. This paper reviews a series of recent experimental findings that evidence the suitability of crayfish as an invertebrate model system for the study of drug addiction. Results from these studies reveal that unconditioned exposure to mammalian drugs of abuse produces a variety of stereotyped behaviors. Moreover, if presented in the context of novelty, drugs directly stimulate exploration and appetitive motor patterns along with molecular processes for drug conditioned reward. Findings from these studies indicate the existence of drug sensitive circuitry in crayfish that facilitates exploratory behavior and appetitive motor patterns via increased incentive salience of environmental stimuli or by increasing exploratory motor patterns. This work demonstrates the potential of crayfish as a model system for research into the neural mechanisms of addiction, by contributing an evolutionary, comparative context to our understanding of natural reward as an important life-sustaining process.

  17. Academic staff reward

    African Journals Online (AJOL)

    User

    structures and management systems. As a result, many universities are rethinking their reward strategies to better align them with the new realities in order to improve teaching staff motivation and retention. This study was conducted to identify academic staff reward related problems and to examine the effectiveness of both ...

  18. Academic staff reward

    African Journals Online (AJOL)

    User

    has a major role to play in achieving the objectives of the institution. ... Exceptionally, well motivated academic staff can, with appropriate ... significance attributed to the work. **To perform at their best, most individuals need to have financial or other extrinsic rewards tied to their performance. Rewards. Intrinsic*. Extrinsic**.

  19. Reward Merit with Praise.

    Science.gov (United States)

    Andrews, Hans A.

    1987-01-01

    Describes the efforts of two educational institutions to reward teaching excellence using positive feedback rather than merit pay incentives. An Arizona district, drawing on Herzberg's motivation theories, offers highly individualized rewards ranging from computers to conference money, while an Illinois community college bestows engraved plaques…

  20. Neural correlates of eating disorders: translational potential

    Directory of Open Access Journals (Sweden)

    McAdams CJ

    2015-09-01

    Full Text Available Carrie J McAdams,1,2 Whitney Smith1 1University of Texas at Southwestern Medical Center, 2Department of Psychiatry, Texas Health Presbyterian Hospital of Dallas, Dallas, TX, USA Abstract: Eating disorders are complex and serious psychiatric illnesses whose etiology includes psychological, biological, and social factors. Treatment of eating disorders is challenging as there are few evidence-based treatments and limited understanding of the mechanisms that result in sustained recovery. In the last 20 years, we have begun to identify neural pathways that are altered in eating disorders. Consideration of how these pathways may contribute to an eating disorder can provide an understanding of expected responses to treatments. Eating disorder behaviors include restrictive eating, compulsive overeating, and purging behaviors after eating. Eating disorders are associated with changes in many neural systems. In this targeted review, we focus on three cognitive processes associated with neurocircuitry differences in subjects with eating disorders such as reward, decision-making, and social behavior. We briefly examine how each of these systems function in healthy people, using Neurosynth meta-analysis to identify key regions commonly implicated in these circuits. We review the evidence for disruptions of these regions and systems in eating disorders. Finally, we describe psychiatric and psychological treatments that are likely to function by impacting these regions. Keywords: anorexia nervosa, bulimia nervosa, social cognition, reward processing, decision-making

  1. Brain-machine interface circuits and systems

    CERN Document Server

    Zjajo, Amir

    2016-01-01

    This book provides a complete overview of significant design challenges in respect to circuit miniaturization and power reduction of the neural recording system, along with circuit topologies, architecture trends, and (post-silicon) circuit optimization algorithms. The introduced novel circuits for signal conditioning, quantization, and classification, as well as system configurations focus on optimized power-per-area performance, from the spatial resolution (i.e. number of channels), feasible wireless data bandwidth and information quality to the delivered power of implantable system.

  2. Reward loss and addiction: Opportunities for cross-pollination.

    Science.gov (United States)

    Ortega, Leonardo A; Solano, José L; Torres, Carmen; Papini, Mauricio R

    2017-03-01

    Paradigms used to study the response to and consequences of exposure to reward loss have been underutilized in approaches to the psychobiology of substance use disorders. We propose here that bringing these two areas into contact will help expanding our understanding of both reward loss and addictive behavior, hence opening up opportunities for cross-pollination. This review focuses on two lines of research that point to parallels. First, several neurochemical systems involved in addiction are also involved in the modulation of the behavioral effects of reward loss, including opioid, GABA, and dopamine receptors. Second, there are extensive overlaps in the brain circuitry underlying both reward loss and addiction. Common components of this system include, at least, the amygdala, ventral and dorsal striatum, and various prefrontal cortex regions. Four emerging avenues of research that benefit from emphasis on the common ground between reward loss and addiction are reviewed, namely, the neural circuitry involved in reward devaluation, the influence of genetic and reward history on the behavioral vulnerability and resilience, the role of competing natural rewards, and emotional self-medication. An understanding of the role of reward loss in addiction will point to a deeper understanding of the initiation and maintenance of substance use disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Activation of dorsal raphe serotonin neurons is necessary for waiting for delayed rewards.

    Science.gov (United States)

    Miyazaki, Kayoko W; Miyazaki, Katsuhiko; Doya, Kenji

    2012-08-01

    The forebrain serotonergic system is a crucial component in the control of impulsive behaviors. We previously reported that the activity of serotonin neurons in the midbrain dorsal raphe nucleus increased when rats performed a task that required them to wait for delayed rewards. However, the causal relationship between serotonin neural activity and the tolerance for the delayed reward remained unclear. Here, we test whether the inhibition of serotonin neural activity by the local application of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin in the dorsal raphe nucleus impairs rats' tolerance for delayed rewards. Rats performed a sequential food-water navigation task that required them to visit food and water sites alternately via a tone site to get rewards at both sites after delays. During the short (2 s) delayed reward condition, the inhibition of serotonin neural activity did not significantly influence the numbers of reward choice errors (nosepoke at an incorrect reward site following a conditioned reinforcer tone), reward wait errors (failure to wait for the delayed rewards), or total trials (sum of reward choice errors, reward wait errors, and acquired rewards). By contrast, during the long (7-11 s) delayed reward condition, the number of wait errors significantly increased while the numbers of total trials and choice errors did not significantly change. These results indicate that the activation of dorsal raphe serotonin neurons is necessary for waiting for long delayed rewards and suggest that elevated serotonin activity facilitates waiting behavior when there is the prospect of forthcoming rewards.

  4. Anticipation of monetary and social reward differently activates mesolimbic brain structures in men and women.

    Science.gov (United States)

    Spreckelmeyer, Katja N; Krach, Sören; Kohls, Gregor; Rademacher, Lena; Irmak, Arda; Konrad, Kerstin; Kircher, Tilo; Gründer, Gerhard

    2009-06-01

    Motivation for goal-directed behaviour largely depends on the expected value of the anticipated reward. The aim of the present study was to examine how different levels of reward value are coded in the brain for two common forms of human reward: money and social approval. To account for gender differences 16 male and 16 female participants performed an incentive delay task expecting to win either money or positive social feedback. fMRI recording during the anticipation phase revealed proportional activation of neural structures constituting the human reward system for increasing levels of reward, independent of incentive type. However, in men activation in the prospect of monetary rewards encompassed a wide network of mesolimbic brain regions compared to only limited activation for social rewards. In contrast, in women, anticipation of either incentive type activated identical brain regions. Our findings represent an important step towards a better understanding of motivated behaviour by taking into account individual differences in reward valuation.

  5. Sleep deprivation amplifies striatal activation to monetary reward.

    Science.gov (United States)

    Mullin, B C; Phillips, M L; Siegle, G J; Buysse, D J; Forbes, E E; Franzen, P L

    2013-10-01

    Sleep loss produces abnormal increases in reward seeking but the mechanisms underlying this phenomenon are poorly understood. The present study examined the influence of one night of sleep deprivation on neural responses to a monetary reward task in a sample of late adolescents/young adults. Using a within-subjects crossover design, 27 healthy, right-handed late adolescents/young adults (16 females, 11 males; mean age 23.1 years) underwent functional magnetic resonance imaging (fMRI) following a night of sleep deprivation and following a night of normal sleep. Participants’ recent sleep history was monitored using actigraphy for 1 week prior to each sleep condition. Following sleep deprivation, participants exhibited increased activity in the ventral striatum (VS) and reduced deactivation in the medial prefrontal cortex (mPFC) during the winning of monetary reward, relative to the same task following normal sleep conditions. Shorter total sleep time over the five nights before the sleep-deprived testing condition was associated with reduced deactivation in the mPFC during reward. These findings support the hypothesis that sleep loss produces aberrant functioning in reward neural circuitry, increasing the salience of positively reinforcing stimuli. Aberrant reward functioning related to insufficient sleep may contribute to the development and maintenance of reward dysfunction-related disorders, such as compulsive gambling, eating, substance abuse and mood disorders.

  6. An update on the role of serotonin and its interplay with dopamine for reward

    NARCIS (Netherlands)

    Fischer, A.G.; Ullsperger, M.

    2017-01-01

    The specific role of serotonin and its interplay with dopamine in adaptive, reward guided behavior as well as drug dependence, still remains elusive. Recently, novel methods allowed cell type specific anatomical, functional, and interventional analyses of serotonergic and dopaminergic circuits,

  7. Neurochemical and behavioral indices of exercise reward are independent of exercise controllability

    OpenAIRE

    Herrera, Jonathan J.; Fedynska, Sofiya; Ghasem, Parsa R; Wieman, Tyler; Clark, Peter J.; Gray, Nathan; Loetz, Esteban; Campeau, Serge; Fleshner, Monika; Greenwood, Benjamin N.

    2016-01-01

    Brain reward circuits are implicated in stress-related psychiatric disorders. Exercise reduces the incidence of stress-related disorders, but the contribution of exercise reward to stress resistance is unknown. Exercise-induced stress resistance is independent of exercise controllability; both voluntary and forced wheel running protect rats against anxiety- and depression-like behavioral consequences of stress. Voluntary exercise is a natural reward, but whether rats find forced wheel running...

  8. Reward Processing by the Dorsal Raphe Nucleus: 5-HT and Beyond

    Science.gov (United States)

    Luo, Minmin; Zhou, Jingfeng; Liu, Zhixiang

    2015-01-01

    The dorsal raphe nucleus (DRN) represents one of the most sensitive reward sites in the brain. However, the exact relationship between DRN neuronal activity and reward signaling has been elusive. In this review, we will summarize anatomical, pharmacological, optogenetics, and electrophysiological studies on the functions and circuit mechanisms of…

  9. State dependent cortico-amygdala circuit dysfunction in bipolar disorder.

    Science.gov (United States)

    Brady, Roscoe O; Masters, Grace A; Mathew, Ian T; Margolis, Allison; Cohen, Bruce M; Öngür, Dost; Keshavan, Matcheri

    2016-09-01

    Existing models of the pathophysiology of bipolar disorder posit disruption in neural circuits of emotion regulation and reward processing. However, few fMRI studies have compared regional brain activity and connectivity in different mood states in bipolar disorder to determine if manic symptomatology is reflected in specific circuit abnormalities. The purpose of this study was to test the hypothesis that bipolar mania is associated with altered connectivity between cortical regions thought to regulate subcortical structures such as the amygdala and striatum. 28 subjects with bipolar disorder in a manic state, 24 different bipolar subjects in a euthymic state, and 23 matched healthy comparison subjects underwent resting state fMRI scans. Several cortical and sub-cortical structures implicated in the pathogenesis of bipolar disorder were selected for study. We conducted a whole-brain analysis of functional connectivity of these regions. Bipolar mania was differentiated from euthymia by decreased functional connectivity between the amygdala and anterior cingulate cortex (ACC). Mania was also characterized by increased connectivity between amygdala and dorsal frontal cortical structures that are normally anti-correlated in emotion regulation tasks. Both groups of bipolar subjects were prescribed medications. The study was not longitudinal in design. Compared to bipolar subjects in a euthymic state, subjects in the manic state demonstrate disrupted functional connectivity between brain regions involved in the regulation of emotion and the amygdala. This disruption of activity in neural circuits involved in emotion may underlie the emotional dysregulation inherent to a bipolar manic episode. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. A Voltage Mode Memristor Bridge Synaptic Circuit with Memristor Emulators

    Directory of Open Access Journals (Sweden)

    Leon Chua

    2012-03-01

    Full Text Available A memristor bridge neural circuit which is able to perform signed synaptic weighting was proposed in our previous study, where the synaptic operation was verified via software simulation of the mathematical model of the HP memristor. This study is an extension of the previous work advancing toward the circuit implementation where the architecture of the memristor bridge synapse is built with memristor emulator circuits. In addition, a simple