Neuronal Basis of Vicarious Reinforcement Dysfunction in Autism Spectrum Disorder

自闭症谱系障碍替代强化功能障碍的神经元基础

基本信息

批准号：
8598108
负责人：
MICHAEL L PLATT
金额：
$ 30.98万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-21 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8598108
关键词：
Animal Model Anterior Attention Behavior Behavioral Model Brain Brain imaging Caring Cervical Code Computers Cues Data Disease Electric Stimulation Ethics Functional disorder Growth Human Impairment Individual Investigation Learning Lesion Macaca mulatta Measures Mediating Modeling Monkeys National Institute of Mental Health Neurons Neurophysiology - biologic function Operant Conditioning Outcome Oxytocin Pattern Penetration Process Psychological reinforcement Puncture procedure Punishment Reaction Time Reference Values Rewards Saline Shapes Signal Transduction Social Interaction Techniques Testing Therapeutic Intervention Variant Visual Work autism spectrum disorder base cingulate cortex classical conditioning electrical microstimulation experience gaze improved insight learned behavior microstimulation motivated behavior network dysfunction neural circuit neuromechanism neurophysiology neuropsychiatry preference response social

项目摘要

Despite a broad continuum of phenotypic variation in behavior, individuals with autism spectrum disorders (ASD) share core deficits in social interaction. Here we propose that social dysfunction in ASD results, in part, from impairments in deriving vicarious reinforcement from others. Observing what happens to others powerfully shapes normal human learning and behavior. Such other-regarding outcomes can drive observational learning, and motivate behaviors such as cooperation, as well as envy. Empathic responses associated with vicarious reward appear early in ontogeny, and their impairment in neuropsychiatric disorders like ASD can have devastating consequences. Understanding and treating social dysfunction in ASD will be advanced by discovering and manipulating the neural mechanisms that derive vicarious reward and punishment from what happens to others. Although brain-imaging studies have revealed some of the neural circuitry mediating social interactions, the neuronal mechanisms underlying vicarious reward remain unknown. We will use our new behavioral model of vicarious reward to determine the underlying neuronal mechanisms, delineate the impacts of network dysfunction due to reversible inactivation of ACC or OFC on vicarious reward and other-regarding behavior, and define the effects of oxytocin (OT), a potential therapeutic intervention for ASD, on behavior and neural function.

尽管行为的表型变化存在广泛的连续性，但自闭症谱系障碍（ASD）的个体在社会互动中具有核心缺陷。在这里，我们提出，ASD结果中的社会功能障碍在某种程度上是由于从其他人那里衍生出替代性增强方面的损害。观察他人发生的事情会有力地塑造正常的人类学习和行为。这样的其他成果可以推动观察性学习，并激励诸如合作和嫉妒之类的行为。与替代奖励相关的移情反应出现在本体发育中，并且它们在ASD等神经精神疾病中的损害可能会带来毁灭性的后果。通过发现和操纵神经机制，从他人发生的事情中获得替代性的奖励和惩罚，可以提高ASD中的社会功能障碍的理解和治疗。尽管大脑成像的研究揭示了一些介导社交相互作用的神经回路，但替代性奖励的神经元机制仍然未知。我们将使用我们的新行为模型来确定潜在的神经元机制，描绘由于ACC或OFC对替代奖励和其他偏向行为的可逆失活而导致的网络功能障碍的影响，并定义了氧气（OT）的影响（OT），这是一种潜在的治疗性介入的介入介绍性介入的行为和神经性行为和神经性行为和神经性和神经功能。