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.

尽管行为表型变异广泛，但自闭症谱系障碍 (ASD) 患者在社交互动方面都存在核心缺陷。在这里，我们提出，自闭症谱系障碍患者的社会功能障碍部分是由于从他人那里获得替代强化的能力受损造成的。观察他人发生的事情可以有力地塑造人类正常的学习和行为。这种与他人有关的结果可以推动观察学习，并激发合作和嫉妒等行为。与替代奖励相关的共情反应出现在个体发育早期，它们在自闭症谱系障碍等神经精神疾病中的损害可能会产生毁灭性的后果。通过发现和操纵从他人身上发生的事情中获得替代奖励和惩罚的神经机制，可以促进对自闭症谱系障碍的社会功能障碍的理解和治疗。尽管脑成像研究揭示了一些介导社交互动的神经回路，但替代奖励背后的神经机制仍然未知。我们将使用新的替代奖励行为模型来确定潜在的神经元机制，描述由于 ACC 或 OFC 可逆失活而导致的网络功能障碍对替代奖励和其他相关行为的影响，并定义催产素 (OT) 的影响，对自闭症谱系障碍（ASD）行为和神经功能的潜在治疗干预。