Neuronal Basis of Vicarious Reinforcement Dysfunction in Autism Spectrum Disorder

尽管在行为上存在广泛的表型变异，但自闭症谱系障碍（ASD）患者在社会交往中存在核心缺陷。在这里，我们提出，ASD的社会功能障碍的结果，部分原因是从别人那里获得替代强化的障碍。观察他人身上发生的事情会有力地塑造正常的人类学习和行为。这种与他人相关的结果可以推动观察学习，并激发合作和嫉妒等行为。与替代性奖励相关的移情反应出现在个体发育的早期，在ASD等神经精神疾病中，它们的损伤可能会产生毁灭性的后果。理解和治疗ASD的社会功能障碍将通过发现和操纵从发生在他人身上的事情中获得替代性奖励和惩罚的神经机制来推进。尽管脑成像研究已经揭示了一些调节社会互动的神经回路，但替代性奖励背后的神经机制仍然未知。我们将使用我们新的替代性奖励行为模型来确定潜在的神经机制，描述由于ACC或OFC可逆失活导致的网络功能障碍对替代性奖励和其他相关行为的影响，并定义催产素（OT）对行为和神经功能的影响，这是ASD的潜在治疗干预。

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.