Neural Circuitry of Social Cognition in the Broad Autism Phenotype

描述（由申请人提供）：15年来，我们的研究团队采用了Kanner对一些自闭症患者父母的行为特征的原始观察，并开发了标准化、有效和可靠的临床测量方法来定义现在被称为广义自闭症表型（BAP）。BAP被认为代表了自闭症患者的非自闭症亲属对自闭症潜在遗传倾向性的表型表达，其特征较为温和，但在质量上与自闭症的定义特征相似。在我们目前的UNC STAART自闭症研究中心，我们已经确定了社会认知异常（在先前研究中与社会认知神经回路中特定大脑区域相关的任务中），这些异常在具有BAP社会行为特征（即冷漠人格）的“自闭症父母”中比在没有冷漠人格或社区控制的“自闭症父母”中更常见。我们已经开发了功能磁共振成像范式来识别自闭症社会认知神经回路的关键组成部分（杏仁核、颞上沟和梭状回）的异常，并开发了一种新的方法来探测来自面部的社会信息的复杂处理——气泡法，它允许我们在功能磁共振成像上整合眼动追踪数据、皮肤电导反应和BOLD反应的同时测量，以分离面部的哪些特征驱动行为。从面部识别社会信息的自主和神经辨别。在这个修订后的应用程序中，我们建议使用功能磁共振成像，神经心理学，行为和心理生理学的测量来表征自闭症个体父母的异常社会认知的神经回路，并阐明在BAP中出现功能障碍社会认知的信息加工阶段。这个应用程序是三位研究者的合作，他们在自闭症和BAP（北卡罗来纳大学的J. Piven），社会认知的功能磁共振成像（杜克大学的G. McCarthy）和阐明社会认知的神经基础的新方法（加州理工学院的R. Adolphs）方面有着良好的合作记录和互补经验。研究BAP的社会行为成分的行为和神经机制，将为自闭症大脑和行为表型的形成提供重要的新见解，用于未来自闭症和BAP的遗传学、大脑和行为研究。

DESCRIPTION (provided by applicant): For over 15 years, our research team has taken Kanner's original observations about behavioral features characteristic of some parents of autistic individuals and developed standardized, valid, and reliable clinical measures to define what is now referred to as the Broad Autism Phenotype (BAP). The BAP is thought to represent the phenotypic expression of the underlying genetic liability to autism in non-autistic relatives of autistic individuals and is defined by characteristics that are milder but qualitatively similar to the defining features of autism. In our current UNC STAART Autism Research Center, we have identified abnormalities of social cognition (on tasks linked in previous studies to specific brain regions in the neural circuitry of social cognition) that occur more commonly in 'autism parents' with the social behavioral characteristics of the BAP (i.e., aloof personality) than in either 'autism parents' without aloof personality or community controls. We have developed fMRI paradigms that identify abnormalities in key components of the neural circuitry of social cognition in autism (amygdala, superior temporal sulcus, and fusiform gyrus) and developed a novel approach for probing the complex processing of social information from faces - the Bubbles Method that allows us to integrate simultaneous measurement of eye tracking data, skin conductance response, and BOLD responses on fMRI to isolate which features of the face drive behavioral, autonomic, and neural discrimination of social information from faces. In this revised application, we propose to use fMRI, neuropsychological, behavioral, and psychophysiological measures to characterize the neural circuitry of abnormal social cognition in parents of autistic individuals and to elucidate the stage of information processing at which dysfunctional social cognition arises in the BAP. This application is a collaboration of three investigators with a track record of collaboration and complementary experience in autism and the BAP (J. Piven at UNC), fMRI of social cognition (G. McCarthy at Duke), and novel approaches to elucidating the neural basis of social cognition (R. Adolphs at Caltech). Study of the behavioral and neural mechanisms underlying the social behavioral component of the BAP, as proposed in this application, will provide important new insights into the forme fruste of the autism brain and behavioral phenotype for use in future genetics, brain, and behavioral studies of autism and the BAP.