Neural Circuitry of Social Cognition in the Broad Autism Phenotype

描述（由申请人提供）：15年多来，我们的研究团队采用了Kanner关于自闭症患者父母行为特征的原始观察结果，并制定了标准化，有效和可靠的临床措施来定义现在被称为广泛自闭症表型（BAP）。BAP被认为代表了自闭症个体的非自闭症亲属中自闭症潜在遗传易感性的表型表达，并且由较温和但与自闭症的定义特征定性相似的特征定义。在我们目前的BAP自闭症研究中心，我们已经确定了社会认知的异常（在以前的研究中与社会认知神经回路中的特定大脑区域相关的任务），这些异常在具有BAP社会行为特征的“自闭症父母”中更常见（即，孤独症父母的孤独症儿童的孤独症患病率（即孤独症父母的孤独症患病率）高于无孤独症父母或社区对照组。我们已经开发了功能磁共振成像范例，以确定自闭症社会认知神经回路关键组成部分的异常（杏仁核、上级颞沟和梭状回），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-气泡方法，该方法允许我们整合眼睛跟踪数据、皮肤电导反应、和BOLD反应的功能磁共振成像，以分离出哪些面部特征驱动行为，自主神经和神经的社会信息从面孔的歧视。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措施来表征自闭症患者的父母异常的社会认知的神经回路，并阐明在BAP中出现功能失调的社会认知的信息处理阶段。该应用程序是三名研究人员的合作，他们在自闭症和BAP（J. Piven at Pennsylvania）、社会认知功能磁共振成像（G.麦卡锡在杜克），和新的方法来阐明社会认知的神经基础（R。Adolphs at Caltech）。如本申请中所提出的，对BAP的社会行为成分的行为和神经机制的研究将为自闭症大脑和行为表型的形式障碍提供重要的新见解，用于自闭症和BAP的未来遗传学、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.