Connectivity in social brain systems in autism

描述（由申请人提供）：自闭症谱系障碍（ASDs）是一种基于大脑的发育障碍，但其具体的神经基础尚不清楚。对ASD的社会脑理论和互联性理论的研究都得到了不同的结果，反映了临床表型的异质性。该应用程序提出了开发新的实验和分析方法，以检查ASD中服务于社会信息处理的特定大脑系统内的连通性。创新的实验方法结合了动态和静态刺激，能够提取事件相关电位（ERPs）和反映面部感知和动作感知系统阶段的振荡脑电图（EEG）活动。一种尖端的分析方法应用结构方程模型（SEM）来测试社会大脑的这些方面和相关社会功能之间的连接的拟议模型（通过标准化行为评估和生态有效的父母报告测量现实世界的行为）。这种开创性的方法将首次将扫描电镜应用于ASD的电生理数据，为其他成像方法无法获得的连接的时间方面提供见解。一个特定的有效连接模型将被测试，扫描电镜也将被用来探索可能解释ASD个体和典型参与者之间差异的替代模型，以及ASD内部的差异。本项目的意义在于阐明了以往工作中使用常规分析方法得到的不一致结果；提出的创新将通过检查社会感知各个阶段的功能以及神经系统水平，为分析ASD的异质性提供新的工具。该项目需要早期研究人员之间的合作，他们具有互补的专业知识，并与两个主要自闭症研究中心的现有研究项目协同合作；使用相同的程序和硬件从两个地点汇集电生理数据本身就是一种后勤上的进步，有可能加快两个地点的研究步伐。提出的扫描电镜方法已经阐明了其他精神疾病的基因-脑-行为关系，并将导致未来的研究将行为和电生理数据与正在进行的基因分型项目结合起来。

DESCRIPTION (provided by applicant): Autism spectrum disorders (ASDs) are brain-based developmental disorders, but their specific neural bases are not yet understood. Studies investigating both social brain theories and interconnectivity theories of ASD have obtained mixed results, reflecting the heterogeneity observed in the clinical phenotype. This application proposes to develop novel experimental and analytic approaches to examine connectivity within specific brain systems subserving social information processing in ASD. The innovative experimental method incorporates both dynamic and static stimuli, enabling extraction of both event-related potentials (ERPs) and oscillatory electroencephalographic (EEG) activity reflecting stages of face perception and action perception systems. A cutting-edge analytic approach applies structural equation modeling (SEM) to test a proposed model of connectivity among these facets of the social brain and related social function (assessed through standardized behavioral assessments and ecologically valid parent report measures of real-world behavior). This groundbreaking approach will be the first to apply SEM to electrophysiological data in ASD, providing insight into temporal aspects of connectivity inaccessible to other imaging methods. A specific model of effective connectivity will be tested, and SEM will also be employed to explore alternative models that may explain variance between individuals with ASD and typical participants, as well as variation within ASD. The significance of this project lies in elucidating the inconsistent results obtained by prior work using conventional analytic methods; the proposed innovations will provide new tools to parse heterogeneity in ASD by examining function at individual stages of social perception as well as the level of neural systems. The project entails collaboration between early stage investigators with complementary expertise and synergy with extant research programs at two major autism research centers; pooling of electrophysiological data from two sites using identical procedures and hardware is a logistical advance unto itself with the potential to accelerate the pace of research at both sites. The proposed SEM approach has elucidated gene-brain-behavior relationships in other psychiatric disorders and will lead to future research integrating behavioral and electrophysiological data with ongoing genotyping projects at both sites. PUBLIC HEALTH RELEVANCE: This research studies the brain bases for social difficulties in autism by examining the integrity of brain systems supporting face perception and imitation. By understanding patterns of connectivity in these brain circuits, the study may shed light on causes of the disorder, ways to identify the disorder at younger ages, and avenues for treatment.