Connectivity in social brain systems in autism

描述(申请人提供)：自闭症谱系障碍(ASD)是以大脑为基础的发育障碍，但其特定的神经基础尚不清楚。对ASD的社会脑理论和互联性理论进行研究的结果喜忧参半，反映了临床表型的异质性。这项申请建议开发新的实验和分析方法来检查特定大脑系统内的连接，这些系统从属于ASD中的社会信息处理。这种创新的实验方法结合了动态和静态刺激，能够提取反映人脸感知和动作感知系统各个阶段的事件相关电位(ERPs)和振荡脑电(EEG)活动。一种尖端的分析方法应用结构方程建模(SEM)来测试提出的社交大脑这些方面和相关社会功能之间的连接性模型(通过标准化的行为评估和现实世界行为的生态有效的父母报告测量进行评估)。这种开创性的方法将是第一次将扫描电子显微镜应用于ASD的电生理数据，提供了其他成像方法无法获得的连接性的时间方面的洞察。将测试有效连接的特定模型，并将使用扫描电子显微镜来探索替代模型，该模型可以解释ASD患者和典型参与者之间的差异，以及ASD内部的差异。这个项目的意义在于阐明了以前使用传统分析方法得到的不一致的结果；拟议的创新将提供新的工具，通过检查社会感知的各个阶段的功能以及神经系统的水平来解析自闭症的异质性。该项目需要具有互补专业知识的早期研究人员之间的合作，并与两个主要自闭症研究中心的现有研究项目协同；使用相同的程序和硬件汇集来自两个地点的电生理数据本身是一种后勤进步，有可能加快两个地点的研究步伐。拟议的扫描电子显微镜方法已经阐明了其他精神障碍中的基因-大脑-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两个地点的基因分型项目相结合。 与公共健康相关：这项研究通过检查支持面孔感知和模仿的大脑系统的完整性，研究自闭症社交困难的大脑基础。通过了解这些大脑回路中的连接模式，这项研究可能会揭示这种疾病的原因、在更年轻的时候识别这种疾病的方法以及治疗的途径。

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.