NEUROIMAGING OF SOCIAL AND COGNITIVE DEFICITS IN AUTISM

描述(申请人提供)：这个项目将使用结构(MRI)和功能(FMRI)神经成像技术来检查自闭症患者选定的社会认知、情感和执行功能缺陷以及仪式重复行为的神经基础。社会缺陷和仪式性重复行为是自闭症的定义特征，社会认知缺陷(例如，处理面部表情中反映的情绪和社会线索)和执行功能缺陷(例如，产生灵活的适合任务的动作，同时抑制不适合任务的动作)被认为是这些行为背后的关键神经心理过程。尽管在描述这些缺陷方面取得了进展，但它们的神经生物学基础在很大程度上仍然不为人知。我们建议通过四项研究来探索自闭症患者社会认知、情感和执行功能过程以及仪式性重复行为的神经回路，这些研究旨在：(1)描述自闭症中潜在的社会意向性推理的神经回路；(2)检查面部加工和欣赏的神经回路 (3)探索支持自闭症中任务适当/不适当行为的启动和抑制的神经回路，以及(4)表征额纹状体的结构完整性和发育，我们假设它与自闭症相关的仪式性重复行为有关。这些目标将在三项涉及高功能自闭症青少年和成年男性的功能磁共振研究中得到解决，并在一项针对自闭症儿童(2至4岁)样本中使用扩散张量成像的纵向研究中得到解决。这个项目在概念上与家庭研究项目、小鼠遗传学项目、脆性X项目和治疗项目相联系，在那里检查这些相同的过程，以及在同一样本自闭症患者中进行一项伴随的、单独资助的对这些神经心理过程的研究。该项目汇集了几位经验丰富的神经成像研究人员，他们是自闭症的新手，形成了开发神经成像研究的综合计划的基础，以表征自闭症神经回路中的关键元素。这些信息应该会加深我们对神经机制的理解，并完善我们对这种疾病的大脑和行为表型的概念。

DESCRIPTION (provided by applicant): This project will employ structural (MRI) and functional (fMRI) neuroimaging techniques to examine the neural basis of selected social cognitive, affective, and executive functioning deficits, and ritualistic-repetitive behaviors, in autism. Social deficits and ritualisticrepetitive behaviors are defining features of autism, and deficits in social cognition (e.g., processing emotional and social cues reflected in facial expressions) and executive function (e.g., generating flexible task-appropriate actions while inhibiting task-inappropriate ones) are considered key neuropsychological processes underlying these behaviors. Despite progress in describing these deficits, their neurobiological bases are still largely unknown. We propose to explore the neural circuitry of social cognitive, affective, and executive function processes and ritualistic-repetitive behaviors in autism in four studies designed to: (1) characterize the neural circuitry underlying inferences of social intentionality in autism, (2) examine neural circuitry underlying the processing and appreciation of facial expressions in autism, (3) explore the neural circuitry supporting the initiation and inhibition of taskappropriate/inappropriate behaviors in autism, and (4) characterize the structural integrity and development of frontal-striatal tracts, which we hypothesize to be involved in ritualistic-repetitive behaviors associated with autism. These aims will be addressed in three fMRI studies involving high functioning autistic adolescent and adult males, and in one longitudinal study employing diffusion tensor imaging in a sample of autistic children (ages 2- to 4-years). This project links conceptually to Family Study Project, Mouse Genetics Project, Fragile X Project, and Treatment Project, where these same processes are examined, as well as to a companion, separately funded study of these neuropsychological processes in this same sample of autistic individuals. This project brings together several experienced neuroimaging researchers, new to autism, forming the basis for the development of an integrated program of neuroimaging research to characterize key elements in the neural circuitry of autism. This information should further our understanding of the neural mechanisms as well as refine our notions of the brain and behavioral phenotypes in this disorder.