Biological and Information Processing Mechanisms Underlying Autism

自闭症背后的生物和信息处理机制

• 批准号: 7904203
• 负责人: NANCY J MINSHEW
• 金额: $ 186.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-06 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904203
• 关键词: Biological; Information; Processing; Mechanisms; Underlying

This center focuses on elucidating fundamental information processing and neurobiological mechanisms causing autism. It incorporates 5 themes: 1) autism as a disorder of complex information processing abilities WITH intact or enhanced basic abilities; 2) autism as a disturbance in cerebral connectivity with under connectivity of long-distance connections and over-connectivity of compensatory local connections; 3) autism as a developmental disorder whose brain-behavioral manifestations change with each stage of brain maturation from childhood to adulthood; 4) that the pathognomonic social impairments are best understood in terms of underlying information processing mechanisms; and 5) that emotional and affective impairments are a major component of the syndrome and significant contributor to impaired function and serious behavior issues. These goals will be addressed using behavioral, cognitive, fMRI, DTI, DTT, and neuropathologic studies of: infant siblings, first-diagnosed toddlers with autism, and groups of children, adolescents, and adults with and without autism. Project I: Development of Categorization & Facial Knowledge in Low & High Functioning Autism; Project II: Disturbances of Affective Contact: Development of Brain Mechanisms for Emotion Processing; Project III: Systems Connectivity & Brain Activation: Imaging Studies of Language & Perception; Project IV: Diffusion Tensor MRI & Histopathology of Brain Microstructure & Fiber Pathways. Project I focuses on understanding the earliest manifestations of autism and the development of earlier diagnostic tools; it also focuses on information processing mechanisms underlying social and cognitive symptoms. Project II focuses on elucidating emotion processing mechanisms and the maturational disturbances from childhood through adulthood; these studies will clarify how individuals with autism experience, understand and regulate emotion, and will also examine their self-awareness of emotion. Genetic modifiers of emotionality will also be determined. Project III focuses on understanding disturbances in functional brain connectivity that underlie the impaired processing of information and in turn the cognitive and behavioral impairments in autism. The project also includes innovative machine-learning studies of how the brain identifies and categorizes words and computational modeling of cortical function. Project IV looks at structural connectivity of specific white matter pathways and the histopathology of intra-cortical white matter projections. This project will help reconcile the functional under-connectivity and early structural overgrowth in autism. The identification of fundamental information processing mechanisms underlying the behavior of autism will lead to the development of more specific and effective interventions; similarly identification of connectivity alterations can lead to targeted cognitive interventions that increase neural connectivity. This research addresses Autism Research Matrix goals # 1,2,3,6,16,17,19,22,23,26,31,and 34.

该中心致力于阐明导致自闭症的基本信息处理和神经生物学机制。它包含5个主题：1)自闭症是一种复杂信息处理能力障碍，基本能力完好或增强；2)自闭症是一种长距离连接连接不足、代偿性局部连接连接过度的大脑连接障碍；3)自闭症是一种发育障碍，其脑行为表现随儿童至成年脑成熟的各个阶段而变化；4)从潜在的信息加工机制角度来理解病态社会障碍是最好的；5)情绪和情感障碍是该综合征的主要组成部分，也是导致功能受损和严重行为问题的重要因素。这些目标将通过行为、认知、功能磁共振成像、DTI、DTT和神经病理学研究来解决：婴儿兄弟姐妹、首次诊断为自闭症的幼儿、儿童、青少年和患有和不患有自闭症的成年人群体。项目一：低、高功能自闭症患者分类与面部知识的发展项目二：情感接触障碍：情绪加工脑机制的发展；项目三：系统连接与大脑激活：语言与感知的成像研究；项目四：脑微结构及纤维通路弥散张量MRI及组织病理学。项目一的重点是了解自闭症的早期表现和早期诊断工具的开发；它还侧重于潜在的社会和认知症状的信息处理机制。项目二主要研究情绪加工机制和儿童期至成年期的成熟障碍；这些研究将阐明自闭症患者如何体验、理解和调节情绪，并将检查他们对情绪的自我意识。情绪的基因修饰因子也将被确定。项目III的重点是了解大脑功能连接的紊乱，这种紊乱是信息处理受损的基础，进而导致自闭症患者的认知和行为障碍。该项目还包括创新的机器学习研究，研究大脑如何识别和分类单词，以及皮质功能的计算建模。项目IV着眼于特定白质通路的结构连通性和皮层内白质投影的组织病理学。该项目将有助于协调自闭症的功能连接不足和早期结构过度生长。识别自闭症行为背后的基本信息处理机制将有助于开发更具体、更有效的干预措施；同样，识别连通性的改变可以导致有针对性的认知干预，增加神经连通性。本研究涉及自闭症研究矩阵目标# 1,2,3,6,16,17,19,22,23,26,31和34。