Biological and Information Processing Mechanisms Underlying Autism

描述(申请人提供)：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。它包括5个主题：1)自闭症是一种基本能力保持不变或增强的复杂信息处理能力的障碍；2)自闭症是一种大脑连接障碍，远距离连接不足和局部代偿性连接过度连接不足；3)自闭症是一种发育障碍，其大脑行为表现随着从儿童到成人的大脑成熟的每个阶段而改变；4)从潜在的信息处理机制来看，病理性社会障碍得到最好的理解；以及5)情绪和情感障碍是综合征的主要组成部分，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、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以及患有和不患有自闭症的儿童、青少年和成人群体。项目I：低功能和高功能自闭症的分类和面部知识的发展；项目II：情感接触障碍：情绪处理的大脑机制的发展；项目III：系统连接和大脑激活：语言和感知的成像研究；项目IV：扩散张量磁共振成像和大脑微结构和纤维通路的组织病理学。项目一侧重于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。项目二集中于阐明情绪处理机制和从童年到成年的成熟障碍；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。情绪性的基因修饰物也将被确定。项目III侧重于了解大脑功能连接的障碍，这些障碍是信息处理受损的基础，进而是自闭症患者认知和行为障碍的基础。该项目还包括对大脑如何识别和分类单词的创新机器学习研究，以及对大脑皮质功能的计算建模。项目IV着眼于特定脑白质通路的结构连通性和皮质内脑白质投射的组织病理学。该项目将有助于协调自闭症患者的功能连接不足和早期结构性过度生长。识别自闭症行为的基本信息处理机制将导致开发更具体和有效的干预措施；同样，识别连接性改变可以导致有针对性的认知干预，从而增加神经连接性。这项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。

DESCRIPTION (provided by applicant): 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.