EEG-Based Assessment of Functional Connectivity in Autism

描述(由申请人提供)：有大量数据表明，大脑连接改变是自闭症神经生物学的一个关键方面。然而，大脑连通性改变在自闭症核心损害产生中的作用还没有完全被了解。在自闭症的损害中，运动功能是神经生物学研究的极佳候选者。尤其是在自闭症中，实践异常是一个强有力的和重复的发现，并已被很好地描述为行为特征。此外，与复杂的交流和社会行为的许多方面相比，实践行为可以更容易地量化和实验控制。实践技能已被证明与沟通和社会行为的临床测量相关。此外，实践功能背后的大脑机制也得到了很好的理解。具体地说，皮质顶叶下部区域、运动前皮质区域以及两者之间的连接是实践功能所必需的。脑电(EEG)已经被成功地用于研究与实践相关的脑连通性，无论是有失用症还是没有失用症的成年人，然而它还没有被用于儿童或自闭症患者。目前申请中提出的这项研究将利用基于脑电的技术解决自闭症中大脑连接性改变的作用，并将这些神经生物学改变与运动能力受损以及社交和沟通能力受损联系起来。本研究的具体目的是(1)表征儿童辅助练习的功能网络；(2)揭示自闭症儿童在练习任务执行过程中大脑连通性的变化；(3)评估大脑连通性改变与运动能力、社交能力和沟通能力之间的关系。该项目是儿童神经科专业人员职业发展计划的一部分，目的是获得高级脑电信号分析、研究设计和系统神经科学方面的培训。肯尼迪·克里格研究所和约翰斯·霍普金斯大学拥有世界级的生物医学工程、生物统计学和临床系，为PI提供了一个特殊的环境，使其成为研究自闭症和其他神经发育障碍患者大脑行为关系的独立研究员。 与公共健康相关：一种理论认为，自闭症儿童大脑的不同区域不能有效地相互沟通。这项研究的目的是了解自闭症儿童大脑区域之间的交流与正常发育儿童相比有何不同。这些知识对于开发改变大脑区域交流方式的治疗方法至关重要。 公共卫生相关性：早产是一个主要的公共卫生问题，因为早产导致并归因于脑白质损伤而导致的显著神经发育延迟。目前还没有促进恢复和修复的治疗方法。该项目的目标是通过增强脑内内源性祖细胞的特定信号通路，促进脑白质损伤后遗症的细胞、代谢、生理和行为恢复。

DESCRIPTION (provided by applicant): There are substantial data to suggest that altered cerebral connectivity is a key aspect of the neurobiology of autism. Nevertheless, the role of altered cerebral connectivity in the production of the core impairments of autism has is not yet fully understood. Of the impairments in autism, motor function is an excellent candidate for neurobiological study. Praxis abnormalities in particular are a robust and replicated finding in autism and have been well characterized behaviorally. Additionally, praxis behavior can be more easily quantified and experimentally controlled than can many aspects of complex communicative and social behavior. Praxis skill has been shown to correlate with clinical measures of communicative and social behavior. Further, the cerebral mechanisms that underlie praxis function are well understood. Specifically, inferior cortical parietal regions, premotor cortical regions and the connectivity between the two are known to be necessary for praxis function. The electroencephalogram (EEG) has been used successfully to study cerebral connectivity associated with praxis in adults with and without apraxia, however it has not yet been employed in children or in individuals with autism. The research proposed in the current application will address the role of altered cerebral connectivity in autism using EEG-based techniques and will relate these neurobiological alterations to impaired motor performance and impaired social and communicative performance. The specific aims are (1) to characterize the functional network subserving praxis in children, (2) to demonstrate alterations of cerebral connectivity in children with autism during performance of praxis tasks, and (3) to assess the relationship between altered cerebral connectivity and motor, social and communicative ability. This project is proposed as part of a career development plan for the PI, a child neurologist, to obtain training in advanced EEG signal analysis, study design and systems neuroscience. The Kennedy Krieger Institute and Johns Hopkins University have world-class Biomedical Engineering, Biostatistics and clinical departments that provide an exceptional environment to enable the PI to become an independent investigator studying brain-behavior relationships in autism and other neurodevelopmental disabilities. PUBLIC HEALTH RELEVANCE: One theory says that different areas of the brain do not communicate with each other effectively in children with autism. The goal of this study is to understand how communication between brain regions differs in children with autism compared with typically developing children. This knowledge will be critical in order to develop treatments that alter the way brain regions communicate. PUBLIC HEALTH RELEVANCE: Preterm birth is a major public health concern due to significant neurodevelopmental delays that result and attributed to white matter injury in the brain. There are no therapies available that promote recovery and repair. The goal of this project is to promote cellular, metabolic, physiologic and behavior recovery of white matter injury sequelae by enhancing specific signaling pathways of endogenous progenitor cells in the brain.