Longitudinal Characterization of Functional Connectivity in Autism

描述(申请人提供)：本建议旨在促进Jeffrey Anderson博士的职业发展，作为一名独立研究员，对神经发育和神经精神障碍的功能MR连接进行纵向神经成像研究，特别是在自闭症功能连接异常方面的专业知识。虽然申请人在脑电生理学博士培训期间有丰富的指导研究经验，在功能成像方法方面有广泛的神经放射学培训，但他没有进行大型临床成像调查的经验，需要招募和评估患者以及对大型成像数据集进行多变量统计分析。这项提案的具体研究目的是培养这些技能 通过对自闭症患者功能连通性的纵向研究。现在有大量证据表明 自闭症患者存在大脑区域之间的功能连接异常，自闭症会在儿童和青春期持续发展。这些连接异常构成了一种识别自闭症亚型、预测预后和指导治疗的有前景的技术。然而，连接异常的机制仍不清楚。这项建议试图通过对自闭症患者功能连接性的纵向研究来确定连接性障碍是泛化的，还是局限于特定路径长度的连接，还是与特定的功能网络有关。纵向设计将允许评估这些连接异常是如何在儿童后期和青春期发展的，并将利用最大的高功能自闭症DTI成像数据集和从儿童晚期到成年早期的体积扫描，从而能够对大脑连接进行跨通道分析。该提案的长期目标是利用申请人在数学、神经科学和临床神经成像方面的综合培训，建立一个严谨、基础广泛的成像实验室，通过使用新的成像方法探测大脑网络中的功能连接异常，为神经疾病的诊断和理解做出重大贡献。 公共卫生相关性：这个项目寻求提供指导和专注的研究经验，以提供他领导神经发育和神经精神障碍功能连接的尖端纵向成像研究所需的技能。作为主要应用，将进行一项纵向研究，描述自闭症中功能连接异常的机制和分布，产生巨大的公共健康益处。

DESCRIPTION (provided by applicant): This proposal is designed to facilitate career development of Jeffrey Anderson, MD PhD as an independent investigator to conduct longitudinal neuroimaging studies of functional MR connectivity in neurodevelopmental and neuropsychiatric disorders, with particular expertise in functional connectivity abnormalities in autism. Although the applicant has extensive mentored research experience during PhD training in electrophysiology of the brain, and extensive neuroradiological training in functional imaging methods, he has not had experience conducting large clinical imaging investigations, requiring patient recruitment and assessment and multivariate statistical analysis of large imaging datasets. The specific research aims of this proposal develop these skills through a longitudinal study of functional connectivity in autism. There is now extensive evidence that functional connectivity abnormalities between brain regions are present in autism, which continue to develop through childhood and adolescence. These connectivity abnormalities comprise a promising technique for identifying autism subtypes, predicting prognosis, and guiding treatment. Yet the mechanism for connectivity abnormalities remains unknown. This proposal seeks to use a longitudinal investigation of functional connectivity in autism to establish whether connectivity disturbances are generalized, localized to connections of specific path length, or associated with specific functional networks. The longitudinal design will allow assessment of how these connectivity abnormalities develop through late childhood and adolescence, and will leverage the largest imaging dataset of high-functioning autism DTI and volumetric scans from late childhood to early adulthood, allowing cross-modality analysis of brain connectivity. Long term goals of the proposal are to leverage the applicant's combined training in mathematics, neuroscience, and clinical neuroimaging to build a rigorous, broad-based imaging laboratory that can make major contributions to diagnosis and understanding of neurological disorders by probing functional connectivity abnormalities in brain networks using novel imaging methods. PUBLIC HEALTH RELEVANCE: This project seeks to provide mentorship and focused research experience to provide skills necessary for him to lead cutting-edge longitudinal imaging investigations of functional connectivity in neurodevelopmental and neuropsychiatric disorders. As a primary application, a longitudinal study will be performed characterizing the mechanism and distribution of functional connectivity abnormalities in autism, yielding immense public health benefits.