Structural and Functional Connectivity of Large-Scale Brain Networks in Autism

描述(申请人提供)：这项旨在促进神经科学研究多样性的职业发展奖的长期目标是发展候选人在应用新的大脑网络方法研究神经发育障碍和进行临床评估方面的技能，以便她能够成为神经成像和自闭症研究领域的独立研究员。具体地说，候选人将发展专业知识，将扩散张量成像(DTI)数据与最近开发的多变量模式分类和功能磁共振成像(FMRI)数据的有效连通性分析相结合，以检查自闭症谱系障碍(ASD)儿童非典型行为和认知背后的结构和内在功能大脑连通性。为此，候选人将接受神经成像、工程学、临床心理学、神经学和精神病学领域的专家的指导和培训。应聘者还将获得成功处理ASD儿童所需的临床评估方面的重要经验。此外，应聘者将承担正式的课程工作，并参加功能神经成像、临床心理学和计算机编程方面的研讨会，以实现这一目标。候选人提出的研究项目将使人们能够获得在发展认知神经科学领域成为一名成功的独立研究者所需的技能。ASD是一种病因不明的复杂神经发育障碍，其特征是社交沟通障碍、兴趣受限、重复和刻板行为。这项拟议的研究的主要目标是检查ASD儿童非典型认知和行为背后的异常结构和功能脑连接。候选人建议使用DTI和fMRI来探索大规模的大脑网络，以检查患有ASD的儿童在网络之间的动态相互作用中可能存在的异常皮质连接和妥协。她将专门测试她提出的一种新的系统水平假说，将大脑网络连接方面的最新进展与自闭症神经成像研究的融合证据综合起来。假说是，在处理社会刺激的过程中，前脑岛的活动不足导致ASD患者的显著检测能力降低，从而损害了对认知至关重要的其他大规模大脑网络之间的动态切换。此外，她将探索建立基于大脑的生物标记物的方法，以区分患有自闭症儿童和通常发育中的儿童，使用大脑连通性测量以及认知和行为测量的组合。这项研究项目和培训计划的完成将使Uddin博士能够熟练地实现她成为自闭症和神经成像研究领域的独立研究员的目标，还将促进ASD大脑网络功能障碍生物标记物的原则性开发。这一职业发展奖与NIH促进神经科学研究多样性的目标是一致的。)

DESCRIPTION (provided by applicant): The long-term objective of this Career Development Award to Promote Diversity in Neuroscience Research is to develop the candidate's skills in applying novel brain network approaches to the study of neurodevelopmental disorders, and in conducting clinical assessments, so that she can become an independent investigator in the fields of neuroimaging and autism research. Specifically, the candidate will develop expertise in using diffusion tensor imaging (DTI) data in conjunction with recently developed multivariate pattern classification and effective connectivity analyses of functional magnetic resonance imaging (fMRI) data to examine structural and intrinsic functional brain connectivity underlying atypical behavior and cognition in children with autism spectrum disorders (ASD). To this end, the candidate will be mentored and trained by experts in the fields of neuroimaging, engineering, clinical psychology, neurology and psychiatry. The candidate will also gain critical experience in clinical assessments necessary for successfully working with children with ASD. In addition, the candidate will undertake formal coursework and attend seminars in functional neuroimaging, clinical psychology, and computer programming to achieve this goal. The research project proposed by the candidate will enable the acquisition of the skills required to become a successful independent investigator in the field of developmental cognitive neuroscience. ASD is a complex neurodevelopmental disorder of largely unknown etiology, characterized by social communicative impairments, restricted interests, and repetitive and stereotyped behaviors. The main goal of the proposed research is to examine aberrant structural and functional brain connectivity underlying atypical cognition and behavior in children with ASD. The candidate proposes to probe large-scale brain networks using DTI and fMRI to examine possible aberrant cortical connectivity and compromises in dynamic interactions between networks in children with ASD. She will specifically test a novel systems-level hypothesis she has put forth, synthesizing recent advances in brain network connectivity with converging evidence from neuroimaging studies in autism. The hypothesis is that hypoactivity of the anterior insula during processing of social stimuli results in reduced salience detection in individuals with ASD, which impairs dynamic switching between other large-scale brain networks important for cognition. Additionally, she will explore methods to establish brain-based biomarkers to distinguish children with ASD from typically developing children using a combination of brain connectivity measures and cognitive and behavioral measures. Completion of this research project and training plan will enable Dr. Uddin to gain proficiency relevant to her goal of becoming an independent investigator in the fields of autism and neuroimaging research, and will also facilitate the principled development of biomarkers of brain network dysfunction in ASD. This Career Development Award is consistent with the NIH goals to promote diversity in neuroscience research. )