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

描述（由申请人提供）：促进神经科学研究多样性的职业发展奖的长期目标是培养候选人在神经发育障碍研究中应用新颖的脑网络方法和进行临床评估的技能，使她能够成为神经影像学和自闭症研究领域的独立研究者。具体而言，该候选人将在使用弥散张量成像（DTI）数据结合最近开发的多变量模式分类和功能磁共振成像（fMRI）数据的有效连接分析方面发展专业知识，以检查自闭症谱系障碍（ASD）儿童非典型行为和认知的结构和内在功能脑连接。为此，候选人将接受神经影像学、工程学、临床心理学、神经病学和精神病学等领域专家的指导和培训。候选人还将获得临床评估的关键经验，这对于成功地与自闭症儿童一起工作是必要的。此外，候选人将参加功能性神经影像学、临床心理学和计算机编程方面的正式课程和研讨会，以实现这一目标。候选人提出的研究项目将使获得成为发展认知神经科学领域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，其特征是社会交流障碍、兴趣受限、重复和刻板行为。该研究的主要目的是研究ASD儿童非典型认知和行为背后的异常结构和功能脑连接。该候选人建议使用DTI和fMRI来探测大规模的大脑网络，以检查ASD儿童中可能的异常皮质连接和网络之间动态相互作用的妥协。她将专门测试她提出的一个新的系统级假设，将大脑网络连接的最新进展与自闭症神经影像学研究的融合证据综合起来。该假说认为，在处理社会刺激过程中，前脑岛的活动减少导致ASD患者显著性检测减少，这损害了对认知很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志物的方法，通过结合大脑连接测量和认知和行为测量来区分自闭症儿童和正常发育的儿童。该研究项目和培训计划的完成将使Uddin博士能够熟练掌握她的目标，成为自闭症和神经影像学研究领域的独立研究者，并将促进ASD脑网络功能障碍生物标志物的原则发展。这个职业发展奖与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. ) PUBLIC HEALTH RELEVANCE: Autism spectrum disorders (ASD) affect 1:150 individuals, and the incidence continues to rise steadily, making the disorder an urgent public health concern. ASD results in lifelong difficulties for afflicted individuals and their families, and there is no known cure. Recently developed analytic tools have enabled the study of brain connectivity in vivo, revealing important principles of brain organization in individuals with ASD. Characterization of the integrity and functional roles of brain networks, as well as interactions between them, will help us to understand the underlying brain differences in individuals with ASD and eventually lead to the development of more effective treatments and therapies. )