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

描述（由申请人提供）：促进神经科学研究多样性职业发展奖的长期目标是培养候选人应用新型脑网络方法研究神经发育障碍和进行临床评估的技能，使她能够成为神经影像和自闭症研究领域的独立研究者。具体来说，候选人将发展使用扩散张量成像（DTI）数据结合最近开发的多元模式分类和功能磁共振成像（fMRI）数据的有效连接分析的专业知识，以检查自闭症谱系障碍（ASD）儿童非典型行为和认知背后的结构和内在功能性大脑连接。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领域专家的指导和培训。候选人还将获得成功治疗自闭症儿童所需的临床评估的重要经验。此外，候选人将参加正式课程并参加功能神经影像、临床心理学和计算机编程研讨会，以实现这一目标。候选人提出的研究项目将能够获得成为发育认知神经科学领域成功的独立研究者所需的技能。自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，病因很大程度上未知，其特征是社交沟通障碍、兴趣受限以及重复和刻板行为。拟议研究的主要目标是检查自闭症儿童非典型认知和行为背后的异常结构和功能大脑连接。该候选人提议使用 DTI 和功能磁共振成像来探测大规模大脑网络，以检查自闭症儿童的大脑皮层连接可能存在的异常以及网络之间动态交互的妥协。她将专门测试她提出的一个新颖的系统级假设，综合大脑网络连接方面的最新进展和自闭症神经影像学研究的证据。该假设认为，在处理社会刺激过程中，前岛叶的活动减退会导致自闭症谱系障碍患者的显着性检测减少，从而损害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，她还将探索建立基于大脑的生物标志物的方法，结合大脑连接测量以及认知和行为测量，将患有自闭症谱系障碍的儿童与正常发育的儿童区分开来。该研究项目和培训计划的完成将使 Uddin 博士能够熟练掌握与她成为自闭症和神经影像研究领域的独立研究者的目标相关的知识，还将促进 ASD 脑网络功能障碍生物标志物的原则性开发。该职业发展奖与 NIH 促进神经科学研究多样性的目标一致。 ） 公共卫生相关性：自闭症谱系障碍 (ASD) 影响着 1:150 人，并且发病率持续稳步上升，使该疾病成为紧迫的公共卫生问题。自闭症谱系障碍会给患者及其家人带来终生的困难，而且目前还没有已知的治疗方法。最近开发的分析工具使得体内大脑连接研究成为可能，揭示了自闭症谱系障碍患者大脑组织的重要原理。大脑网络的完整性和功能作用以及它们之间的相互作用的表征将有助于我们了解自闭症谱系障碍患者潜在的大脑差异，并最终开发出更有效的治疗方法。 ）

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. )