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

描述（由申请人提供）：这个职业发展奖的长期目标，以促进神经科学研究的多样性是发展候选人的技能，在应用新的大脑网络方法的神经发育障碍的研究，并在进行临床评估，使她能够成为一个独立的调查员在神经影像学和自闭症研究领域。具体来说，候选人将开发专业知识，使用扩散张量成像（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，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与ASD儿童合作所需的临床评估方面的关键经验。此外，候选人将承担正式的课程，并参加功能性神经影像学，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使其获得成为发展认知神经科学领域成功的独立调查员所需的技能。ASD是一种复杂的神经发育障碍，其病因基本未知，其特征在于社交障碍，兴趣受限以及重复和刻板的行为。这项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大脑连接。候选人建议使用DTI和fMRI探测大规模的大脑网络，以检查ASD儿童网络之间动态相互作用的可能异常皮层连接和妥协。她将专门测试她提出的一个新的系统水平假设，综合大脑网络连接的最新进展和自闭症神经成像研究的证据。该假说认为，在处理社会刺激时，前额叶的活动减退导致ASD患者的显著性检测降低，这损害了对认知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，以使用大脑连接措施以及认知和行为措施的组合将ASD儿童与典型发育儿童区分开来。该研究项目和培训计划的完成将使Uddin博士获得与她成为自闭症和神经影像学研究领域独立研究者的目标相关的熟练程度，并将促进ASD脑网络功能障碍生物标志物的原则性发展。这个职业发展奖与NIH促进神经科学研究多样性的目标一致。) 公共卫生相关性：自闭症谱系障碍（ASD）影响1：150的个体，并且发病率继续稳步上升，使该障碍成为紧迫的公共卫生问题。ASD会给受影响的个人及其家庭带来终身的困难，并且没有已知的治疗方法。最近开发的分析工具使体内大脑连接的研究成为可能，揭示了ASD患者大脑组织的重要原则。表征大脑网络的完整性和功能作用，以及它们之间的相互作用，将有助于我们了解ASD患者的潜在大脑差异，并最终导致更有效的治疗和疗法的发展。)

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. )