Cognitive and Neural Flexibility in Autism

 描述(申请人提供)：自闭症谱系障碍(ASD)是一种复杂的神经发育障碍，病因不明，每68名儿童中就有一人受到影响。虽然在了解与ASD相关的社交和沟通障碍的神经生物学方面取得了很大进展，但对ASD诊断中关键的限制性和重复行为的神经生物学基础知之甚少。目前项目的目标是了解患有和不患有自闭症的年轻人在诱发(任务)和内在(休息)状态下的认知灵活性和大脑功能之间的关系。认知灵活性，即在心理过程之间切换的能力，在自闭症儿童中经常受到损害，可能会严重影响日常生活活动中的过渡。认知不灵活可能是ASD出现限制性和重复性行为的基础。了解ASD认知不灵活的神经机制对于定制治疗方法来治疗这种研究不足但普遍存在的症状至关重要。PI最近发表了初步证据，表明ASD儿童的连接模式或神经缺乏的动态范围减少。这项拟议的研究将超越这些初步发现，明确测试受限和重复行为的一个方面--认知缺乏灵活性--是否与ASD的相应神经缺乏联系。一种评估大脑功能和功能障碍的新方法是量化动态功能连接，即大脑区域之间功能耦合的时变模式。本研究的目的有三个：1)了解ASD和TD儿童在诱发脑状态下认知灵活性的神经基础；2)了解ASD和TD儿童在内在脑状态下认知灵活性的神经基础；3)探讨ASD和TD儿童在诱发脑状态下的激活模式、内在脑状态下的动态功能连接模式和ASD中灵活性的行为测量之间的关系。为了实现这些目标，该项目将实施传统的基于任务的功能磁共振，静态功能磁共振的动态功能连通性分析，以及将任务和静息状态功能磁共振与认知灵活性的行为测量相结合。这项研究计划响应了机构间自闭症协调委员会的战略计划，以了解自闭症患者受到影响的神经回路。由于行为不灵活是导致自闭症患者CARIN困难的重要原因，这些发现可能会对ASD儿童及其照顾者的生活质量产生重大影响。

 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is a complex neurodevelopment disorder of largely unknown etiology affecting 1 in 68 children. While much progress has been made towards understanding the neurobiology of social and communication deficits associated with the disorder, very little is known regarding the neurobiological basis of restricted and repetitive behaviors central to the ASD diagnosis. The goal of the current project is to understand the relationship between cognitive flexibility and brain function during evoked (task) and intrinsic (resting) states in youth with and without ASD. Cognitive flexibility, the capacity to switch between mental processes, is often impaired in children with ASD in ways that can severely impact transitions during day-to- day activities of life. Cognitive inflexibilitymay underlie the emergence of restricted and repetitive behaviors in ASD. Understanding the neural mechanisms underlying cognitive inflexibility in ASD is critical for tailoring therapies to treat tis under-studied yet pervasive symptom. The PI has recently published preliminary evidence of reduced dynamic range of connectivity patterns, or neural inflexibility, in children with ASD. The proposed research will go beyond these preliminary findings and explicitly test whether one aspect of restricted and repetitive behaviors --cognitive inflexibility-- is linked with a corresponding neural inflexibility in ASD. A novel approach to assessing brain function and dysfunction is the quantification of dynamic functional connectivity, or time-varying patterns of functional coupling between brain regions. The goals of the study are to address three aims: 1) to understand the neural bases of cognitive flexibility in children with ASD and TD children during evoked brain states, 2) to understand the neural bases of cognitive flexibility in children with ASD and TD children during intrinsic brain states, and 3) to investigate relationships between activation patterns during evoked brain states, dynamic functional connectivity patterns during intrinsic brain states, and behavioral measures of flexibility in ASD. To address these aims, the project will implement traditional task- based functional MRI, dynamic functional connectivity analyses of resting-state fMRI, and integration of task and resting state fMRI with behavioral measures of cognitive flexibility. This program of research responds to the Interagency Autism Coordinating Committee's strategic plan to understand the neural circuitry that is affected in ASD. As behavioral inflexibility is an important cause of difficulties in carin for autistic individuals, these findings will potentially have a major impact on quality of life for children with ASD and their caregivers.