Cognitive and Neural Flexibility in Autism

 描述（由申请人提供）：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1名患病。虽然已经取得了很大的进展，了解与疾病相关的社会和沟通缺陷的神经生物学，很少有人知道有关的神经生物学基础的限制和重复行为的ASD诊断的核心。目前项目的目标是了解认知灵活性和脑功能之间的关系，在诱发（任务）和内在（休息）状态的青年与ASD。认知灵活性，即在心理过程之间切换的能力，通常在ASD儿童中受损，其方式可能严重影响日常生活活动中的过渡。认知能力可能是ASD患者出现限制性和重复性行为的基础。了解ASD认知能力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儿童的连接模式动态范围或神经可感知性降低。拟议的研究将超越这些初步发现，并明确测试限制和重复行为的一个方面-认知能力-是否与ASD中相应的神经能力有关。评估脑功能和功能障碍的一种新方法是量化动态功能连接，或脑区域之间功能耦合的时变模式。这项研究的目标是实现三个目标：1）了解ASD儿童和TD儿童在诱发脑状态下认知灵活性的神经基础，2）了解ASD儿童和TD儿童在内在脑状态下认知灵活性的神经基础，以及3）调查诱发脑状态下激活模式之间的关系，内在大脑状态下的动态功能连接模式，以及ASD灵活性的行为测量。为了实现这些目标，该项目将实施传统的基于任务的功能性MRI，静息状态功能性MRI的动态功能连接分析，以及任务和静息状态功能性MRI与认知灵活性的行为测量的整合。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ASD中受影响的神经回路。由于行为不稳定性是自闭症患者难以进行护理的重要原因，因此这些发现可能会对ASD儿童及其护理人员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.