Cognitive and Neural Flexibility in Autism

自闭症的认知和神经灵活性

• 批准号: 9329481
• 负责人: Lucina Qazi Uddin
• 金额: $ 47.43万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-08 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9329481
• 关键词: 12 year old; Address; Affect; Age; Aman; Anterior; Attention; Autistic Disorder; Behavioral; Brain; Brain region; Caregivers; Child; Cognition; Cognitive; Complex; Coupling; Cues; Data; Diagnosis; Dimensions; Disease; Early Intervention; Etiology; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Impairment; Incidence; Individual; Insula of Reil; Laboratories; Life; Link; Magnetic Resonance Imaging; Measures; Mental Processes; Neurobiology; Neurodevelopmental Disorder; Pattern; Performance; Prefrontal Cortex; Public Health; Publishing; Quality of life; Readiness; Reporting; Research; Rest; Severities; Stimulus; Strategic Planning; Symptoms; Task Performances; Testing; Time; Youth; attentional control; autism spectrum disorder; base; behavior measurement; behavioral impairment; flexibility; improved; innovation; neural circuit; neurodevelopment; neuroimaging; neuromechanism; novel; novel strategies; peer; programs; public health relevance; relating to nervous system; repetitive behavior; response; social communication; therapy design

 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.

 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，其病因很大程度上未知，每 68 名儿童中就有 1 人受到影响。虽然在理解与该疾病相关的社交和沟通缺陷的神经生物学方面已经取得了很大进展，但对于自闭症谱系障碍诊断的核心限制和重复行为的神经生物学基础却知之甚少。当前项目的目标是了解患有和不患有自闭症谱系障碍的青少年在诱发（任务）和内在（休息）状态下认知灵活性和大脑功能之间的关系。患有自闭症谱系障碍 (ASD) 的儿童的认知灵活性（即在心理过程之间进行切换的能力）通常会受到损害，从而严重影响日常生活活动中的转换。认知僵化可能是自闭症谱系障碍患者出现受限和重复行为的基础。了解自闭症谱系障碍认知僵化背后的神经机制对于制定疗法来治疗这种尚未得到充分研究但普遍存在的症状至关重要。 PI 最近发表了初步证据，表明患有自闭症谱系障碍 (ASD) 的儿童的连接模式动态范围减小，或神经不灵活。拟议的研究将超越这些初步发现，并明确测试限制性和重复性行为的一个方面——认知不灵活性——是否与自闭症谱系障碍中相应的神经不灵活性有关。评估大脑功能和功能障碍的一种新方法是对动态功能连接或大脑区域之间功能耦合的时变模式进行量化。该研究的目标是解决三个目标：1）了解 ASD 和 TD 儿童在诱发大脑状态期间认知灵活性的神经基础，2）了解 ASD 和 TD 儿童在内在大脑状态期间认知灵活性的神经基础，3）研究诱发大脑状态期间的激活模式、内在大脑状态期间的动态功能连接模式以及在 自闭症谱系障碍。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成像、静息态功能磁共振成像的动态功能连接分析，以及任务和静息态功能磁共振成像与认知灵活性行为测量的整合。该研究计划响应机构间自闭症协调委员会的战略计划，以了解自闭症谱系障碍中受影响的神经回路。由于行为僵化是自闭症患者护理困难的一个重要原因，这些发现可能会对自闭症儿童及其照顾者的生活质量产生重大影响。