The neurobiological basis of heterogeneous social and motor deficits in ASD

自闭症谱系障碍（ASD）异质性社交和运动缺陷的神经生物学基础

• 批准号: 9035411
• 负责人: Lisa Sarah Aziz-Zadeh
• 金额: $ 42.39万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9035411
• 关键词: Address; Affect; Age; Apraxias; Area; Brain; Brain region; Child; Data; Development; Developmental Coordination Disorders; Diagnosis; Dimensions; Emotional; Emotions; Empathy; Ensure; Exhibits; Face; Functional Magnetic Resonance Imaging; Hand; Health; Heterogeneity; Impairment; Individual; Individual Differences; Inferior frontal gyrus; Intention; Knowledge; Link; Measures; Motor; Movement; Neurobiology; Neurologic; Parietal Lobe; Patients; Performance; Population; Process; Research; School-Age Population; Social Functioning; Symptoms; System; Testing; Variant; associated symptom; autism spectrum disorder; base; child battery; cognitive process; design; disability; effective therapy; individualized medicine; motor deficit; motor impairment; motor symptom; neuromechanism; operation; relating to nervous system; social; social communication

DESCRIPTION (provided by applicant): While social communication deficits are considered the hallmark of Autism Spectrum Disorders (ASD), there is increasing evidence that sensorimotor deficits are also common in individuals with ASD diagnoses. A large body of research suggests that brain systems for execution and observation of actions are involved in higher social cognitive processes, including intention understanding and empathy, yet research has not yet clarified the extent to which motor deficits, such as imitation ability and motor planning, are central to ASD nor whether social and motor deficits are related neurobiologically in ASD. Understanding the neurobiological basis for ASD is crucial for developing effective therapies. However, researching the neurobiology of ASD is complicated by the heterogeneity of ASD; patients vary in symptomology- e.g., some individuals may show extensive impairment in motor functioning while others may not. Our study is designed to accommodate and understand the relationship between symptomalogical variation in ASD along the dimensions of both social and motor impairments. We aim to show how variations in social and motor symptoms in ASD relate to functioning in social and motor brain networks and functional connectivity between them. We propose to conduct functional MRI studies that compare 120 children on two continua of symptomology: (1) degree of social impairment (as measured by the SRS-2 and NEPSY-II), and (2) degree of motor impairment (as measured by the MABC-2 and Praxis Test). To ensure a range of impairment along these continua, children with ASD and children with Developmental Coordination Disorder (DCD, sometimes called dyspraxia) as well as typically developing (TD) children will participate in the study. The ASD group will range in motor impairment but should show high social impairment, while the DCD group will range in social impairment (generally lower than ASD) but high in motor impairment. Our fMRI tasks are likewise selected to range on a continuum from purely motor tasks to social processing tasks, beginning with motor (hand) execution and imitation tasks and progressing to tasks that incorporate increasing dimensions of social processing (e.g., non-emotional face imitation, emotional face imitation, intention understanding). By testing individuals who represent a continuum of social and motor deficits along a continuum of social and motor tasks we will be able to isolate and understand, in ASD, interactions between: (1) social and sensorimotor symptomologies; (2) activity in social and motor brain networks; and (3) functional connectivity between social and motor brain networks. This understanding will be crucial for developing individualized treatments for ASD. To our knowledge, no fMRI study has examined children with ASD across these multiple continua, nor directly compared them to children with DCD. In addition to contributing to our understanding of ASD, this study will better elucidate the neural mechanisms underlying DCD, which affects 6-13% of school-aged children.

描述（由申请人提供）：虽然社会交流缺陷被认为是自闭症谱系障碍（ASD）的标志，但越来越多的证据表明，在患有ASD诊断的个体中，感觉运动缺陷也很常见。大量研究表明，用于执行和观察行动的大脑系统与更高的社会认知过程有关，包括意图理解和同理心，但研究尚未阐明运动不足（例如模仿能力和运动计划）在ASD中或社会缺陷等运动不足是在ASD中与社会和运动缺陷是否与社会和运动缺陷相关。了解ASD的神经生物学基础对于开发有效的疗法至关重要。但是，研究ASD的神经生物学因ASD的异质性而变得复杂。患者的症状不同 - 例如，某些人可能在运动功能方面表现出广泛的障碍，而另一些人则可能没有。我们的研究旨在适应和了解社会和运动障碍层面ASD的症状变化之间的关系。我们的目的是展示ASD中社会和运动症状的变化与社交和运动脑网络中的功能以及它们之间的功能连通性如何相关。我们建议进行功能性MRI研究，以将120名儿童在两个症状的连续性上进行比较：（1）社会障碍程度（通过SRS-2和NEPSY-II测量），以及（2）运动障碍程度（按MABC-2和PRAXIS测试测量）。为了确保沿这些连续性的一系列损害，患有ASD的儿童和发育协调障碍的儿童（DCD，有时称为dyspraxia）以及通常发育（TD）儿童将参加该研究。 ASD组的运动障碍将范围扩大，但应显示出很大的社会障碍，而DCD组的社会障碍（通常低于ASD），但运动障碍较高。同样，我们的fMRI任务也可以选择从纯粹的电机任务到社交处理任务的连续性范围，从电动机（手）执行和模仿任务开始，然后发展到结合社会处理尺寸增加的任务（例如，非情感面部模仿，情感脸部模仿，意图模仿，意图理解）。通过测试代表社会和运动缺陷连续的社会和运动任务的个人，我们将能够隔离和理解ASD之间的相互作用：（1）社会和感觉运动症状； （2）社交和运动脑网络中的活动； （3）社交和运动脑网络之间的功能连通性。这种理解对于为ASD开发个性化治疗方法至关重要。据我们所知，没有fMRI研究检查了这些多重连续性的ASD儿童，也没有直接将其与DCD儿童进行比较。除了有助于我们对ASD的理解外，这项研究还将更好地阐明DCD的神经机制，这会影响6-13％的学龄儿童。