The neurobiological basis of heterogeneous social and motor deficits in ASD

描述（由申请人提供）：虽然社会沟通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，感觉运动缺陷在ASD患者中也很常见。大量研究表明，执行和观察行动的大脑系统参与了包括意图理解和共情在内的高级社会认知过程，但研究尚未阐明运动缺陷（如模仿能力和运动计划）在ASD中的核心程度，也未阐明社交和运动缺陷在ASD中是否存在神经生物学上的相关性。了解自闭症谱系障碍的神经生物学基础对于开发有效的治疗方法至关重要。然而，ASD的神经生物学研究因其异质性而变得复杂；患者的症状各不相同，例如，一些人可能表现出广泛的运动功能损伤，而另一些人可能没有。我们的研究旨在适应和理解自闭症谱系障碍在社交和运动障碍方面的症状变异之间的关系。我们的目标是展示自闭症患者社交和运动症状的变化如何与社交和运动脑网络的功能以及它们之间的功能连接联系起来。我们建议进行功能性MRI研究，比较120名儿童的两种症状连续性：(1)社交障碍程度（由SRS-2和NEPSY-II测量）和(2)运动障碍程度（由MABC-2和Praxis测试测量）。为了确保这些持续的损害范围，患有ASD的儿童和患有发育协调障碍（DCD，有时称为运动障碍）的儿童以及典型发育（TD）儿童将参与这项研究。ASD组有运动障碍，但社交障碍程度高；DCD组有社交障碍（一般低于ASD），但运动障碍程度高。同样，我们的fMRI任务也被选择在一个连续的范围内，从纯粹的运动任务到社会处理任务，从运动（手）执行和模仿任务开始，发展到包含越来越多社会处理维度的任务（例如，非情绪面部模仿，情绪面部模仿，意图理解）。通过测试那些在社会和运动任务中表现出连续的社会和运动缺陷的个体，我们将能够在ASD中隔离和理解以下之间的相互作用：(1)社会和感觉运动症状；(2)社会和运动脑网络的活动；(3)社交和运动脑网络之间的功能连接。这一认识对于开发ASD的个体化治疗方法至关重要。据我们所知，目前还没有功能性磁共振成像（fMRI）研究对ASD患儿进行过这些多重连续体的检查，也没有将其与DCD患儿进行过直接比较。除了有助于我们对ASD的理解外，本研究还将更好地阐明影响6-13%学龄儿童的DCD的神经机制。

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.