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诊断的个体中也很常见。大量的研究表明，大脑系统的执行和观察的行动参与了更高的社会认知过程，包括意图理解和同情，但研究尚未澄清的程度，运动缺陷，如模仿能力和运动规划，是中央ASD，也没有社会和运动缺陷相关的神经生物学在ASD。了解ASD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，研究ASD的神经生物学由于ASD的异质性而变得复杂;患者在神经生物学方面各不相同-例如，有些人可能在运动功能方面表现出广泛的损伤，而另一些人则可能没有。我们的研究旨在适应和理解ASD沿着社会和运动障碍维度的神经学变化之间的关系。我们的目标是展示ASD中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有关。我们建议进行功能性MRI研究，比较120名儿童的两个连续体：（1）社会障碍程度（由SRS-2和NEPSY-II测量），（2）运动障碍程度（由MABC-2和Praxis测试测量）。为了确保这些连续体的一系列损伤沿着，ASD儿童和发育协调障碍（DCD，有时称为运动障碍）儿童以及典型发育（TD）儿童将参与研究。ASD组将在运动障碍范围内，但应显示出高度的社会障碍，而DCD组将在社会障碍范围内（通常低于ASD），但运动障碍程度较高。我们的功能磁共振成像任务同样被选择为从纯粹的运动任务到社会处理任务的连续体，从运动（手）执行和模仿任务开始，并逐渐发展到包括社会处理的增加维度的任务（例如，非情绪面部模仿、情绪面部模仿、意图理解）。通过测试那些代表连续的社会和运动缺陷的个体，沿着连续的社会和运动任务，我们将能够分离和理解ASD中以下因素之间的相互作用：（1）社会和感觉运动神经系统;（2）社会和运动脑网络中的活动;（3）社会和运动脑网络之间的功能连接。这种理解对于开发ASD的个性化治疗至关重要。据我们所知，没有fMRI研究在这些多连续体中检查ASD儿童，也没有直接将他们与DCD儿童进行比较。除了有助于我们理解ASD之外，这项研究还将更好地阐明DCD的神经机制，DCD影响6-13%的学龄儿童。

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.