Electrophysiological Signatures of Language Impairment in Autism Spectrum Disorde

描述（由申请人提供）：几种发育障碍的临床特征，包括自闭症谱系障碍（ASD），涉及不同程度的共病语言障碍（LI）。然而，考虑到LI的异质性，临床诊断本身并不能识别相关的潜在神经元缺陷，这些缺陷可能发生在感知、加工和/或认知水平。目前对这些水平的缺陷如何与LI相关的理解还不够复杂，无法区分基于神经元的LI亚型。这样的分类一方面可以再现现有的临床分类，另一方面，也可以跨越临床诊断，根据潜在的神经元缺陷的性质将语言障碍患者分组。该研究计划的成功实施将代表着通过对年轻临床人群与正常发展的同龄人在言语感知、加工和认知过程中诱发的神经磁活动的参数调查来确定LI亚型的进展。具体来说，研究人员将对患有自闭症谱系障碍的儿童（包括伴有和不伴有LI的儿童）进行调查，以发现与自闭症本身和LI本身以及两者相关联的神经元特征。因此，本提案的目标是定义与ASD中LI的神经相关因素相关的电生理特征或内表型，以解决ASD诊断中跨谱行为障碍的异质性（“异质性”问题）和不同诊断之间行为障碍的明显重叠（“重叠”问题）。

DESCRIPTION (provided by applicant): The clinical profiles of several developmental disorders, including autism spectrum disorders (ASD), involve varying degrees of comorbid language impairment (LI). Clinical diagnosis of LI, however, does not itself identify the associated underlying neuronal deficit(s), which may occur at the level of perception, processing, and/or cognition, given the observed heterogeneity of LI. Current understanding of how a deficit at each or any of these levels might relate to LI is not sufficiently sophisticated to distinguish neuronally-based subtypes of LI. Such classification may, on the one hand, reproduce existing clinical categories, or, on the other hand, cut across clinical diagnoses and instead group together language impaired individuals by the nature of their underlying neuronal deficit. Successful implementation of the proposed research program will represent progress towards delineating subtypes of LI identified via parametric investigation of evoked neuromagnetic activity during speech perception, processing, and cognition in young clinical populations vs. typically developing peers. Specifically a population of children with autism spectrum disorders (both with and without concomitant LI) will be investigated to find neuronal characteristics associated with both autism per se and LI per se, as well as in combination. As such, it is the goal of this proposal to define electrophysiological signatures, or endophenotypes, associated with the neural correlates of LI in ASD to address both the heterogeneity of the behavioral impairment across the spectrum within the diagnosis of ASD (the "heterogeneity" problem) and the apparent overlap in behavioral impairment between different diagnoses (the "overlap" problem).