Phase-Amplitude Coupling and Dysfunction in ASD

摘要：这项建议研究了局部皮质-皮质连接如何形成脑出血的生物学基础 自闭症谱系障碍(ASD)。ASD在我们的社会中的发病率约为1%，但 ASD的特征是没有已知的单一病因，或者实际上是表型。的不足之处 在ASD患者中反复观察到远程脑连接，特别是在丘脑皮质 以及与听觉和相关语言系统相关联的联想投影。然而，最近 研究表明，ASD患者的局部皮质-皮质连接也可能被破坏。本地 相位幅度耦合(PAC)是一种静止状态的大脑皮层机制，通过它 低频皮层振荡选通或调制高频振荡，如伽马- 乐队活动。PAC已在多个大脑区域被观察到，并被认为是一种常见的 用于神经元组件之间的定时通信的机械框架，从而提供了一种 可测量的局部功能连通性分析。PAC可以用以下方法测量 脑磁图(MEG)，不依赖于基于任务的试验。该提案使用PAC来 通过首先验证PAC是一种敏感的方法来克服基于任务的MEG的实验低效 ASD中的静息状态指标，然后将局部PAC的测量扩展到整个大脑。AIM 1使用 以听觉系统为测试平台表征静息状态下颞叶优势的贡献 脑回PAC与先前描述的发育异常和信号传导延迟有关。目标 2将PAC扩展为整个大脑的对比图，并阐明了大脑皮质的空间模式 ASD中的功能障碍。目的3使用弥散磁共振将白质结构与PAC相关联。我们 假设结构连通性和PAC之间的空间关联模式将是 在ASD中降解。 为了实现这些目标，我们将比较学龄儿童(6-15岁)之间的PAC 患有自闭症和典型发育障碍的儿童。这项建议充分利用了现有的一大批人 已经包括53名ASD儿童(平均年龄10.4±2.4岁)和39名对照儿童(平均年龄 11.0±2.7岁)，他们接受了神经心理测试、脑磁图和磁共振成像，数据可评估 所有域。这项多式联运方案的创新之处在于，验证PAC作为 局部连通性的敏感度量和用于将PAC扩展为可泛化的方法 ASD患者整个大脑皮质-皮质连接性的测量。这项调查将提供新的 对结构-功能关系如何在整个大脑中发展的洞察，以及信息 当代理论认为自闭症是一种连通性障碍。

Abstract: This proposal examines how local cortico-cortical connectivity forms a biological basis of autism spectrum disorder (ASD). The incidence of ASD in our society is about 1% but characteristically there is no known singular etiology, or indeed phenotype, of ASD. Deficiencies in long-range brain connectivity have been repeatedly observed in ASD, especially in thalamocortical and association projections associated with auditory and related language systems. However, recent studies have indicated that local cortico-cortical connections may also be disrupted in ASD. Local phase amplitude coupling (PAC) has emerged as a resting-state cortico-cortical mechanism by which low-frequency cortical oscillations gate or modulate higher frequency oscillations such as gamma- band activity. PAC has been observed in multiple brain regions and is thought to be a common mechanistic framework for timing communication between neuronal assemblies, and thus provides a measureable assay of local functional connectivity. PAC can be measured with magnetoencephalography (MEG) and does not rely on task-based trials. This proposal uses PAC to overcome the experimental inefficiencies of task-based MEG by first validating PAC as a sensitive resting-state metric in ASD and then extending measures of local PAC across the brain. Aim 1 uses the auditory system as a testbed to characterize the contribution of resting-state superior temporal gyrus PAC to previously described developmental irregularities and delays in signal conduction. Aim 2 extends PAC as a contrast map across the brain and elucidates spatial patterns of cortical dysfunction in ASD. Aim 3 uses diffusion MR to correlate white matter structure to PAC. We hypothesize that the spatial correlation pattern between structural connectivity and PAC will be degraded in ASD. To accomplish these goals, we will contrast PAC between groups of school-aged (6-15yrs) children with ASD and typically-developing controls. This proposal leverages a large existing cohort which already consists of 53 ASD (mean age 10.4±2.4yrs) and 39 control children (mean age 11.0±2.7yrs) who underwent neuropsychological testing, MEG, and MRI with evaluable data across all domains. This multimodal proposal is innovative in both the concept of validating PAC as a sensitive metric of local connectivity and the methods used to extend PAC as a generalizable measure of cortico-cortical connectivity across the brain in ASD. This investigation will provide new insights into how the structure-function relationship develops across the brain, as well informing contemporary theories of ASD as a disorder of connectivity.