Phase-Amplitude Coupling and Dysfunction in ASD

ASD 中的相幅耦合和功能障碍

• 批准号: 9317752
• 负责人: JEFFREY I BERMAN
• 金额: $ 25.8万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9317752
• 关键词: Address; Age; Auditory; Auditory Evoked Potentials; Auditory area; Auditory system; Behavioral; Biological; Biological Assay; Brain; Brain region; Cerebral cortex; Cerebrum; Characteristics; Child; Clinical; Communication; Communication impairment; Coupled; Coupling; Data; Development; Diffusion; Disease; Electrophysiology (science); Etiology; Evaluable Disease; Frequencies; Functional disorder; Goals; Heterogeneity; High Frequency Oscillation; High Prevalence; Incidence; Income; Investigation; Laboratories; Language; Language Disorders; Magnetic Resonance Imaging; Magnetoencephalography; Maps; Measures; Methods; Neuronal Dysfunction; Neurons; Neuropsychological Tests; Parietal; Pathology; Pathway interactions; Pattern; Phase; Phenotype; Play; Process; Property; Readiness; Rest; Role; School-Age Population; Sensory; Signal Transduction; Societies; Structure; Structure-Activity Relationship; Superior temporal gyrus; Symptoms; System; Work; auditory pathway; autism spectrum disorder; base; cognitive ability; cohort; disorder control; experimental study; fusiform face area; indexing; innovation; insight; interest; multimodality; novel; response; sensory signal detection; source localization; theories; white matter

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.

翻译后摘要：本提案探讨如何局部皮质-皮质连接形成的生物学基础， 自闭症谱系障碍（ASD）。ASD在我们社会中的发病率约为1%， 特征性地，ASD没有已知的单一病因或实际上的表型。缺陷 在ASD中反复观察到长距离脑连接，特别是在丘脑皮质 以及与听觉和相关语言系统相关的联想投射。但最近的 研究表明，在ASD中，局部皮质-皮质连接也可能被破坏。当地 相位振幅耦合（PAC）已经作为静息态皮质-皮质机制出现， 低频皮层振荡选通或调制高频振荡， 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 神经元组件之间的定时通信的机制框架，并因此提供了一个 局部功能连接性的可测量测定。PAC可以用 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作为一种敏感的 ASD中的静息状态度量，然后将局部PAC的测量扩展到整个大脑。Aim 1使用 听觉系统作为表征静息态上级颞叶 PAC回与先前描述的发育不规则和信号传导延迟有关。目的 2扩展PAC作为整个大脑的对比图，并阐明皮质的空间模式 ASD的功能障碍目的3利用扩散磁共振将白色物质结构与PAC相关联。我们 假设结构连通性和PAC之间的空间相关模式将是 在ASD中退化。 为了实现这些目标，我们将比较学龄组（6- 15岁）之间的PAC 自闭症儿童和正常发育的对照组。该提案利用了大量现有的队列 其中ASD组53例（平均年龄10.4± 2.4岁），对照组39例（平均年龄10.4± 2.4岁 11.0± 2.7岁），接受神经心理学测试、MEG和MRI， 所有域。这种多式联运的建议是创新的概念，验证PAC作为一个 局部连通性的敏感度量和用于将PAC扩展为可推广的 测量ASD患者大脑中的皮质-皮质连接。这项调查将提供新的 深入了解大脑的结构-功能关系是如何发展的， ASD是一种连接障碍的现代理论。