Intrinsic Brain Architecture of Young Children with Autism While Awake and Asleep

自闭症幼儿清醒和睡眠时的内在大脑结构

• 批准号: 8621724
• 负责人: Adriana Di Martino
• 金额: $ 25.43万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-05 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8621724
• 关键词: Address; Adult; Age; Architecture; Atlases; Autistic Disorder; Biological Markers; Brain; Brain imaging; Brain region; Child; Communities; Confidentiality; Corpus striatum structure; Data; Data Set; Development; Electroencephalography; Exploratory/Developmental Grant; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Image Analysis; Individual Differences; Infant; Lead; Literature; Maps; Measures; Mental disorders; Methods; National Institute of Mental Health; Participant; Pattern; Population; Process; Property; Psychopathology; Reporting; Research Design; Rest; Sampling; Scanning; School-Age Population; Science; Scientist; Severities; Sleep; Sleep Stages; Surveys; Syndrome; System; Testing; Wakefulness; Work; autism spectrum disorder; awake; brain behavior; data sharing; early onset; emerging adult; falls; imaging modality; indexing; neuroimaging; prospective; public health relevance; trait

Abstract Functional neuroimaging is increasingly enhancing our understanding of autism spectrum disorders (ASD) as disconnection syndromes, but because of its demands, most studies have focused on adults or older children. Conducting functional neuroimaging during natural sleep permits the study of young children and infants. Given the early onset of ASD, such studies may be crucial to the identification of biomarkers. However, the assumption that findings obtained during sleep can be generalized to wakefulness has not yet been systematically tested. This exploratory proposal represents a first step to fill this important gap by studying young children with ASD in two conditions - wakefulness and natural sleep - using resting-state functional magnetic resonance imaging (R-fMRI). By quantifying intrinsic functional connectivity (iFC) throughout the brain, R-fMRI provides a wealth of information about functional brain circuitry. While differences between asleep and awake R-fMRI in healthy adults have been described, to date, iFC measures in sleeping young children with ASD have not been systematically characterized, nor have they been contrasted with wakefulness. Accordingly, our overarching goal is to provide an initial systematic characterization of the stability (reliability) across states (awake and sleep) of whole-brain iFC in children with ASD. We propose to collect R-fMRI while awake and during natural sleep in at least 20 children with ASD between the ages of 66 to 90 months - starting at the youngest ages at which children can be successfully scanned while awake. We will survey whole brain iFC employing structural and functional parcellation units commonly examined in the literature. We will also compute other whole-brain voxel-wise measures of intrinsic brain functional architecture previously reported to be abnormal in ASD and which capture specific properties not otherwise characterized by traditional correlation analyses. These include Voxel Mirrored Homotopic Connectivity, Regional Homogeneity, Fractional Amplitude of Low Frequency Fluctuations, Degree Centrality and Independent Component Analyses. Our hypothesis generating aims are (1) to test for significant differences between wakefulness and sleep across children with ASD, and (2) to systematically characterize the stability (reliability) of between-individual differences in R-fMRI measures across states (asleep, awake) as indexed by intraclass correlation coefficients. We will also address additional questions regarding the effects of different parcellation systems on measures of stability, the stability of brain-behavior relationships with ASD measures, and derive initial estimates of within-session test-retest reliability. Finally, to maximize the impact of this effort, we will make fully anonymized data available to the scientific community every six months as the data are collected. We expect such prospective data sharing to further enhance the scientific value of the proposed efforts. This will accelerate the pace at which the collected data can be used as a foundation for future efforts to study increasingly younger children so as to delineate the underlying pathophysiology of ASD.

抽象的 功能性神经影像越来越多地增强了我们对自闭症谱系障碍（ASD）的理解 断开连接综合征，但由于其要求，大多数研究都集中在成年人或年龄较大的儿童上。 自然睡眠期间进行功能性神经成像允许研究幼儿和婴儿。 鉴于ASD的早期发作，此类研究可能对生物标志物的识别至关重要。但是， 假设睡眠期间获得的发现可以推广到清醒 系统测试。该探索性提案是通过研究来填补这一重要空白的第一步 在两个条件下ASD患有ASD的幼儿 - 清醒和自然睡眠 - 使用静止状态功能 磁共振成像（R-FMRI）。通过量化整个固有的功能连接（IFC） 大脑，R-FMRI提供了有关功能性脑电路的大量信息。而之间的差异 迄今为止，在健康成年人中，已经描述了IFC的年轻人量度 患有ASD的儿童尚未系统地表征，也没有与 清醒。因此，我们的总体目标是提供对该的初始系统表征 ASD儿童的全脑IFC跨州（清醒和睡眠）的稳定性（可靠性）。我们建议 在醒着和自然睡眠中收集R-FMRI至少20名ASD的儿童，年龄在66岁之间 90个月 - 从最年轻的年龄开始，可以在醒着时成功扫描儿童。我们将 调查整个大脑IFC，采用常见于 文学。我们还将计算内在大脑功能架构的其他全脑素体衡量 先前据报道在ASD中是异常的，并且捕获特定特性未表征 通过传统的相关分析。这些包括素镜同型连接性，区域性连接 同质性，低频波动的分数幅度，程度中心性和独立 组件分析。我们的假设产生目标是（1）测试 ASD儿童的清醒和睡眠，（2）系统地表征稳定性（可靠性） 跨州的R-FMRI措施的个体间差异（入睡，清醒），如类插入 相关系数。我们还将解决有关不同分割影响的其他问题 稳定度量的系统，脑行为与ASD度量的稳定性，并得出 会议内测试可靠性的初步估计。最后，为了最大化这项工作的影响，我们将 收集数据时，每六个月向科学界提供一次完全匿名的数据。 我们希望这种潜在的数据共享能够进一步增强拟议工作的科学价值。这 将加速收集数据的速度，以此作为未来研究的基础 越来越年轻的孩子描绘了ASD的基本病理生理学。