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.

摘要 功能性神经影像学越来越多地增强了我们对自闭症谱系障碍（ASD）的理解， 断连综合征，但由于它的要求，大多数研究都集中在成人或年龄较大的儿童。 在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的早期发病，这些研究可能对生物标志物的鉴定至关重要。但 假设在睡眠中获得的发现可以推广到清醒状态， 系统测试。这一探索性建议是填补这一重要空白的第一步， ASD幼儿在两种情况下-清醒和自然睡眠-使用静息状态功能 磁共振成像（R-fMRI）。通过量化整个系统的内在功能连接性（iFC）， R-fMRI提供了丰富的关于功能性脑回路的信息。虽然差异 健康成人的睡眠和清醒R-fMRI已经被描述，到目前为止，睡眠中的年轻人的iFC测量 ASD儿童尚未被系统地描述，也没有与 清醒因此，我们的首要目标是提供一个初步的系统表征， ASD儿童全脑iFC在不同状态（清醒和睡眠）下的稳定性（可靠性）我们建议 收集至少20名年龄在66岁至69岁之间的ASD儿童清醒和自然睡眠时的R-fMRI。 90个月-从最小的年龄开始，儿童可以在清醒时成功扫描。我们将 使用在研究中通常检查的结构和功能分组单元调查全脑iFC 文学我们还将计算其他全脑体素的内在脑功能结构的措施 先前报道在ASD中是异常的，并且其捕获了未以其他方式表征的特定性质 传统的相关分析。这些包括体素镜像同伦连接，区域 低频波动的齐次性、分数振幅、度中心性和独立性 成分分析。我们的假设产生的目的是（1）测试之间的显着差异 ASD儿童的觉醒和睡眠，以及（2）系统地表征稳定性（可靠性） 不同状态（睡眠，清醒）下R-fMRI测量的个体间差异， 相关系数我们还将讨论有关不同分割效果的其他问题 系统的稳定性措施，稳定的大脑行为关系与ASD措施，并得出 期内重测信度的初步估计。最后，为了最大限度地发挥这一努力的影响，我们将 在收集数据时，每六个月向科学界提供完全匿名的数据。 我们期望这种前瞻性的数据共享将进一步提高拟议努力的科学价值。这 将加快收集的数据可用作未来研究工作基础的步伐 越来越年轻的儿童，以便描绘ASD的潜在病理生理学。