An fMRI investigation of propagated intrinsic activity in early development and autism

描述（由申请人提供）：自闭症谱系障碍（ASD）是一组异质性神经发育障碍，其特征是社交功能受损、重复行为和兴趣范围有限。ASD大约每88人中就有1人受到影响，而且发病率似乎在上升。在ASD中，适应功能、认知和语言能力以及神经系统共病存在广泛的表型异质性，导致许多人将这些各种疾病称为“自闭症”。因此，出现了两个关键问题：（1）尽管存在表型和遗传异质性，但ASD是否具有共同的神经生物学特征？(2)这种神经生物学特征可以在人体内进行研究吗？这些问题的答案将代表我们对ASD的理解以及我们诊断和治疗这种疾病的能力向前迈出了重要的一步。我们最近开发了一种新的技术，用于分析静息状态的功能磁共振成像数据的基础上映射传播的内在大脑活动。当应用于高功能成人ASD的fMRI数据时，新方法在检测局灶性脑异常方面似乎比传统的功能连接分析更敏感。该项目的目标是将这种新技术应用于在年轻的，通常发育中的儿童以及患有ASD的儿童中收集的fMRI数据。初步结果表明，我们的方法检测的变化，在组水平上，在6个月大的儿童，随后发展临床ASD的内在活动的时间结构。这一发现与最近的尸检病理学证据相一致，即ASD患者在生命早期（甚至可能在子宫内）的皮质组织被破坏。内在活动的时间结构、神经元可塑性和早期脑发育之间的密切关系为这项研究提供了强有力的理论基础。具体的研究问题包括：（1）ASD儿童的传播性内在活动模式在群体水平上与正常发育儿童不同的最早年龄是多少？(2)不同年龄的ASD是否会影响不同的大脑区域？这些问题的答案可能会阐明ASD的神经生物学基础。通过调查ASD的原因和发展轨迹，我们的项目直接符合NIMH战略计划的前两个目标。我们阿索将探讨在典型的早期发育过程中，传播的内在活动模式是如何变化的，以更好地理解正常发育里程碑的神经相关性。正常发育的特征可以为其他神经发育障碍的未来研究提供信息。

DESCRIPTION (provided by applicant): Autism spectrum disorders (ASD) constitute a heterogeneous group of neurodevelopmental disorders characterized by impaired social-communication function, repetitive behaviors, and a restricted range of interests. ASD affects approximately 1 in every 88 individuals and the incidence appears to be rising. Within ASD, there exists wide phenotypic heterogeneity in adaptive function, cognitive and language abilities, and neurological comorbidities, leading many to refer to these various disorders as 'the autisms'. Therefore, two key questions emerge: (1) Despite phenotypic and genetic heterogeneity, does ASD have common neurobiological signatures? (2) Can such neurobiological signatures be studied in vivo in humans? Answers to these questions would represent a significant step forward in our understanding of ASD, as well as our ability to diagnose and treat this condition. We have recently developed a new technique for the analysis of resting state fMRI data based on mapping propagated intrinsic brain activity. When applied to fMRI data obtained in high-functioning adults with ASD, the new method appears to be more sensitive than conventional functional connectivity analysis in detecting focal brain abnormalities. The objective of this project is to apply this new technique to fMRI data collected in young, typically developing children, as well as children who develop ASD. Preliminary results indicate that our method detects changes, at the group level, in the temporal structure of intrinsic activity in 6-month-old children who subsequently develop clinical ASD. This finding is consistent with recent post-mortem pathology evidence of disrupted cortical organization in individuals with ASD very early in life, perhaps even in utero. The intimate relationships between the temporal structure of intrinsic activity, neuronal plasticity, and early brain development provide a strong theoretical basis for this investigation. Specific questions to be investigated include: (1) what is the earliest age at which patterns of propagated intrinsic activity in childre with ASD differ, at the group level, from typically developing children? (2) Are different brain regions affected by ASD at different ages? Answers to these questions may illuminate the neurobiological basis of ASD. By investigating the causes and developmental trajectory of ASD, our project is directly in line with the first two objectives of the NIMH strategic plan. We will aso explore how patterns of propagated intrinsic activity change over the course of typical early development to gain a better understanding of the neural correlates of normal developmental milestones. Characterization of normal development could inform future investigations of other neurodevelopmental disorders.