Atypical Late Neurodevelopment in Autism: A Longitudinal Clinical Phenotype and Multimodal Brain Imaging Study

该项目的目标是确定从儿童时期开始大脑发育的个体差异 与自闭症临床过程和结果的变化有关。我们将在 三步我们将首先从六个月的成像数据中量化个体的整体和区域大脑发育。 使用磁共振成像（体积、皮质厚度、功能）在15年内收集的时间点 连接性、白色物质微观结构）以及同时进行的临床和神经心理学评价。六 时间点将包括我们现有的10年纵向研究（140名男性参与者）的4个时间点 自闭症患者和75名年龄匹配的典型发育参与者），加上在接下来的五年中收集的另外两名 多年来，同一个跨学科的团队。这些扩展队列序列纵向数据将涵盖 3-53岁的我们将在我们广泛的年龄范围内分析年龄-时期-队列效应。更多数据将提供 有足够的把握度来检验个体、队列和组中是否存在线性和曲线发育弧 程度.我们将通过与阅读障碍组的比较来研究自闭症的特异性。二是 确定大脑发育中的中介和调节因素，帮助解释为什么有些人 继续患有严重的自闭症，而其他人则有所改善。第三，我们将分析纵向之间的关联， 脑功能发育和临床结果，通过评估损伤的机制， 范围连接和抑制可能最终影响成人预后。最后，我们将探讨 大脑发育迟缓可能与中学服务的丧失相互作用。我们的发现将阐明 大脑的变化调节核心自闭症症状的严重程度， 紊乱了解大脑后期发育的途径以及大脑成熟与 认知/行为变化对于识别所涉及的生物学机制和理解如何 它们与背景因素相互作用。

The goal of the proposed project is to determine how individual variation in brain development from childhood to adulthood is associated with variation in clinical course and outcome in autism. We will achieve this goal in three steps. We will first quantify individual whole and regional brain development from imaging data across six time points collected over 15 years using magnetic resonance imaging (volume, cortical thickness, functional connectivity, white matter microstructure) and concurrent clinical and neuropsychological evaluations. The six time points will include the four time points from our existing 10-year longitudinal study (140 male participants with autism and 75 age-matched typically developing participants) plus two more collected over the next five years by the same multisite interdisciplinary team. These extended cohort sequential longitudinal data will span 3-53 years of age. We will analyze age-period-cohort effects across our wide age range. More data will provide enough power to test existence of linear and curvilinear developmental arcs at individual, cohort, and group levels. We will investigate the specificity to autism by comparison to a reading disorder group. Second, we will identify mediating and modulating factors within brain development that help explain why some individuals continue to have severe autism while others improve. Third, we will analyze associations between longitudinal brain functional development and clinical outcome by evaluating the mechanism by which impairment in long- range connectivity and inhibition may ultimately impact adult prognosis. Finally, we explore how trajectories of late brain development may interact with the loss of secondary school services. Our findings will elucidate how brain changes modulate the severity of core autism symptoms and in the cognitive profile of individuals with the disorder. Understanding the paths of late brain development and the relation between brain maturation and cognitive/behavioral changes is essential to identify biological mechanisms involved and to understand how they interact with contextual factors.