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

自闭症的非典型晚期神经发育：纵向临床表型和多模态脑成像研究

• 批准号: 9196935
• 负责人: JANET Elizabeth LAINHART
• 金额: $ 77.2万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9196935
• 关键词: Adolescence; Adult; Affect; Age; Age-Years; Autistic Disorder; Automobile Driving; Behavioral; Biological; Brain; Brain imaging; Childhood; Clinical; Cognitive; Cohort Effect; Data; Development; Disease; Evaluation; Functional Magnetic Resonance Imaging; Future; Goals; Growth; Image; Impairment; Individual; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Mediating; Neurocognitive; Outcome; Participant; Play; Preventive Intervention; Reading Disorder; Research; Role; Sampling; Secondary Schools; Services; Severities; Specificity; Structure; Subgroup; Symptoms; Testing; Thick; Time; Variant; associated symptom; clinical phenotype; clinically relevant; cohort; contextual factors; daily functioning; gray matter; improved; improved outcome; indexing; insight; intervention effect; male; neurodevelopment; neuropsychological; outcome forecast; white matter; young adult

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.

该项目的目标是确定儿童时期大脑发育的个体差异。 成年期与自闭症的临床病程和结局的变化有关。我们将在#年实现这一目标。 三个步骤。我们将首先从六个人的成像数据中量化个人、整个和区域大脑的发展 使用磁共振成像收集超过15年的时间点(体积、皮质厚度、功能 连接性、脑白质微结构)以及同时进行的临床和神经心理学评估。六人组 时间点将包括我们现有的10年纵向研究(140名男性参与者)中的四个时间点 患有自闭症和75名年龄匹配的典型发展中参与者)，外加在接下来的五年中收集的另外两名 多年来，同一个多地点跨学科团队。这些扩展队列序列纵向数据将跨越 3-53岁。我们将分析我们广泛的年龄范围内的年龄-时期-队列效应。更多数据将提供 足够的力量来测试个人、队列和群体是否存在线性和曲线发展弧线 级别。我们将通过与阅读障碍组进行比较来研究自闭症的特异性。第二，我们将 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，而其他人的病情有所改善。第三，我们将分析纵向关系 通过评估脑功能发育和临床预后的机制来评估长期和长期的脑功能损害。 射程连接和抑制最终可能影响成人的预后。最后，我们探讨了轨道是如何 大脑发育迟缓可能与中学教育服务的丧失相互作用。我们的发现将阐明 大脑的变化调整了自闭症核心症状的严重程度，并影响了患有自闭症的个人的认知特征 这是一种混乱。了解脑发育晚期的途径以及脑成熟与脑发育的关系 认知/行为变化对于确定相关的生物机制和理解 它们与背景因素相互作用。