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.

拟议项目的目的是确定从小脑发育的个体变异 成年与自闭症的临床病程和结果的差异有关。我们将实现这一目标 三个步骤。我们将首先从六个的成像数据中量化整体和区域大脑的发展 使用磁共振成像（体积，皮质厚度，功能性）收集了15年内的时间点 连通性，白质微观结构）以及并发临床和神经心理学评估。六个 时间点将包括我们现有10年纵向研究的四个时间点（140名男性参与者 自闭症和75个年龄匹配的通常是发展参与者）以及在接下来的五个 同一多站点跨学科团队的年份。这些扩展的队列顺序纵向数据将跨越 3-53岁。我们将分析在我们广泛的年龄范围内的年龄 - 周期性效果。更多数据将提供 足够的能力来测试单个，队列和组的线性和曲线发育弧的存在 水平。通过与阅读障碍组相比，我们将研究对自闭症的特异性。第二，我们会的 确定大脑发育中的中介和调节因素，以帮助解释为什么某些人 继续患有严重的自闭症，而其他人则改善。第三，我们将分析纵向之间的关联 通过评估长期损害的机制，大脑功能发育和临床结果 范围连通性和抑制作用最终可能会影响成人预后。最后，我们探讨了如何 晚期大脑发育可能与中学服务的丧失相互作用。我们的发现将阐明如何 大脑变化调节核心自闭症症状的严重程度以及 疾病。了解晚期大脑发育的路径以及大脑成熟与 认知/行为改变对于识别涉及的生物学机制并了解如何 他们与上下文因素互动。