Cerebellar and Basal Ganglia Markers Underlie Neuromotor Impairments in Adults with Autism Spectrum Disorder (ASD)

小脑和基底神经节标记是成人自闭症谱系障碍 (ASD) 神经运动损伤的基础

• 批准号: 10399614
• 负责人: Zheng Wang
• 金额: $ 38.69万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10399614
• 关键词: Acceleration; Adult; Age; Aging; Anatomy; Anisotropy; Area; Axon; Basal Ganglia; Behavioral; Biomechanics; Biometry; Brain; Cell Nucleus; Cerebellar Diseases; Cerebellar degeneration; Cerebellum; Child; Clinical; Clinical assessments; Data; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Equilibrium; Fingers; Foundations; Functional Imaging; Functional Magnetic Resonance Imaging; General Population; Globus Pallidus; Goals; Hip region structure; Impairment; Infant; Intervention; Knowledge; Lateral; Lobule; Magnetic Resonance Imaging; Measures; Mission; Monitor; Motor; Movement; Movement Disorders; Musculoskeletal Equilibrium; Nerve Degeneration; Neurodegenerative Disorders; Neurodevelopmental Disorder; Parietal Lobe; Parkinsonian Disorders; Patients; Performance; Physics; Postural adjustments; Posture; Prevalence; Process; Production; Quality of life; Reporting; Research; Research Personnel; Severities; Substantia nigra structure; Testing; Time; Tissues; Transportation; Water; Work; adolescent with autism spectrum disorder; adult with autism spectrum disorder; aged; autism spectrum disorder; autistic children; balance testing; base; biobehavior; comorbidity; design; experience; extracellular; grasp; gray matter; high reward; imaging approach; imaging study; innovation; insight; motor deficit; neurophysiology; putamen; sex; trait; water diffusion; white matter

PROJECT SUMMARY/ABSTRACT Although conceptualized as a neurodevelopmental disorder with present research primarily focused on infants and children, autism spectrum disorder (ASD) has increasingly been recognized as a lifelong condition with the potential to have a detrimental impact on adult functioning and quality of life. Based on clinical observations that mid-to-older aged adults with ASD may be particularly susceptible to neurodegenerative diseases during aging, the proposed studies will test the central hypothesis that the cerebellum and basal ganglia are selectively disrupted in adults with ASD aged 40 to 60 years. And, this disruption is associated with neuromotor impairments and clinical signs of movement disorders. Free-water diffusion magnetic resonance imaging (FWdMRI) will be applied to quantify neuronal degeneration of the cerebellar lobules, dentate, and basal ganglia nuclei and axonal integrity of cerebellar peduncles to determine whether these subcortical targets are disrupted in adults with ASD relative to age-, sex-, and IQ-matched controls. Functional MRI (fMRI) of precision grip will be used to quantify abnormal activations of cortico-subcortical brain targets and whether these alterations underpin grip force production-related impairments in ASD. Using neuromotor tests sensitive in detecting alterations of the cerebellum and basal ganglia, we will clarify the extent to which performance of Romberg stances, quick step initiation, sit-to-stance balance, and goal-directed finger-pointing is compromised in adults with ASD. Guided by strong preliminary data, we will pursue three specific aims: Aim 1) Determine structural alterations in the cerebellum and basal ganglia in adults with ASD using FWdMRI. Aim 2) Determine functional deficits in the cerebellum and basal ganglia in adults with ASD using motor fMRI. Aim 3) Determine neuromotor impairments in adults with ASD. Our group is uniquely qualified to undertake this critical R01 project as it includes investigators with expertise and experience in sensorimotor neurophysiology in ASD, ASD diagnosis, aging and movement disorders, MRI physics and research, and biostatistics. This proposal is scientifically innovative as it will be the first to systematically quantify aging-related neuromotor issues in ASD at the levels of brain, behavioral, and clinical domains. This project is significant as it holds the promise to identify putative non-invasive traits of subcortical brain targets contributing to aging in ASD. If successful, this work will identify new brain and biobehavioral targets that can be tracked to understand, monitor, and treat aging-related conditions in ASD.

项目摘要/摘要 尽管被概念化为一种神经发育障碍，目前的研究主要集中于婴儿 和儿童，自闭症谱系障碍（ASD）越来越被认为是终身状况 对成人功能和生活质量产生不利影响的潜力。基于临床观察 患有ASD的中年龄成年人可能特别容易受到衰老期间神经退行性疾病的影响， 拟议的研究将检验中心假设，即小脑和基底神经节是有选择的 在40至60岁的ASD成年人中受到破坏。而且，这种干扰与神经运动障碍有关 和运动障碍的临床体征。自由水扩散磁共振成像（FWDMRI）将是 用于量化小脑小叶，齿状和基底神经节核和轴突的神经元变性 小脑子花序的完整性，以确定在ASD的成年人中这些皮质下靶标是否破坏 相对于年龄，性别和智商匹配的对照。精度握把的功能性MRI（fMRI）将用于量化 皮质增生的大脑靶标的异常激活以及这些改变是否支撑力 与生产有关的ASD损伤。使用神经运动测试敏感检测 小脑和基底神经节，我们将阐明Romberg立场表现的程度，快速步骤 在患有ASD的成年人中，启动，静坐平衡和目标指导的指导是损害的。指导 强大的初步数据，我们将追求三个具体目标：目标1）确定结构性改变 使用FWDMRI的ASD成年人的小脑和基底神经节。目标2）确定功能缺陷 使用电动机fMRI的ASD成年人的小脑和基底神经节。目标3）确定神经运动障碍 在ASD的成年人中。我们的小组具有独特的资格进行此关键R01项目，因为它包括调查人员 具有ASD的ASD诊断，衰老和运动的感觉运动神经生理学方面的专业知识和经验 疾病，MRI物理和研究以及生物统计学。该建议在科学上是创新的，因为它将是 首先是在大脑，行为和 临床领域。该项目很重要，因为它具有确定假定的非侵入性特征的承诺 皮层脑靶标有助于ASD衰老。如果成功，这项工作将确定新的大脑， 可以跟踪以理解，监测和治疗与衰老相关的疾病的生物行为靶标。