Cerebellar and basal ganglia contributions to neuromotor decline in adults with autism spectrum disorder (ASD)

小脑和基底神经节对自闭症谱系障碍 (ASD) 成人神经运动衰退的影响

• 批准号: 10056961
• 负责人: Zheng Wang
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056961
• 关键词: Acceleration; Adult; Age; Aging; Anatomy; Anisotropy; Anterior; Axon; Basal Ganglia; Behavior; Behavioral; Biomechanics; Biometry; Brain; Cell Nucleus; Cerebellar Ataxia; Cerebellar Diseases; Cerebellum; Child; Clinical; Clinical assessments; Data Collection; Deterioration; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Elderly; Equilibrium; Fingers; Foundations; Functional Imaging; Functional Magnetic Resonance Imaging; Future; Goals; Hip region structure; Image; Impairment; Individual; Infant; Inferior; Intervention; Knowledge; Laboratories; Lateral; Lobule; Magnetic Resonance Imaging; Measures; Mission; Monitor; Motor; Motor Ataxias; Movement; Movement Disorders; Musculoskeletal Equilibrium; Nerve Degeneration; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurologic; Neurons; Parkinsonian Disorders; Patients; Performance; Physics; Population; Postural adjustments; Prevalence; Process; Quality of life; Reporting; Research; Research Personnel; Severities; Spinal Cord; Structure; Substantia nigra structure; Symptoms; Testing; Time; Transportation; Water; Work; aged; autism spectrum disorder; autistic children; balance testing; base; biobehavior; cognitive ability; comorbidity; density; experience; extracellular; grasp; gray matter; high reward; high risk; imaging study; innovation; insight; neurophysiology; putamen; recruit; relating to nervous system; sex; success; 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. Point 1: Based on preliminary findings that individuals with ASD may be particularly susceptible to neurodegenerative issues during aging1,2, the proposed studies will test the central hypothesis that cerebellum and basal ganglia are selectively disrupted in mid-aged and older adults with ASD, and this disruption is associated with neuromotor impairments and probable increased clinical features of cerebellar ataxia and Parkinsonism. Using laboratory tests sensitive in detecting these subcortical structural alterations, we will clarify the extent to which neuromotor performance of Romberg stances, quick step initiation, sit-to-stance balance, and goal-directed finger pointing is impacted in adults with ASD aged 40 to 60 years relative to age-, sex- and IQ-matched healthy controls. An innovative two- compartment free-water diffusion magnetic resonance imaging (FWdMRI) will be applied to quantify the neuronal density of cerebellar lobules and basal ganglia nuclei and axonal density of cerebellar peduncles to determine whether these subcortical structures are selectively disrupted in adults with ASD and whether these alterations underpin neuromotor issues. We propose the following specific aims: Aim 1: Determine cerebellar and basal- ganglia related neuromotor deficits in ASD. Aim 2: Determine cerebellar and basal-ganglia structural alterations in ASD. Our group is uniquely qualified to undertake this critical 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. Support from this FOA will allow the team to calculate the success rate of data collection, effect size, and statistic power and to demonstrate the feasibility of recruitment in adults with ASD in order to plan for a full-scale R01 project. This proposal is scientifically 'high risk' as it will be the first to systematically quantify the neuromotor deficits in adults with ASD at the levels of behavior and brain anatomy and to determine the relationships between these impairments and clinical features of cerebellar ataxia and Parkinsonism. If successful, this work holds the greatest promises to be ‘high rewarding’ as it will identify new biobehavioral targets that can be tracked to understand, monitor, and treat conditions related to aging 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）已被认为是终身状况 对成人功能和生活质量产生不利影响的潜力。点1：基于初步 发现ASD患者在老龄化期间可能特别容易受到神经退行性问题的发现1,2， 拟议的研究将检验中心假设，即小脑和基本神经节有选择性破坏 在患有ASD的中年和老年人中，这种干扰与神经运动障碍和 小脑共济失调和帕金森氏症的临床特征可能会增加。使用实验室测试敏感 检测这些皮层结构的改变，我们将阐明神经运动性能的程度 Romberg立场，快速步骤计划，静坐平衡和目标指向指向的指向 相对于年龄，性别和IQ匹配的健康对照组，ASD年龄为40至60岁的成年人。创新的两个 隔室自由水扩散磁共振成像（FWDMRI）将用于量化神经元 小脑小叶的密度和基本的神经节核和小脑子花梗的轴突密度确定 ASD成年人是否有选择地破坏这些皮层结构以及这些改变是否会破坏 基础神经运动问题。我们提出以下具体目的：目标1：确定小脑和基本 - 神经节与ASD相关的神经运动防御。 AIM 2：确定小脑和基本的ganglia结构改变 在ASD中。我们的小组具有独特的资格进行这项关键项目，因为它包括具有专业知识的调查员 和ASD，ASD诊断，衰老和运动障碍，MRI的感觉运动神经生理学的经验 物理和研究以及生物统计学。该FOA的支持将使团队能够计算成功率 数据收集，效果规模和统计能力的 为了计划一个全面的R01项目，ASD。该建议在科学上是“高风险”，因为它将是第一个 系统地量化神经运动的定义在行为和大脑解剖学水平的成年人中定义 并确定这些障碍和小脑共济失调和临床特征之间的关系 帕金森主义。如果成功，这项工作将拥有最大的承诺将是“高度回报”，因为它将确定新的 可以跟踪以理解，监测和治疗与ASD衰老有关的生物行为靶标。