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 虽然被概念化为神经发育障碍，但目前的研究主要集中在婴儿 对于儿童来说，自闭症谱系障碍(ASD)越来越被认为是一种终生疾病 有可能对成年人的功能和生活质量产生不利影响。要点1：基于初步数据 研究发现，ASD患者在1岁、2岁时可能特别容易出现神经退行性问题， 拟议中的研究将检验中心假设，即小脑和基底节被选择性地破坏。 在患有ASD的中老年人中，这种障碍与神经运动障碍和 可能增加了小脑性共济失调和帕金森氏症的临床特征。使用敏感的实验室测试 检测到这些皮质下结构的改变，我们将澄清神经运动功能在多大程度上 龙伯格的站姿、快步启动、坐姿平衡和目标指向的指点都受到影响 与年龄、性别和智商相匹配的健康对照组相比，年龄在40-60岁之间的ASD成年人。创新的两个- 脑室内游离水弥散磁共振成像(FWdMRI)将被应用于神经元的量化 小脑小叶和基底节核团密度及小脑脚轴突密度测定 在患有ASD的成年人中，这些皮质下结构是否被选择性地破坏，以及这些改变是否 神经运动问题的基础。我们提出了以下具体目标：目标1：确定小脑和基底- ASD中神经节相关的神经运动缺陷。目的2：确定小脑和基底节的结构改变 在ASD中。我们的团队是唯一有资格承担这一关键项目的团队，因为它包括具有专业知识的调查人员 以及在ASD、ASD诊断、衰老和运动障碍、MRI方面的感觉运动神经生理学经验 物理学和研究，以及生物统计学。来自该FOA的支持将使团队能够计算成功率 数据收集、效应大小和统计能力，并证明招募成年人的可行性 ASD，以便计划一个全面的R01项目。这项提议在科学上是“高风险”的，因为它将是第一个 从行为和脑解剖水平系统量化成人ASD患者的神经运动缺陷 并确定这些损害与小脑性共济失调临床特征之间的关系。 帕金森症。如果成功，这项工作将获得最大的回报，因为它将发现新的 可追踪的生物行为指标，以了解、监测和治疗与ASD衰老相关的情况。