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.

项目总结/摘要 虽然概念上是一种神经发育障碍，目前的研究主要集中在婴儿身上， 自闭症谱系障碍（ASD）越来越被认为是一种终身疾病， 可能对成人功能和生活质量产生不利影响。第1点：根据初步 发现ASD患者在衰老过程中可能特别容易受到神经退行性问题的影响1，2， 这项研究将验证小脑和基底神经节被选择性破坏的中心假设。 在患有ASD的中年和老年人中，这种破坏与神经运动障碍有关， 小脑性共济失调和帕金森综合征的临床特征可能增加。使用敏感的实验室测试， 检测这些皮层下结构的改变，我们将阐明在何种程度上，神经运动的表现， Romberg站姿、快速起步、坐姿到站姿平衡和目标指向的手指指向受到影响， 与年龄、性别和智商匹配的健康对照相比，年龄在40至60岁之间的ASD成年人。一个创新的二- 将应用隔室自由水扩散磁共振成像（FWdMRI）来量化神经元的 小脑小叶和基底节核的密度以及小脑脚的轴突密度来确定 这些皮质下结构是否在患有ASD的成年人中被选择性地破坏，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：确定小脑和基底神经节的结构改变 在ASD我们的团队是唯一有资格承担这一关键项目，因为它包括具有专业知识的调查人员 在ASD的感觉运动神经生理学、ASD诊断、衰老和运动障碍、MRI方面的经验 物理学和研究，以及生物统计学。来自此FOA的支持将允许团队计算成功率 数据收集，效应量和统计功效，并证明招募成年人的可行性， ASD，以便规划全面的R 01项目。这项提议在科学上是“高风险”的，因为它将是第一个 在行为和大脑解剖学水平上系统地量化ASD成年人的神经运动缺陷 并确定这些损伤与小脑共济失调的临床特征之间的关系， 帕金森症。如果成功的话，这项工作最有希望成为“高回报”，因为它将发现新的 生物行为目标，可以跟踪，以了解，监测和治疗与ASD老化相关的条件。