Cerebellar and Basal Ganglia Markers Underlie Neuromotor Impairments in Adults with Autism Spectrum Disorder (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。根据临床观察， 患有ASD的中老年成年人在衰老过程中可能特别容易患上神经退行性疾病， 拟议的研究将检验中心假设，即小脑和基底节是选择性的 在40至60岁的ASD成人中中断。而且，这种干扰与神经运动损伤有关 以及运动障碍的临床征兆。自由水扩散磁共振成像(FWdMRI)将 用于量化小脑小叶、齿状核、基底节核和轴突的神经元变性 用小脑脚的完整性来确定成人ASD患者的这些皮质下靶点是否被破坏 相对于年龄、性别和智商匹配的对照组。将使用Precision GRIP的功能磁共振成像(FMRI)进行量化 皮质-皮质下大脑靶点的异常激活以及这些变化是否支持握力 ASD中与生产相关的损害。用神经运动试验灵敏地检测出 小脑和基底节，我们将阐明龙伯格姿势的表现程度，快走 成人自闭症患者的初始平衡、坐姿平衡和目标指向的指手画脚都受到影响。指导原则 强劲的初步数据，我们将追求三个具体目标：目标1)确定结构变化 FWdMRI在成人ASD患者小脑和基底节的应用。目的2)确定患者的功能缺陷 运动功能磁共振成像在成人ASD患者小脑和基底节中的应用。目的3)确定神经运动损伤 在患有ASD的成年人中。我们的团队是唯一有资格承担这一关键R01项目的团队，因为它包括调查人员 在ASD、ASD诊断、衰老和运动方面具有感觉运动神经生理学方面的专业知识和经验 疾病，核磁共振物理和研究，以及生物统计学。这项提议具有科学创新性，因为它将是 首先系统地量化ASD中与衰老相关的神经运动问题，在大脑、行为和 临床领域。这一项目意义重大，因为它有望识别假想的非侵入性特征 皮质下的大脑靶点导致ASD的衰老。如果成功，这项工作将识别新的大脑和 可以追踪的生物行为指标，以了解、监测和治疗ASD中与衰老相关的情况。

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.