Neural mechanisms of speech motor control in Autism Spectrum Disorders

自闭症谱系障碍言语运动控制的神经机制

• 批准号: 10299542
• 负责人: Carly Demopoulos
• 金额: $ 68.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-02 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10299542
• 关键词: Address; Adolescent; Affect; Age; Auditory area; Behavioral; Brain; Brain imaging; Chemicals; Child; Clinical; Communication; Control Groups; Cross-Sectional Studies; Data; Development; Feedback; Financial compensation; Functional Magnetic Resonance Imaging; Functional disorder; Glutamates; Goals; Hearing problem; Heterogeneity; Impairment; Individual; Language; Lead; Learning; Link; Literature; Magnetic Resonance Spectroscopy; Magnetoencephalography; Measures; Methods; Modeling; Motor; Motor Cortex; Neuropsychology; Neurotransmitters; Participant; Pathologic Processes; Pathology; Pattern; Performance; Process; Production; Prognosis; Psychophysics; Reproducibility; Rest; Socialization; Source; Speech; Speech Therapy; Standardization; Symptoms; System; Testing; Time; Translating; Work; auditory feedback; auditory processing; autism spectrum disorder; autistic children; clinical phenotype; gamma-Aminobutyric Acid; indexing; individuals with autism spectrum disorder; motor control; neuromechanism; novel; novel strategies; relating to nervous system; response; sensory feedback; speech accuracy; theories

PROJECT SUMMARY Speech deficits are among the most prevalent and impairing of symptoms for people with Autism Spectrum Disorder (ASD). In fact, 25% of people with ASD have little to no speech. The reasons many people with ASD struggle to speak are still poorly understood, which means that our treatments don't target the source of the problem. Our preliminary work has demonstrated that altering auditory feedback can influence speech in individuals with ASD. However, the ability to translate these findings to the development of novel treatments for speech deficits in ASD is impeded by our limited understanding of how auditory feedback interacts with speech motor control in individuals with ASD. In the proposed study, we will use behavioral tasks and multiple methods of advanced brain imaging to understand how brain chemicals and brain function impact a child's ability to speak in order to identify the specific barriers to speech production for people with ASD. Specifically, we will first characterize psychophysical and neural markers of speech motor control in children and adolescents with and without ASD (Aim 1). We will then identify the mechanisms of speech motor control that are associated with clinical symptoms of speech impairment (Aim 2). Using magnetoencephalography, functional MRI and MR spectroscopy, we will then examine the relations between clinical speech abilities and brain metabolites and connectivity in the speech motor network (Aim 3). The results of the project will not only help explain why some people with ASD struggle to speak but will also open doors for development of targeted treatments to address the source of the problem for the first time, which could dramatically extend the impact of current speech therapies and even fundamentally change the prognosis for minimally verbal children with autism.

项目概要 言语缺陷是自闭症谱系患者最常见和最严重的症状之一 障碍（自闭症谱系障碍）。事实上，25% 的自闭症谱系障碍患者几乎没有言语能力。许多患有自闭症谱系障碍 (ASD) 的人的原因 对于说话困难的问题仍然知之甚少，这意味着我们的治疗并没有针对言语困难的根源 问题。我们的初步工作表明，改变听觉反馈可以影响言语 患有自闭症谱系障碍 (ASD) 的人。然而，将这些发现转化为新疗法的开发的能力 自闭症谱系障碍患者的言语缺陷受到我们对听觉反馈如何与言语相互作用的有限理解的阻碍 自闭症谱系障碍患者的运动控制。在拟议的研究中，我们将使用行为任务和多种方法 先进的大脑成像，以了解大脑化学物质和大脑功能如何影响儿童的说话能力 以确定自闭症谱系障碍患者言语产生的具体障碍。 具体来说，我们将首先表征儿童和儿童言语运动控制的心理物理和神经标记。 患有和不患有 ASD 的青少年（目标 1）。然后我们将确定言语运动控制的机制 与言语障碍的临床症状相关（目标 2）。使用脑磁图、功能 MRI 和 MR 波谱学，然后我们将检查临床言语能力与大脑之间的关系 言语运动网络中的代谢和连接（目标 3）。该项目的成果不仅有助于 解释为什么有些患有自闭症谱系障碍的人很难说话，但也会为有针对性的发展打开大门 首次解决问题根源的治疗方法，这可能会大大扩大 目前的言语疗法甚至从根本上改变了语言能力极差的自闭症儿童的预后。