Neural mechanisms of speech motor control in Autism Spectrum Disorders

项目摘要 言语障碍是自闭症患者最普遍和最有害的症状之一 自闭症（ASD）。事实上，25%的ASD患者几乎不说话。很多ASD患者 我们对语言的斗争仍然知之甚少，这意味着我们的治疗并没有针对语言的来源。 问题.我们的初步工作已经证明，改变听觉反馈可以影响言语， ASD患者。然而，将这些发现转化为新的治疗方法的能力， ASD中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 ASD患者的运动控制在本研究中，我们将使用行为任务和多种方法 先进的大脑成像技术，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 以确定自闭症患者言语产生的具体障碍。 具体来说，我们将首先描述儿童语言运动控制的心理物理和神经标志， 有和没有ASD的青少年（目标1）。然后，我们将确定语言运动控制的机制， 与言语障碍的临床症状相关（目标2）。使用脑磁图，功能 MRI和磁共振波谱分析，然后我们将研究临床语言能力和大脑之间的关系 代谢物和连接的言语运动网络（目的3）。该项目的成果不仅有助于 解释为什么有些ASD患者很难说话，但也会为有针对性的发展打开大门。 治疗，以解决问题的根源，这可能会大大扩大的影响， 目前的语言治疗，甚至从根本上改变自闭症儿童的语言预后。

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.