Neural mechanisms of speech motor control in Autism Spectrum Disorders

项目总结 言语障碍是自闭症患者最常见和最严重的症状之一 精神障碍(ASD)。事实上，25%的自闭症患者很少或根本不会说话。许多患有自闭症的人 人们对说话的困难仍然知之甚少，这意味着我们的治疗方法并不针对 有问题。我们的初步工作表明，改变听觉反馈可以影响人的语音 患有自闭症的个体。然而，将这些发现转化为开发新的治疗方法的能力 我们对听觉反馈如何与言语相互作用的有限理解阻碍了自闭症患者的言语缺陷 ASD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。 具体地说，我们将首先表征儿童言语运动控制的心理物理和神经标志，以及 患有和不患有自闭症的青少年(目标1)。然后我们将确定语音运动控制的机制， 与言语障碍的临床症状有关(目标2)。使用脑磁图，功能性 核磁共振成像和磁共振波谱，然后我们将检查临床语言能力和大脑之间的关系 语言运动网络中的代谢物和连接性(目标3)。该项目的结果不仅将有助于 解释为什么一些ASD患者难以说话，但也会为针对性的发展打开大门 首次解决问题根源的治疗方法，这可能会极大地扩大 目前的言语疗法甚至从根本上改变了患有自闭症的少言寡语儿童的预后。

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.