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.