The candidate is a committed scientist in optical radiology, who aspires to become an independent investigator focused on developing novel imaging strategies to elucidate underlying mechanisms, inform clinical interventions, and improve outcome of Autism Spectrum Disorder (ASD). Recent advances in functional brain imaging show promise that neural signatures may provide useful markers of ASD severity and may be sensitive to interventional therapy. However, current neuroimaging methods (e.g. functional magnetic resonance imaging, fMRI) are limited in ASD due to the constrained imaging environment. The candidate has been developing diffuse optical tomography (DOT) methods that overcome ergonomic limitations of fMRI and image brain function with a wearable cap. In Aim 1, task-based DOT methods will be established in children with ASD and age/sex/IQ- matched typically developing children (TDC) using a biological motion processing task shown to be sensitive to ASD diagnosis and social ability. In Aim 2, the proposal will employ task-free DOT methods to investigate functional brain organization of in the same subjects as Aim 1. Additionally, Aim 3 of this proposal will extend neuroimaging to three non-overlapping sub-groups of patients with ASD who have been especially challenging to study with fMRI: school-aged children that are minimally verbal, have a low full-scale IQ, or score in the severe range of social ability assessments. These studies will be innovative and significant because the comfortable scanning environment of DOT will enable brain imaging of ASD throughout an extended spectrum of patients, and will lay the groundwork for DOT neuroimaging studies on infants and toddlers at high risk for ASD. The candidate has assembled and has fully engaged a superb interdisciplinary Scholarship Advisory Committee composed of primary mentor Dr. John Constantino, and co-mentors Drs. John Pruett, Bradley Schlaggar, Lori Markson, and Joseph Culver, who are internationally-recognized funded scientists with a diverse range of expertise in ASD research and clinical care, child psychology, neurology, developmental and experimental psychology and functional brain imaging. A well-developed, formal Career Development Program builds on the candidate's extensive experience in physics, systems neuroscience, and technology development by augmenting his current skill set with detailed training in phenotypic assessment and developmental and experimental psychology as they pertain to ASD. This Career Development Award complements the training with world-class coursework in Advanced Cognitive Psychology, Neurobiology of Disease, and Advanced Functional Imaging Methods. The Institution, Washington University School of Medicine, has committed to supporting the candidate by providing the necessary laboratory space and financial resources needed to carry out the proposed research. This training grant will provide the candidate with both the basic science and clinical aspects of autism research, and the critical training period necessary to lead his own independent research effort using optical imaging to address specific questions in ASD.