ABSTRACT – Project 2: Neural signatures, developmental precursors, and outcomes in young children with ASD and ADHD Although recognized as distinct diagnostic conditions, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly comorbid. The overlap in clinical presentation, risk factors, and co- heritability of ASD and ADHD has led some authors to propose that these disorders share underlying biological mechanisms and that ADHD is a milder, less severe subtype within the ASD syndrome. Moreover, the presence of co-occurring ADHD has significant clinical implications, where individuals with comorbid ASD and ADHD have substantially poorer outcomes. To date, very little research has focused on the overlap of ASD and ADHD during early childhood. Thus, we know relatively little about the extent to which ASD and ADHD represent distinct conditions or the impact of co-occurring ADHD symptoms on early behavioral patterns and brain mechanisms in ASD. In Project 2, we will study the neural signatures, biomarkers, developmental trajectories, and clinical outcomes associated with comorbid ASD and ADHD with the overarching goal of generating knowledge that will allow earlier detection of these overlapping conditions and more individualized treatment approaches that take into account the additive and interactive effects of both conditions. The primary goals of Project 2 are to (1) elucidate shared and distinct neural signatures and biomarkers related to ASD vs. ADHD, (2) examine the functional and clinical impact of co-occurring ADHD symptoms in young children with ASD, and (3) identify early characteristics of infants and toddlers later diagnosed with ASD with and without elevated ADHD symptoms. To this end, in Project 2, we will recruit four groups of children between 36-72 months of age with the following clinical features: ASD only, ASD+ADHD, ADHD only, and typically-developing (TD) children. The specific aims to achieve our overall study goals are to (1) identify differences and commonalities in neural signatures and biomarkers based on neurophysiology and eye-gaze tracking across the four groups; (2) examine how these biomarkers are correlated with specific symptom profiles based on shared and distinct phenotypic characteristics of ASD and ADHD; (3) determine the clinical impact of ADHD in young children with ASD; and (4) explore the extent to which developmental precursors linked to diagnostic outcome can be detected during the infant-toddler period. The latter aim will be accomplished by analyzing home video recordings taken in the first and second year of life of children later diagnosed with ASD only, ADHD only, ASD+ADHD, vs. TD, based on observations made via automated computer vision analysis of movement and affect, as well as human coding of vocalizations/verbalizations, joint attention, gaze and orienting behavior, affect, and repetitive behaviors. Project 2 will provide a detailed, comprehensive understanding of unique developmental trajectories and impacts of co-occurring ADHD in children with ASD.