Project SummaryChildren’s early externalizing behavior problems, including symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) such as inattention, hyperactivity, and impulsivity,are the most common reason for early childhood mental health referrals and occur in 10-25% of preschoolers. Despite the successful development of evidence-based treatmentsfor ADHD, early interventions have been shown to have little impact on children’s long-term academic and social impairment. A major barrier to understanding the long-termtreatment impact on children with ADHD is that current definitions of the disorder relysolely on DSM-V symptom profiles. A simplistic classification system limits ourunderstanding of the heterogeneity present in ADHD, particularly during the preschool andearly elementary school years. The heterogeneity of the disorder suggests that the ADHDmay be characterized by multiple subgroups with varying neuropsychological profiles, withthe assumption is that these profiles reflect different underlying neurobiological substrates.However, an established understanding of the neurobiology of ADHD is lacking, inparticular, in the executive function (EF) and emotion regulation (ER) domains. Inaccordance with the NIMH strategic plan (Strategy 1.4) we seek to overcome theselimitations by identifying distinct “biosignatures” derived from an integration ofneurobiological (functional and structural magnetic resonance imaging (MRI); functionalMRI and diffusion-weighted MRI) and pathophysiological markers of EF and ER. This willaid in the early identification and tailored treatment of behavioral and neuropsychologicalphenotypes of ADHD. Additionally, we propose to examine the extent to which theidentified “biosignatures” predict children’s early intervention response. Understandingand better capturing the heterogeneity of EF and ER may lead to more targeted treatmentsto improve children with ADHD’s social and academic functioning.