PROJECT ABSTRACT/SUMMARY Attention-deficit-hyperactivity-disorder (ADHD) affects nearly one in ten school-aged children. Although poor sleep is reported in this condition and has been related to waking behavioral struggles of children with ADHD, little is known about whether and how waking physiological sleepiness per se contributes to these behavioral profiles. Indeed, other than sleep-related breathing disorders, mechanisms underlying poor sleep and consequent physiological sleepiness are unknown. We propose two mechanistic targets within the sleep regulatory domain to tie together daytime sleepiness and learning outcomes in ADHD. Thus, this COBRE project uses an innovative laboratory study of operationally defined sleepiness, mechanisms of sleep regulation and circadian timing, and working memory (critical for learning success in the classroom) in children with and without ADHD. Our central hypothesis is that children with ADHD have underlying differences in Process S, sleep homeostasis, and Process C, circadian timing. Our methodology will be to enroll n=100, 9-11 year-old children (IQ ≥ 80), 50 with confirmable ADHD and 50 typically developing controls (TDCs) into a laboratory study. Following 2-weeks at home on a sleep schedule conforming to current recommendations (9 hours in bed) each child will come to the laboratory for three consecutive nights and days. All sleep in the lab will be monitored by polysomnography. Across a set of aims we will examine mechanisms of sleep and circadian regulatory processes, the level and pattern of physiological sleepiness per se, and the cognitive consequences of sleepiness, i.e., working memory. Together, these aims will serve to increase knowledge about the association of sleep homeostasis and circadian timing with ADHD symptoms, identify the role of physiological sleepiness in waking performance of children with ADHD, and determine whether sleep homeostasis regulation and/or circadian timing influence these outcomes. Our project will potentially inform innovative interventions that may target sleepiness in children with ADHD while preparing the project leader for an independent career at the intersection of sleep and clinical neurodevelopmental science.