ABSTRACT – PROJECT 2: Impact of Adolescent Vaping on Brain Health There is growing concern that vaping nicotine may affect brain health during adolescence, a period of rapid maturation. Nicotine directly affects nicotinic cholinergic receptors throughout the nervous system resulting in functional changes in many late developing brain regions, including areas implicated in attention, memory, executive function, social cognition, and emotion processing. Prior research established that nicotine (in animal models) and smoking (in humans) affects brain structure and function; cognitive and psychosocial function; and autonomic regulation. However, very little is known about how vaping nicotine, including frequency of use, product characteristics, and cumulative exposure, impacts adolescent brain health. Furthermore, other chemical constituents of vaping aerosols (e.g., acrolein) that could also affect brain development. Our overarching hypothesis is that vaping affects brain health in specific regions/networks and associated cognitive/psychosocial domains related to attention, memory, executive function, social cognition, and emotion processing. Our novel mechanistic hypothesis is that the effects of vaping on the brain are related to shifts in autonomic nervous system towards increased sympathetic and diminished parasympathetic tone with associated changes in cerebral blood flow and connectivity in regions and networks of interest. Our three Specific Aims are 1) Determine the effects of vaping on brain function and structure in adolescents; 2) Examine the effects of vaping on cognitive and psychosocial development, 3) Assess the effects of vaping on autonomic nervous system function. We will assess 360 adolescents recruited from the longitudinal Online Survey for a Lab-Based Study, using a 2:1 ratio of Current Vapers to Never Tobacco Users, minimizing potential confounds with additional exclusion criteria (e.g., marijuana use). Participants will be tested at a 2 time points, 18 months apart. This study will be the first and largest to date that longitudinally quantifies key physiological and developmental changes associated with adolescent vaping, providing data on the impact of vaping on brain structural/functional, cognitive and psychosocial maturation and autonomic nervous system function. The findings from Project 2 will be utilized by Project 4 as potential targets for vaping prevention messages.