Pilot Project Core (Core PI: John Krystal, M.D.) Abstract This Core provides limited funding to investigators to collect pilot data for innovative research projects. These projects serve CTNA by 1) testing key hypotheses or methodologies, 2) bringing new investigators into CTNA, 3) generating new alcohol RO1s, 4) enabling CTNA to rapidly adapt to advances, and 5) guiding the CTNA renewal. Proposals are solicited openly and developed in consultation with CTNA Cores (Clinical, Translational Technologies). Three of the proposed projects proposed are from young investigators who are new to alcohol research and one is from an NIAAA K- awardee (A.H.): 1) PP1 (Yr1): Ansel Hillmer Ph.D. tests whether family history of alcoholism (FHP) is associated with alterations in an in vivo PET marker of cortical synaptic density and through this mechanism influences alcohol response; 2) PP2 (Yr1): Gihyun Yoon, M.D. tests whether a novel NMDA-R modulating strategy (D-serine plus a D-serine metabolism inhibitor, sodium benzoate) reduces intravenous ethanol self-administration in human heavy drinkers. 3) PP3 (Yr2) John Murray, Ph.D. proposes a computational neuroscience study that uses resting state fMRI data (ABCD Study) to generate maps associated with the polygenic risk score for alcohol use disorder and then convolve these maps upon transcriptomic profiles for target risk genes. 4) PP4 (Yr2) Jose Cortes-Briones, Ph.D. collects EEG/fMRI in FHP/FHN healthy subjects at rest and during alcohol consumption and then applies machine learning approaches to characterize functional connectivity and spectral power “fingerprints” that distinguish these groups. Pilot projects for years 3-5 will be identified and reviewed through the steps outlined in this Core.