“…Strategic over-sampling of "rare" cases (e.g., people with LS to alcohol who endorse light alcohol use, people with HS to alcohol who endorse heavier or more problematic alcohol use) also may be useful. Furthermore, longitudinal studies spanning the developmental trajectory of alcohol use will be critical for isolating the effects of sensitivity vs. use on neural ACR because sensitivity and use may covary over time (e.g., innate LS to alcohol may promote heavier use, but heavier use itself may lead to acquired LS to alcohol [i.e., tolerance]) [ 89 ]. Longitudinal studies of neural ACR also are important because incentive sensitization and other theorized neurobiological mechanisms of the addiction cycle posit progressive accumulation functional neuroadaptations with chronic use [ 90 , 91 ], which should be evident as within-person changes in neural ACR and may be obscured in case-control studies by high between-person variability in neural ACR.…”