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Abundant evidence from animal models implicates the circadian system in modulating the brain’s reward circuitry, but evidence in humans has been more limited. In particular, published evidence has relied on self-report and/or behavioral proxies of circadian misalignment and cross-sectional designs. Here, we employed objective measures and a prospective design to assess whether circadian alignment predicts the neural response to reward in a sample of late adolescent drinkers. Methods Participants included 23 late adolescents (18–22 y/o; 14 females) reporting weekly alcohol use. Participants completed pre-weekend (Thursday) circadian phase assessments via the dim light melatonin onset (DLMO). Sleep-wake timing was assessed via wrist actigraphy (midpoint of sleep on Tuesday and Wednesday prior to DLMO assessment). Circadian alignment was operationalized as the DLMO-midsleep interval. Neural response to reward was assessed via a card-guessing monetary reward fMRI task; analyzed on reward anticipation and reward win relative to neutral conditions. Mean BOLD signal was extracted from two regions-of-interest (striatum and medial prefrontal cortex, mPFC) for analyses in regression models, accounting for sex and scan order (participants also completed scans on Monday in counterbalanced order, not reported here). Results Shorter DLMO-midsleep intervals (i.e., greater misalignment) predicted lower striatal response to anticipated reward (beta=0.48,p=0.02) and showed a trend towards predicting lower mPFC response to anticipated reward (beta=0.39,p=0.06). No statistically-significant effects were found for reward win. Notably, a lower striatal response to anticipated reward correlated with more binge-drinking episodes in the past 30 days, but was not associated with alcohol use in the weekend immediately following the scan. Conclusion Our findings provide preliminary evidence of proximal associations between objectively-determined circadian alignment and the neural response to anticipated monetary reward. Ongoing work in a larger sample of adolescents aims to replicate this finding and more definitively determine its relevance to adolescent drinking. Support This work was supported by the National Institute on Alcohol Abuse and Alcoholism (R21 AA023209; R01 AA025626).

0068 Circadian Alignment Predicts Neural Response to Monetary Reward in Late Adolescent Drinkers