Learning from alcohol rewards: Neural signatures of drug-related reward prediction errors in alcohol use disorder

Altered neural reward prediction error (RPE)-encoding during learning from drug reinforcers compared to non-drug rewards is at the core of learning theories of addiction. They predict stronger RPE-related fronto-striatal activation when responding for alcohol-related compared to natural rewards, particularly in individuals with alcohol use disorder (AUD). However, research in AUD has largely relied on paradigms that used monetary reinforcers or did not include a learning component. Here, we developed an instrumental learning task (ILT) where correct choices were reinforced by alcohol or juice taste in separate blocks. Twenty-eight individuals with predominantly mild to moderate AUD and 28 healthy control participants (HC) performed the ILT during functional magnetic resonance imaging. Alcohol taste was perceived as less pleasant and elicited less craving than juice taste across groups, and this was driven by HC. Both groups, but particularly individuals with AUD, successfully learned to respond for both reinforcer types, and individuals with AUD, but not HC, became faster over time in alcohol blocks. However, we found no differences in fronto-striatal RPE-encoding between groups and reinforcer types in the expected direction, but instead an opposite effect in dorsolateral prefrontal cortex. While we demonstrate that instrumental learning from alcohol taste elicits RPE-related fronto-striatal activation in AUD and HC, our findings do not support stronger fronto-striatal RPE-encoding when learning from alcohol-related compared to natural reinforcers in individuals with AUD than HC. Future learning research in addiction should take further steps to increase ecological validity by considering the context-dependence of drug-related reinforcers’ rewarding properties.