Behavioral and Neural Signatures of Reduced Updating of Alternative Options in Alcohol-Dependent Patients during Flexible Decision-Making.

Addicted individuals continue substance use despite the knowledge of harmful consequences and often report having no choice but to consume. Computational psychiatry accounts have linked this clinical observation to difficulties in making flexible and goal-directed decisions in dynamic environments via consideration of potential alternative choices. To probe this in alcohol-dependent patients (n = 43) versus healthy volunteers (n = 35), human participants performed an anticorrelated decision-making task during functional neuroimaging. Via computational modeling, we investigated behavioral and neural signatures of inference regarding the alternative option. While healthy control subjects exploited the anticorrelated structure of the task to guide decision-making, alcohol-dependent patients were relatively better explained by a model-free strategy due to reduced inference on the alternative option after punishment. Whereas model-free prediction error signals were preserved, alcohol-dependent patients exhibited blunted medial prefrontal signatures of inference on the alternative option. This reduction was associated with patients' behavioral deficit in updating the alternative choice option and their obsessive-compulsive drinking habits. All results remained significant when adjusting for potential confounders (e.g., neuropsychological measures and gray matter density). A disturbed integration of alternative choice options implemented by the medial prefrontal cortex appears to be one important explanation for the puzzling question of why addicted individuals continue drug consumption despite negative consequences. SIGNIFICANCE STATEMENT: In addiction, patients maintain substance use despite devastating consequences and often report having no choice but to consume. These clinical observations have been theoretically linked to disturbed mechanisms of inference, for example, to difficulties when learning statistical regularities of the environmental structure to guide decisions. Using computational modeling, we demonstrate disturbed inference on alternative choice options in alcohol addiction. Patients neglecting "what might have happened" was accompanied by blunted coding of inference regarding alternative choice options in the medial prefrontal cortex. An impaired integration of alternative choice options implemented by the medial prefrontal cortex might contribute to ongoing drug consumption in the face of evident negative consequences.