Enhanced Alcohol-Specific but not General Pavlovian-to-Instrumental Transfer in Alcohol Use Disorder

Background: Pavlovian-to-instrumental transfer (PIT) paradigms assess how environmental cues influence instrumental behaviour. Our previous research linked PIT to alcohol use disorder (AUD) and high-risk drinking using monetary rewards during learning. To better capture alcohol-related cue effects, we developed a PIT paradigm delivering trial-by-trial alcohol and juice rewards alongside monetary rewards, to examine alcohol-specific and general PIT effects in parallel. Methods: Seventy-five participants with AUD and ninety-five controls completed the task during functional magnetic resonance imaging. Alcohol-specific PIT was defined as increased alcohol choices during presentation of alcohol-associated versus juice-associated cues. General PIT was defined as increased response vigor during gain- versus loss-associated cues. Behavioural and neural associations with AUD status and AUDIT scores from baseline through one-year follow-up were examined. Results: Participants with AUD showed stronger alcohol-specific PIT effect than controls. Alcohol-specific PIT was positively associated with baseline AUDIT scores and with AUDIT scores across the one-year follow-up. Alcohol cues elicited stronger anterior insula responses, and region-of-interest analysis showed greater left amygdala responses to alcohol versus juice cues in AUD compared with controls. In contrast, general PIT showed a negative association with AUDIT but no association with AUD status. In the general PIT, no AUD-related neural differences were observed. Conclusions: These findings suggest that alcohol-specific PIT captures a clinically meaningful mechanism of cue-driven alcohol seeking that is distinct from generalized motivational transfer, supporting its potential utility as a mechanistic marker in AUD.