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Counterconditioning Alcohol Cues: Neural and Behavioral Modulation of Automatic Tendencies and Pavlovian-to-Instrumental Transfer in Male Alcohol Users

Verma, A. K.; Chivukula, U.; Garbusow, M.; Kumar, N.

2025-11-11 neuroscience
10.1101/2025.11.10.687519 bioRxiv
Show abstract

Repeated alcohol-cue pairings with rewarding experiences establish automatic response tendencies that bias instrumental behavior through Pavlovian-to-instrumental transfer (PIT). How individual differences in approach and avoidance tendencies shape PIT and intervention responsiveness remains poorly understood. This study examined whether automatic tendencies differentially modulate PIT, and whether counterconditioning (CC) combined with retrieval cues can attenuate approach biases and cue-driven instrumental interference. Thirty-nine male alcohol users completed an Alcohol Approach-Avoidance Task and PIT task before and after CC, classified into approach or avoidance groups based on their baseline Alcohol Approach Index. Alcohol cues were paired with monetary loss during CC, with retrieval cues introduced to facilitate reactivation of newly formed aversive associations. Right frontal N2 and centroparietal P3 were examined as indices of early evaluative and attentional processing. Despite comparable behavioral PIT performance, approach-oriented individuals showed attenuated right frontal N2 during push actions at baseline, reflecting reduced frontal regulatory engagement during cue-incongruent responding. CC selectively reduced approach biases in the approach group, with retrieval cues producing additional reductions, accompanied by N2 and P3 restoration. CC recalibrated PIT interference by reducing push and increasing pull interference, particularly with retrieval cues. CC-induced changes in approach bias did not predict PIT interference, suggesting modulation through partially dissociable pathways. CC with retrieval cues selectively reduced approach biases and recalibrated cue-driven instrumental interference in approach-oriented individuals, providing proof-of-concept for retrieval cue-integrated CC as a targeted associative intervention and highlighting the importance of individual tendency profiles in intervention responsiveness.

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