People with a tobacco use disorder misattribute non-drug cues as worse predictors of positive outcomes compared to drug cues

Adaptive behaviours depend on dynamically updating internal representations of the world based on the ever-changing environmental contingencies. People with a substance use disorder (pSUD) show maladaptive behaviours with high persistence in drug-taking, despite severe negative consequences. We recently proposed a salience misattribution model for addiction (SMMA; Kalhan et al., (2021)), arguing that pSUD have aberrations in their updating processes where drug cues are misattributed as strong predictors of positive outcomes, but weaker predictors of negative outcomes. We also argue that conversely, non-drug cues are misattributed as weak predictors of positive outcomes, but stronger predictors of negative outcomes. However, these hypotheses need to be empirically tested. Here we used a multi-cue reversal learning task, with reversals in whether drug or non-drug cues are currently relevant in predicting the outcome (monetary win or loss). We show that compared to controls, people with a tobacco use disorder (pTUD), do form misaligned internal representations. We found that pTUD updated less towards learning the drug cues relevance in predicting a loss. Further, when neither drug nor non-drug cue predicted a win, pTUD updated more towards the drug cue being relevant predictors of that win. Our Bayesian belief updating model revealed that pTUD had a low estimated likelihood of non-drug cues being predictors of wins, compared to drug cues, which drove the misaligned updating. Overall, several hypotheses of the SMMA were supported, but not all. Our results implicate that strengthening the non-drug cue association with positive outcomes may help restore the misaligned internal representation in pTUD.