The Role of Pavlovian Bias in Smoking Cessation Success and Neurocognitive Alterations During Nicotine Withdrawal.

Background: Inability to manage conflicts between multiple decision-making systems is associated with various mental disorders including addiction. The imbalance between the Pavlovian and instrumental systems may contribute to smoking cessation failure and relapse, as excessive Pavlovian motivation may override goal-directed quitting attempts. However, the exact role of the Pavlovian bias in smoking cessation and its neurocognitive mechanisms remain poorly understood. Methods: Eighty-six smokers participated in a smoking cessation clinic, completing the well-established orthogonalized go-nogo task before and after the intervention. We applied computational modeling and functional magnetic resonance imaging (fMRI) analyses to investigate the role of Pavlovian bias and its neural correlates in predicting smoking cessation outcomes. Results: Computational modeling revealed that higher levels of Pavlovian bias were associated with treatment failures. Importantly, Pavlovian bias significantly moderated the relationship between clinic participation rate and the likelihood of smoking cessation, suggesting that such bias can undermine motivational effort to quit. Furthermore, individuals who successfully quit smoking exhibited increased Pavlovian bias toward reward following cessation, indicating a potential cognitive mechanism underlying the relapse cycle. Complementary fMRI analyses demonstrated that Pavlovian bias influenced valence encoding in the ventromedial prefrontal cortex (vmPFC), suggesting altered decision-making neural circuits. Conclusions: Pavlovian bias can be a critical risk factor of relapse in the smoking population, while this bias can be increased in response to nicotine abstinence. Moreover, the results highlight the roles of the vmPFC in decision-making under Pavlovian-instrumental conflict, providing insights into the neural underpinnings of relapse vulnerability. Understanding these mechanisms may guide targeted interventions to enhance smoking cessation outcomes.