Reward Prediction Errors Drive Reinforcement Learning and Recognition Memory: Gender Differences in Methamphetamine Abusers.

OBJECTIVES: Methamphetamine (MA) abusers have impaired executive functioning with gender differences, which may be related to the reward prediction errors (RPEs) that drive reinforcement learning and recognition memory, as RPE signaling is impaired in MA abusers. We examined whether the driving effects of RPE on reinforcement learning and recognition memory are impaired in MA abusers and how they differ between women and men. METHODS: Eighty-two MA abusers (43 men, 39 women) from Zhejiang Compulsory Isolation Drug Rehabilitation Center and 86 non-users (45 men, 41 women) from Wenzhou medical university were recruited in this experimental study. We employed a behavioral paradigm adapted from Rouhani et al., which included a learning task and a recognition test. In the learning task, participants underwent a cycle of prediction and feedback, using the outcomes to iteratively adjust their subsequent choices. Reward prediction errors were manipulated by giving different monetary reward feedback after each reward prediction. RESULTS: MA abusers showed significant impairments in learning rates and recognition accuracy compared with non-users. GLMM analysis revealed gender-specific patterns: the moderating effect of group on the RPE-learning relationship was significant in females but not in males, indicating impaired RPE utilization in female abusers. CONCLUSION: These findings suggest that methamphetamine abuse impairs RPE-dependent learning and memory, with reduced RPE utilization efficiency specifically observed in female abusers-manifested as larger prediction errors but lower learning rates.