Dysfunctional feedback processing in male methamphetamine abusers: Evidence from neurophysiological and computational approaches

Methamphetamine use disorder (MUD) as a major public health risk is associated with dysfunctional neural feedback processing. Although dysfunctional feedback processing in people who are substance dependent has been explored in several behavioral, computational, and electrocortical studies, this mechanism in MUDs requires to be well understood. Furthermore, the current understanding of latent components of their behavior such as learning speed and exploration -exploitation dilemma is still limited. In addition, the association between the latent cognitive components and the related neural mechanisms also needs to be explored. Therefore, in this study, the underlying neurocognitive mechanisms of feedback processing of such impairment, and age/gendermatched healthy controls are evaluated within a probabilistic learning task with rewards and punishments. Mathematical modeling results based on the Q -learning paradigm suggested that MUDs show less sensitivity in distinguishing optimal options. Additionally, it may be worth noting that MUDs exhibited a slight decrease in their ability to learn from negative feedback compared to healthy controls. Also through the lens of underlying neural mechanisms, MUDs showed lower theta power at the medial -frontal areas while responding to negative feedback. However, other EEG measures of reinforcement learning including feedback -related negativity, parietal -P300, and activity flow from the medial frontal to lateral prefrontal regions, remained intact in MUDs. On the other hand, the elimination of the linkage between value sensitivity and medial -frontal theta activity in MUDs was observed. The observed dysfunction could be due to the adverse effects of methamphetamine on the cortico-striatal dopamine circuit, which is reflected in the anterior cingulate cortex activity as the most likely region responsible for efficient behavior adjustment. These findings could help us to pave the way toward tailored therapeutic approaches.