Dysfunctional feedback processing in methamphetamine abuser; evidence from neurophysiological and computational analysis

Methamphetamine use disorder associated with a dysfunctional neural feedback (reward-punishment) processing system and is considered a public health risk. Although several behavioral, computational, and electrocortical studies have explored feedback processing in other groups of individuals, the precise mechanisms of feedback processing dysfunction in methamphetamine use dependent (MUD) individuals remain unclear. Furthermore, our recent knowledge about the underlying feedback-related connectivity patterns and intertwining latent components of behavior with electrocortical signals in MUDs remained quite poor. The present study intended to fill these gaps by exploring the behavioral and electrocortical responses of abstained MUDs during a feedback-based learning paradigm. As mathematical models revealed, MUDs have less sensitivity to distinguishing optimal options (less sensitivity to options value) and learned less from negative feedback, compared with healthy controls. The MUDs also presented smaller medial-frontal theta (5-8 Hz) oscillations in response to negative feedback (300-550 ms post feedback) while other measures responsible for learning including, feedback-related negativity (FRN), parietal-P300, and a flux originated from medial frontal to lateral prefrontal remained intact for them. Further, in contrast to healthy controls, the observed association between feedback sensitivity and medial-frontal theta activity is eliminated in MUDs. We suggested that these results in MUDs may be due to the adverse effect of methamphetamine on the cortico-striatal dopamine circuit, reflected in anterior cingulate cortex (ACC) activity as the best candidate region responsible for efficient behavior adjustment. This study unveils the underlying neural mechanism of feedback processing in individuals with methamphetamine use history and could offer individual therapeutic approaches.