Abnormal DLPFC activation in severe methamphetamine use disorder during abstinence: fNIRS evidence from Stroop task.

INTRODUCTION: Methamphetamine use disorder (MUD) is a chronic relapsing disorder characterized by impaired inhibitory control, particularly in severe cases. However, the neural mechanisms underlying cognitive control during abstinence remain unclear. METHODS: This study employed functional near-infrared spectroscopy (fNIRS) and the Stroop task to examine brain activation and behavior in 73 abstinent individuals with severe MUD (SMUDs) and 51 matched healthy controls (HCs). Independent-samples t-tests assessed group differences, with false discovery rate correction across fNIRS channels. Covariate-adjusted sensitivity analyses controlled for education and Alcohol Use Disorders Identification Test scores. Moderation analysis examined whether abstinence duration modified activation-behavior associations. Pearson correlations and Fisher's r-to-z tests examined direct and subgroup associations. RESULTS: SMUDs showed reduced activation in channels 32 and 43 (CH32 and CH43) within the left dorsolateral prefrontal cortex (DLPFC) compared with HCs, despite no significant group differences in conventional Stroop behavioral indices. These activation differences remained significant after covariate adjustment. Abstinence duration significantly moderated the association between CH43 activation and the reaction-time difference score (DRT; incongruent RT minus congruent RT), whereas abstinence duration was not directly correlated with CH43 activation. The positive association between CH43 activation and DRT was significant at shorter abstinence durations but not at longer abstinence durations. DISCUSSION: These findings reveal left DLPFC hypoactivation and altered neural-behavioral coupling in SMUDs. The observed DLPFC hypoactivation remained robust after adjustment for education and AUDIT scores, consistent with persistent SMUD-related prefrontal dysfunction. Moreover, early abstinence may be characterized by altered or less efficient activation-behavior coupling, highlighting this stage as a potential window for targeted neuromodulatory interventions aimed at supporting cognitive recovery.