[Background] Cognitive dysfunction is a persistent residual symptom of major depressive disorder (MDD), among which reduced cognitive flexibility is a typical cognitive dysfunction. Patients with cognitive inflexibility have difficulty switching between tasks. This consists of two subcomponents: forgetting old tasks and adapting to new tasks. The present study aimed to examine the subcomponents of cognitive inflexibility in MDD patients separately and to determine whether they can be improved by transcranial direct current stimulation (tDCS) of the prefrontal cortex.
 [Method] The study included 20 patients with MDD and 22 age-matched healthy controls (HCs). In a crossover design, participants received anodal tDCS in either the dorsomedial prefrontal cortex (DMPFC) or the dorsolateral prefrontal cortex (DLPFC). Patients performed a modified Wisconsin Card Sorting Test with explicit task rule switching, and occasional release of proactive interference from the previous task rule was administered before and after adaptation by tDCS.
 [Result] We found that the behavioral cost of a task switch was increased in patients with MDD, but that of proactive interference was comparable between patients with MDD and HCs. The response time for anodal DMPFC tDCS was decreased compared to that for anodal tDCS on the DLPFC in the MDD group. DLPFC tDCS increased the task-switch cost and facilitated responses under no proactive interference.
 [Conclusions] These findings suggest that cognitive inflexibility in MDD is primarily explained by difficulty to adapt to a new task and environment. tDCS in MDD patients has different effects on the improvement of cognitive flexibility response time, depending on the site of stimulation.
 Authors' abstract