Modulating Prefrontal Cortex Activity to Alleviate Stress-Induced Working Memory Deficits: A Transcranial Direct Current (tDCS) Study

This study explores the impact of stress on working memory (WM) performance, and the potential mitigating effects of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC). The study had a crossover, randomized, single-blind, sham-controlled design, with stress induction as within-subject and stimulation condition as between-subject factors. We assessed stress-induced WM deficits using aversive video clips to induce stress and a verbal n-back task to assess WM performance. We analyzed physiological (cortisol and heart rate), behavioral, and electroencephalographic (EEG) changes due to stress before, during, and after WM task performance and their modulation by tDCS. Stress impaired WM performance in the sham stimulation condition for the 3-back load, but not for 2-back or 4-back loads in the WM task, and was associated with elevated physiological stress markers. tDCS over the vmPFC led to better WM task performance while stimulation over the dlPFC did not. Active tDCS with both dlPFC and vmPFC stimulation blunted cortisol release in stress conditions compared to sham. The EEG analysis revealed potential mechanisms explaining the behavioral effects of vmPFC stimulation. vmPFC stimulation led to a decreased P200 event-related potential (ERP) component compared to the sham stimulation condition and resulted in higher task-related alpha desynchronization, indicating reduced distractions and better focus during task performance. This study thus shows that the vmPFC might be a potential target for mitigating the effects of stress on WM performance, and contributes to the development of targeted interventions for stress-related cognitive impairments. Significance StatementThis study investigates how stress impacts working memory performance and whether non-invasive brain stimulation can mitigate these effects. Using transcranial direct current stimulation (tDCS), we targeted specific brain areas in participants stressed by watching aversive videos. Stress reduced working memory performance and increased cortisol levels. However, tDCS applied to the ventromedial prefrontal cortex (vmPFC) improved task performance and blunted the cortisol response compared to a sham treatment. EEG data suggest that stimulation also enhanced focus during task performance and reduced emotional distraction. Our findings suggest that tDCS over the vmPFC could be a promising non-invasive brain stimulation method to counteract the negative effects of stress on cognitive functions.