Anodal tDCS over right DLPFC does not improve visuospatial working memory in schizophrenia: a single-session, sham-controlled study

Cognitive deficits, particularly in working memory (WM), significantly impair functional outcomes in schizophrenia (SCZ). Transcranial direct current stimulation (tDCS) has shown potential for cognitive enhancement, but its efficacy remains inconsistent. We aimed to evaluate the acute effects of a single-session anodal tDCS over the right dorsolateral prefrontal cortex (rDLPFC) on visuospatial and verbal WM, specifically examining whether baseline performance levels modulate treatment response. In this sham-controlled, within-subject crossover study, 27 clinically stable SCZ patients received 15 min of 1.5 mA anodal tDCS or sham stimulation. WM was assessed pre- and post-stimulation using computerized Corsi Block-Tapping Tasks (CBT) and the Forward Digit Span. Participants were stratified into high- and low-performance subgroups via a median split of baseline CBT scores to investigate baseline-dependent effects. Two-way repeated-measures Analyses of Variance (ANOVA) revealed no significant Session × Time interactions for the majority of WM tasks. A significant two-way interaction was identified for the CBT Backward span [F(1, 26) = 6.011, p = 0.021]; however, post-hoc analysis indicated no significant pre-to-post changes within either the anodal or sham condition. To address potential baseline-dependent effects with greater statistical precision, linear mixed-effects models (LMM) were employed using baseline performance as a continuous moderator. The LMM analysis revealed no significant three-way interactions (Session × Time × Baseline score) across all WM tasks (all p > 0.113), failing to support the hypothesis that initial cognitive capacity significantly moderates the acute response to stimulation. A single session of 1.5 mA anodal tDCS (15 min) over the rDLPFC did not significantly enhance visuospatial or verbal WM performance as measured by offline assessments in clinically stable patients with SCZ, regardless of their baseline cognitive capacity. While our sample size was powered to detect large effects, these null findings suggest that single-target, single-session protocols may be insufficient for acute cognitive enhancement in this population. The results highlight the need to consider the complex pathophysiology of SCZ and suggest that future research should explore multi-session interventions or distributed network-based stimulation. ClinicalTrials.gov (NCT03872310). Registered on May 1, 2019.