Cognitive and emotional effects of bilateral prefrontal anodal tDCS and high-frequency tRNS in schizophrenia: a randomized sham-controlled study

Abstract Cognitive deficits in schizophrenia significantly hinder functional outcomes and often remain unresponsive to conventional treatments. While initial evidence suggested potential pro-cognitive effects of electrical brain stimulation in schizophrenia, recent meta-analyses have not supported these findings, warranting further investigation on intervention optimization. This sham-controlled crossover study explored cognitive and emotional effects of bilateral dorsolateral prefrontal cortex (DLPFC) anodal transcranial direct current stimulation (tDCS) and high-frequency transcranial random noise stimulation (tRNS) in schizophrenia. Thirty-six male patients with schizophrenia participated in a crossover trial, receiving three sessions (tDCS, tRNS, sham) in counterbalanced order with 1-week intervals. tDCS and tRNS sessions involved 20-min 2 mA anodal stimulation and 2 mA 100–640 Hz random noise stimulation targeting the left and right DLPFCs (F3–F4) with two extracephalic return electrodes. Executive functions (working memory, spatial planning) were assessed during stimulation, and emotional changes were measured with the Positive and Negative Affect Schedule (PANAS) pre- and post-stimulation. Additionally, side effects and blinding efficacy were evaluated. Both bilateral DLPFC anodal tDCS and high-frequency tRNS significantly improved planning performance (mean problems solved, mean number of moves) compared to sham, with tRNS additionally enhancing working memory accuracy and strategy score. Both interventions increased positive affect and reduced negative affect after the intervention, with tRNS showing greater enhancement of positive emotions. Reduced negative affect tRNS was correlated with improved executive planning. Side effects were minimal, and blinding was effective for the sham condition. Bilateral DLPFC anodal tDCS and high-frequency tRNS show promise as adjunctive treatments for schizophrenia, especially for cognitive deficits, with broader cognitive and emotional benefits observed with tRNS. ClinicalTrials.gov Identifier: NCT06155786 https://clinicaltrials.gov/study/NCT06155786 .