Multifocal transcranial electrical stimulation to enhance cognitive functions: a systematic review.

Background: Multifocal transcranial Electrical Stimulation (tES) has emerged as an innovative approach for modulating cognitive functions by concurrently targeting multiple brain regions. Despite its potential, the efficacy and underlying mechanisms of this technique remain unclear. Objective: To evaluate the efficacy of multifocal tES in enhancing cognitive function by examining targeted brain regions, stimulation protocols, and behavioral and neurophysiological outcomes. Methods: A systematic search of PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science databases was conducted up to February 10, 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The inclusion criteria encompassed human studies utilizing concurrent dual-site or multifocal tES with pre- and post-intervention behavioral assessments. Studies on deep brain stimulation, corticocortical paired associative stimulation, sequential stimulation, case reports, and reviews were excluded. Results: Of the 1,453 initial records, 14 met the inclusion criteria. The studies predominantly employed transcranial direct current stimulation/transcranial alternating current stimulation, targeting the frontoparietal network. Neurophysiological data from electroencephalography and functional magnetic resonance imaging revealed network-level modulations. Behavioral outcomes were inconsistent, with some studies reporting improvements in executive function, working memory, and response inhibition, whereas others showed no significant advantages over sham stimulation. Conclusion: Although multifocal tES is a promising modality, clearly determining its efficacy is currently limited by heterogeneous study designs, small sample sizes, and conflicting findings. Future research should prioritize multi-arm trials, incorporate neurophysiological biomarkers, and develop personalized stimulation protocols to optimize the effectiveness of this technique. Trial registration: PROSPERO Registration # CRD420250646196.