Understanding state-dependent and metaplastic mechanisms in cognitive neurostimulation: a systematic review of transcranial electrical stimulation (tES) protocols

Transcranial electrical stimulation (tES) has been widely investigated for cognitive enhancement and neurorehabilitation; however, its cognitive effects remain highly variable across studies and individuals. Increasing evidence suggests that this variability may be explained by state-dependent and history-dependent plasticity mechanisms rather than stimulation parameters alone. This systematic review aimed to synthesize experimental human studies investigating how stimulation protocols interact with brain state, baseline performance, and prior stimulation history to influence cognitive outcomes. Following PRISMA 2020 guidelines, systematic searches were conducted in PubMed, Scopus, and Web of Science, resulting in 27 eligible experimental studies published between 2008 and 2024. Across cognitive domains such as working memory, declarative memory, perceptual learning, inhibitory control, and creativity, stimulation effects were consistently modulated by baseline performance, task engagement, emotional or physiological state, stimulation timing, and prior stimulation exposure. These findings suggest that transcranial electrical stimulation may be better conceptualized as a state-dependent modulator of neural plasticity rather than a direct cognitive enhancement technique. Overall, the review indicates that protocol-dependent factors such as timing, priming, baseline state, and stimulation history play a critical role in shaping cognitive outcomes. Future research should therefore prioritize state-dependent, task-coupled, and individualized stimulation protocols to improve reproducibility and to better understand variability in cognitive and clinical outcomes.
This work was partially conducted at the Psychology Research Centre (CIPsi; PSI/01662), School of Psychology, University of Minho. The Centre is registered under the DOI: https://doi.org/ 10.54499/UID/01662/2025 (accessed on 19 December 2025).