Understanding Metaplasticity in Cognitive Neurostimulation: A Systematic Review of Transcranial Electrical Stimulation (tES) Protocols

Transcranial electrical stimulation (tES) has become an increasingly prominent tool in cognitive enhancement and neurorehabilitation research, yet its effects remain markedly variable across studies and individuals. A growing body of evidence suggests that this variability reflects metaplasticity, that is, the state-, timing-, and history-dependent regulation of synaptic plasticity, rather than differences in stimulation delivery alone. This systematic review synthesizes human experimental evidence examining how proto-col-specific features of tES shape cognitive outcomes through metaplasticity-related mechanisms. Following PRISMA 2020 guidelines, comprehensive searches of PubMed, Scopus, and Web of Science identified 14 eligible studies published between 2008 and 2024. Most studies employed transcranial direct current stimulation (tDCS), with a smaller number investigating transcranial random noise stimulation (tRNS); notably, no studies using transcranial alternating current stimulation (tACS) met inclusion criteria, despite its strong theoretical relevance to metaplasticity. Across studies, metaplasticity was probed through priming paradigms, manipulations of stimulation timing (online vs. offline or task-locked), polarity sequencing, repeated stimulation sessions, or physiological mod-ulation. Cognitive effects spanning working memory, declarative memory, perceptual learning, inhibitory control, and creativity were consistently shaped by brain state at the time of stimulation, prior neural activity, stimulation history, and individual baseline performance. Identical stimulation parameters frequently yielded facilitatory, null, or even detrimental effects depending on contextual and temporal factors. Beneficial out-comes were most reliably observed when stimulation was temporally aligned with task-relevant neural activity and preceded by appropriate cognitive, emotional, or physiological priming, whereas poorly timed stimulation could disrupt longer-term consolidation. Taken together, these findings indicate that tES operates as a state-sensitive modulator of ongoing plasticity rather than as a uniform cognitive enhancer, underscoring the importance of metaplasticity-informed, task-coupled, and individualized stimulation protocols, as well as the need for future work to more systematically investigate the roles of tACS and tRNS in human cognitive neuroplasticity.