Effect of theta-transcranial alternating current stimulation on working memory performance among healthy adults: A systematic review and meta-analysis.

Background: Working memory serves as a fundamental cognitive function that substantially impacts performance in various cognitive tasks. Extensive neurophysiological research has established that theta oscillations (4-8 Hz) play an essential role in supporting working memory operations. Theta-band transcranial alternating current stimulation (tACS) offers a potential mechanism for working memory enhancement through direct modulation of these fundamental neural oscillations. Nevertheless, current empirical evidence shows substantial variability in the observed effects of theta-tACS across studies.

Aim: To conduct a systematic review and meta-analysis evaluating the effects of theta-tACS on working memory performance in healthy adults.

Methods: A systematic literature search was performed on PubMed, EMBASE, and Web of Science up to March 10, 2025. Effect sizes were computed using Hedges' g with 95% confidence intervals (CIs), with separate meta-analyses for all included studies and for distinct working memory paradigms [n-back and delayed match-to-sample (DMTS) tasks] to examine potential task-specific effects. Subgroup analyses and meta-regression were performed to evaluate the influence of key moderating variables.

Results: The systematic review included 21 studies (67 effect sizes). Initial meta-analysis showed theta-tACS moderately improved working memory (Hedges' g = 0.405, 95%CI: 0.212-0.598). However, this effect became nonsignificant after correcting for publication bias (trim-and-fill adjusted Hedges' g = 0.082, 95%CI: -0.052 to 0.217). Task-specific analyses revealed significant benefits in n-back tasks (Hedges' g = 0.463, 95%CI: 0.193-0.733) but not in DMTS tasks (Hedges' g = 0.257, 95%CI: -0.186 to 0.553). Moderator analyses showed that performance in n-back tasks was influenced by stimulation frequency (P = 0.001), concurrent status (P = 0.014), task modality (P = 0.005), and duration (P = 0.013), whereas only the region of targeted stimulation (P = 0.012) moderated DMTS tasks.

Conclusion: Theta-tACS enhances working memory in healthy adults, with effects modulated by the task type and protocol parameters, offering dual implications for cognitive enhancement and clinical interventions.