Published online Sep 19, 2025. doi: 10.5498/wjp.v15.i9.107754
Revised: May 22, 2025
Accepted: July 24, 2025
Published online: September 19, 2025
Processing time: 150 Days and 23.4 Hours
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.
To conduct a systematic review and meta-analysis evaluating the effects of theta-tACS on working memory performance in healthy adults.
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.
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.
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.
Core Tip: In this meta-analysis, we evaluated theta-band transcranial alternating current stimulation for working memory enhancement in healthy adults. Although initial analyses showed moderate efficacy, correction for publication bias rendered effects nonsignificant. Notably, task-specific effects emerged, specifically showing significant improvement in n-back tasks vs null effects in delayed match-to-sample tasks. Key moderators of performance included stimulation frequency, concurrent status, task modality, and stimulation duration for n-back tasks and the target region for match-to-sample tasks. Although these findings primarily guide cognitive enhancement protocols for healthy individuals, they also provide mechanistic insights for potential clinical translation to populations with working memory deficits.