Differing effectiveness of transcranial random noise stimulation and transcranial direct current stimulation for enhancing working memory in healthy individuals: a randomized controlled trial

Background: Transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (DLPFC) is a promising technique for enhancing working memory (WM) performance in healthy and psychiatric populations. However, limited information is available about the effectiveness of transcranial random noise stimulation (tRNS) applied to the left DLPFC on WM. This study investigated the effectiveness of tRNS on WM compared with that of tDCS, which has established functional evidence. Methods: This randomized, double-blind, sham-controlled trial enrolled 120 healthy right-handed adults who were randomly allocated to four stimulation groups: tRNS + direct current (DC) offset, tRNS, tDCS, or sham. Each stimulus was placed over the left DLPFC and had a current intensity of 2 mA applied for 20 min during the dual n-back task. The dual n-back task was repeated thrice: pre-stimulation, during stimulation, and post-stimulation. The d-prime scores, and response times were calculated as the main outcome measures. A linear mixed model was created to identify the main effects and interactions between the groups and times, with the group and time as fixed effects, and baseline performance and the subject as a covariate and random effect, respectively. The relationships between the benefit of each stimulus and baseline WM performance were also examined. Results: For the d-prime score during stimulation, the tRNS group significantly performed better than the sham group at online assessment (β = 0.310, p = 0.001). In the relationships between the benefit of each stimulus and baseline WM performance, the tRNS group had significantly larger negative line slopes than the sham group for the d-prime score (β = −0.233, p = 0.038). Conclusions: tRNS applied to the left DLPFC significantly improved WM performance and generated greater benefits for healthy individuals with lower WM performance. These findings highlight the potential utility of tRNS for enhancing WM performance in individuals with lower WM performance and contribute evidence for clinical application to patients with cognitive decline. Trial Registration: This study was registered in the University Hospital Medical Information Network Clinical Trial Registry in Japan (UMIN000047365) on April 1, 2022; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054021.