Temporal Interference Stimulation Boosts Working Memory Performance in the Frontoparietal Network

Temporal interference (TI) stimulation is a novel neuromodulation technique that overcomes the depth limitations of traditional transcranial electrical stimulation while avoiding the invasiveness of deep brain stimulation. Our previous behavioral research has demonstrated the effects of multi-target TI stimulation in enhancing working memory (WM) performance, however, the neural mechanisms of this special form of envelope modulation remain unclear. To address this issue, here we designed this randomized, double-blind, crossover study, which consisted of a task-based functional magnetic resonance imaging (fMRI) experiment, to explore how offline TI stimulation modulated brain activity and behavioral performance in healthy adults. We conducted a 2 × 2 within-subjects design with two factors: stimulation (TI vs. Sham) and time (pre vs. post). Participants received two stimulation protocols in a random order: TI (beat frequency: 6 Hz, targeting middle frontal gyrus [MFG] and inferior parietal lobule [IPL]) and sham stimulation. Neuroimaging data of a WM task with different cognitive loads were acquisited immediately before and after stimulation. We found TI stimulation significantly improved d' in the high-demand WM task. Whole-brain analysis showed the significant time-by-stimulation interactions in two main clusters in IPL and precuneus with lower activation after TI stimulation. The generalized psychophysiological interaction (gPPI) analysis revealed a significant interaction in task-modulated connectivity between MFG and IPL, with improvement observed after TI stimulation. Notably, this increasing functional connectivity induced by TI stimulation was positively correlated with better behavioral performance. Overall, our findings show specific effects of TI stimulation on brain activation and functional connectivity in the frontoparietal network and may contribute to provide new perspectives for future neuromodulation applications.