Syncing the brain's networks: dynamic functional connectivity shifts from temporal interference

Abstract

Background: Temporal interference (TI) stimulation, an innovative non-invasive brain stimulation approach, has the potential to activate neurons in deep brain regions. However, the dynamic mechanisms underlying its neuromodulatory effects are not fully understood. This study aims to investigate the effects of TI stimulation on dynamic functional connectivity (dFC) in the motor cortex.

Methods: 40 healthy adults underwent both TI and tDCS in a double-blind, randomized crossover design, with sessions separated by at least 48 h. The total stimulation intensity of TI is 4 mA, with each channel's intensity set at 2 mA and a 20 Hz frequency difference (2 kHz and 2.02 kHz). The tDCS stimulation intensity is 2 mA. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected before, during, and after stimulation. dFC was calculated using the left primary motor cortex (M1) as the region of interest (ROI) and analyzed using a sliding time-window method. A two-way repeated measures ANOVA (group × time) was conducted to evaluate the effects of TI and tDCS on changes in dFC.

Results: For CV of dFC, significant main effects of stimulation type (P = 0.004) and time (P < 0.001) were observed. TI showed lower CV of dFC than tDCS in the left postcentral gyrus (P < 0.001). TI-T2 displayed lower CV of dFC than TI-T1 in the left precentral gyrus (P < 0.001). For mean dFC, a significant main effect of time was found (P < 0.001). TI-T2 showed higher mean dFC than tDCS-T2 in the left postcentral gyrus (P = 0.018). Within-group comparisons revealed significant differences between time points in both TI and tDCS groups, primarily in the left precentral and postcentral gyri (all P < 0.001). Results were consistent across different window sizes.

Conclusion: 20 Hz TI stimulation altered dFC in the primary motor cortex, leading to a significant decreasing variability and increasing mean connectivity strength in dFC. This outcome indicates that the 20 Hz TI frequency interacted with the motor cortex's natural resonance.

Keywords: dynamic functional connectivity; non-invasive brain stimulation; primary motor cortex; resting-state fMRI; temporal interference.

FIGURE 1

Experimental protocol. (A) Assignment of participants to one of the experimental groups. (B) Timeline of the procedures accomplished before, during and after the tES-MRI protocol. TI, temporal interference stimulation; tDCS, transcranial direct current stimulation.

FIGURE 2

(A) Simulation head model with electrode placements. (B) Spatial configuration of stimulation electrodes. Blue electrodes: cathode, 2000 Hz channel; red electrodes: anode, 2020 Hz channel. White circle indicates the hot spot.

FIGURE 3

(A) Simulation head model with electrodes. The blue electrode is the cathode, and the red electrode is the anode. (B) Location of stimulation electrodes. Based on the international 10–20 system, anodal (C3), cathodal (T7, P3, Cz). (C) Simulated electrical field. P: Posterior, A: anterior. The color bar is the intensity of stimulation.

FIGURE 4

Significant differences in brain regions for the CV of dFC between tDCS-T2 and TI-T2. Compared with tDCS-T2, TI-T2 showed significantly increased CV of dFC (voxel p < 0.005, cluster p < 0 .05, cluster-level FDR corrected, cluster size ≥ 31 voxels). The color bar indicates the t-value. CV, Coefficient of Variation; T2, during stimulation phase; A, anterior; L, left; P, posterior.

FIGURE 5

Significant differences in brain regions for the CV of dFC between TI-T1 and TI-T2. Compared with TI-T1 group, TI-T2 showed significantly increased CV of dFC (voxel p < 0.005, cluster p < 0 .05, cluster-level FDR corrected, cluster size ≥ 91 voxels). The color bar indicates the t-value. CV: Coefficient of Variation; T1, baseline phase; T2, during stimulation phase; A, anterior; L, left; P, posterior.

FIGURE 6

Significant differences in brain regions for mean of dFC between tDCS-T2 and TI-T2. Compared with tDCS-T2, TI-T2 showed significantly increased mean of dFC (cluster p < 0 .05, cluster-level FDR corrected, cluster size ≥ 84 voxels). The color bar indicates the t-value. T2, during stimulation phase; A, anterior; L, left; P, posterior.

FIGURE 7

Significant differences in brain regions for mean of dFC within the TI group. (A) Brain regions with significant difference in mean of dFC between TI-T2 and TI-T1. Compared with TI-T1 group, TI-T2 group showed significantly increased mean of dFC. (B) Brain regions with significant difference in mean of dFC between TI-T3 and TI-T1. Compared with TI-T1, TI-T3 showed significantly increased mean of dFC. (C) Brain regions with significant difference in mean of dFC between TI-T2 and TI-T3. Compared with TI-T3, TI-T2 showed significantly increased mean of dFC. The color bar indicates the t-value. T1, baseline phase; T2, during stimulation phase; T3, post stimulation phase; A, anterior; L, left; P, posterior.

FIGURE 8

Significant differences in brain regions for mean of dFC within the tDCS group. (A) Brain regions with significant difference in mean of dFC between tDCS-T2 and tDCS-T1. Compared with tDCS-T1, tDCS-T1 showed significantly increased mean of dFC. (B) Brain regions with significant difference in mean of dFC between tDCS-T2 and tDCS-T3. Compared with tDCS-T3, tDCS-T2 showed significantly increased mean of dFC. The color bar indicates the t-value. T1, the baseline phase; T2, during stimulation phase; T3, post stimulation phase; A, anterior; L, left; P, posterior.