High-Frequency rTMS of the Motor Cortex Modulates Cerebellar and Widespread Activity as Revealed by SVM

Abstract

Functional magnetic resonance imaging (fMRI) studies have shown that the effect of repetitive transcranial magnetic stimulation (rTMS) can induce changes in remote brain regions. In the stimulated regions, low-frequency (≤1 Hz) rTMS induces inhibitory effects, while high-frequency (≥5 Hz) stimulation induces excitatory effects. However, these stereotypical effects arising from low- and high-frequency stimulation are based on measurements of motor evoked potentials (MEPs) induced by pulsed stimulation. To test the effects of rTMS on remote brain regions, the current study recruited 31 young healthy adults who participated in three rTMS sessions (10 Hz high frequency, 1 Hz low frequency, and sham) on three separate days. The stimulation target was based on individual fMRI activation in the motor cortex evoked by a finger movement task. Pre- and post-rTMS resting-state fMRI (RS-fMRI) were acquired. Regional homogeneity (ReHo) and degree centrality (DC) were calculated to measure the local and global connectivity, respectively. Compared with the sham session, high-frequency (10 Hz) rTMS significantly increased ReHo and DC in the right cerebellum, while low-frequency (1 Hz) stimulation did not significantly alter ReHo or DC. Then, using a newly developed PAIR support vector machine (SVM) method, we achieved accuracy of 93.18-97.24% by split-half validation for pairwise comparisons between conditions for ReHo or DC. While the univariate analyses suggest that high-frequency rTMS of the left motor cortex could affect distant brain activity in the right cerebellum, the multivariate SVM results suggest that both high- and low-frequency rTMS significantly modulated widespread brain activity. The current findings are useful for increasing the understanding of the mechanisms of rTMS, as well as guiding precise individualized rTMS treatment of movement disorders.

Keywords: cerebellum; fMRI-guided navigation; motor cortex; rTMS; resting-state fMRI.

FIGURE 1

Finger tapping, a block design task with a self-paced rhythm at around 2 s, during a 4-min MRI scan.

FIGURE 2

Three-level (1 Hz/low frequency, 10 Hz/high frequency, and sham) one-way ANOVA on changes in brain activity (post- minus pre-rTMS). The right cerebellum showed significant differences between the three stimulation conditions (GRF correction, single voxel p < 0.001, cluster level p < 0.05).

FIGURE 3

Pairwise paired t tests between stimulation conditions on the ReHo and DC value of the peak voxel of F maps in the right cerebellum. The coordinates of the peak voxels were the same as Table 2. *Still significant after Bonferroni correction of 0.05/15 = 0.0033.

FIGURE 4

Paired t tests between post- and pre-rTMS on ReHo and DC value of the peak voxel of F maps in the right cerebellum. The coordinates of the peak voxels were the same as Table 2. *Still significant after Bonferroni correction of 0.05/15 = 0.0033.

FIGURE 5

Left column: Brain regions that showed different contributions between stimulation conditions identified by ReHo maps within the mask of uncorrected F map of ANOVA. Right column: Paired t tests between stimulation conditions on ReHo maps within the mask of uncorrected F map of ANOVA.

FIGURE 6

Left column: Brain regions that showed different contributions between stimulation conditions identified by DC maps within the mask of uncorrected F map of ANOVA. Right column: Paired t tests between stimulation conditions on DC maps within the mask of uncorrected F map of ANOVA.

FIGURE 7

The area under the curve (AUC) of the receiver operating characteristic (ROC) of the peak voxels of the F maps of ReHo (x = 39, y = -60, z = -54) and DC (x = 42, y = -57, z = -54).