Bidirectional effects on interhemispheric resting-state functional connectivity induced by excitatory and inhibitory repetitive transcranial magnetic stimulation

Abstract

Several recent studies using functional magnetic resonance imaging (fMRI) have shown that repetitive transcranial magnetic stimulation (rTMS) affects not only brain activity in stimulated regions but also resting-state functional connectivity (RSFC) between the stimulated region and other remote regions. However, these studies have only demonstrated an effect of either excitatory or inhibitory rTMS on RSFC, and have not clearly shown the bidirectional effects of both types of rTMS. Here, we addressed this issue by performing excitatory and inhibitory quadripulse TMS (QPS), which is considered to exert relatively large and long-lasting effects on cortical excitability. We found that excitatory rTMS (QPS with interstimulus intervals of 5 ms) decreased interhemispheric RSFC between bilateral primary motor cortices, whereas inhibitory rTMS (QPS with interstimulus intervals of 50 ms) increased interhemispheric RSFC. The magnitude of these effects on RSFC was significantly correlated with that of rTMS-induced effects on motor evoked potential from the corresponding muscle. The bidirectional effects of QPS were also observed in the stimulation over prefrontal and parietal association areas. These findings provide evidence for the robust bidirectional effects of excitatory and inhibitory rTMSs on RSFC, and raise a possibility that QPS can be a powerful tool to modulate RSFC.

Keywords: QPS; fMRI; rTMS; rs-fcMRI; transcallosal connection.

Figure 1

Experimental procedure. A. rTMS Protocol. Two types of rTMS were used in the present study. The protocol for excitatory rTMS consisted of 360 trains of quadripulse rTMS at 5‐ms interstimulus interval (ISI), whereas that for inhibitory rTMS consisted of 360 trains of quadripulse rTMS at 50 ms ISI. B. Experimental Design. The present overall experimental design consisted of three sessions: the baseline, excitatory and inhibitory rTMS sessions. In the baseline session, the subjects underwent a localizer fMRI scan and a resting‐state fMRI scan. In the two types of rTMS, the subjects were administrated by rTMS ∼10 min before resting‐state fMRI scan. The order of the two rTMS sessions was counter‐balanced across subjects, and the sessions were conducted at an interval longer than 1 week.

Figure 2

Effects of rTMS on MEP. The Y axis shows the ratio of the post‐rTMS MEP of the right FDI to the baseline MEP. In both excitatory and inhibitory rTMS, the expected changes in MEP were observed. Error bar: s.e.m. *: P < 0.05.

Figure 3

Changes in RSFC after rTMS of left M1. A. Statistical maps of functional connectivity with the left M1 in pre‐rTMS sessions (i.e., baseline sessions). B and C. Changes in RSFC with the left M1 induced by excitatory rTMS (panel B) and inhibitory rTMS (panel C). The color scale shown on the right indicates statistical significance level. The blue circles indicate the approximate location of the left M1, which was determined by the functional localizer scan. These panels indicate the subtraction between the functional connectivity maps of the pre‐rTMS and post‐rTMS sessions; as a consequence, the local effects were eliminated. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 4

Changes in inter‐hemispheric RSFC. A. Group effects of rTMS. Excitatory and inhibitory rTMS induced significant decrease and increase in interhemispheric RSFC between the bilateral M1s. ***: P < 0.001 in one‐sample t tests. Error bars: s.e.m. B. Correlation between effects of rTMS on MEP and RSFC. The magnitudes of the effects on inter‐hemispheric RSFC were significantly correlated with the magnitude of the effects on MEP.