Intermittent Theta-Burst Stimulation Reverses the After-Effects of Contralateral Virtual Lesion on the Suprahyoid Muscle Cortex: Evidence From Dynamic Functional Connectivity Analysis

Abstract

Contralateral intermittent theta burst stimulation (iTBS) can potentially improve swallowing disorders with unilateral lesion of the swallowing cortex. However, the after-effects of iTBS on brain excitability remain largely unknown. Here, we investigated the alterations of temporal dynamics of inter-regional connectivity induced by iTBS following continuous TBS (cTBS) in the contralateral suprahyoid muscle cortex. A total of 20 right-handed healthy subjects underwent cTBS over the left suprahyoid muscle motor cortex and then immediately afterward, iTBS was applied to the contralateral homologous area. All of the subjects underwent resting-state functional magnetic resonance imaging (Rs-fMRI) pre- and post-TBS implemented on a different day. We compared the static and dynamic functional connectivity (FC) between the post-TBS and the baseline. The whole-cortical time series and a sliding-window correlation approach were used to quantify the dynamic characteristics of FC. Compared with the baseline, for static FC measurement, increased FC was found in the precuneus (BA 19), left fusiform gyrus (BA 37), and right pre/post-central gyrus (BA 4/3), and decreased FC was observed in the posterior cingulate gyrus (PCC) (BA 29) and left inferior parietal lobule (BA 39). However, in the dynamic FC analysis, post-TBS showed reduced FC in the left angular and PCC in the early windows, and in the following windows, increased FC in multiple cortical areas including bilateral pre- and postcentral gyri and paracentral lobule and non-sensorimotor areas including the prefrontal, temporal and occipital gyrus, and brain stem. Our results indicate that iTBS reverses the aftereffects induced by cTBS on the contralateral suprahyoid muscle cortex. Dynamic FC analysis displayed a different pattern of alteration compared with the static FC approach in brain excitability induced by TBS. Our results provide novel evidence for us in understanding the topographical and temporal aftereffects linked to brain excitability induced by different TBS protocols and might be valuable information for their application in the rehabilitation of deglutition.

Keywords: dynamic functional connectivity analysis; magnetic resonance imaging; repetitive transcranial magnetic stimulation; swallowing; theta-burst stimulation.

FIGURE 1

Schematic of the experimental design. Resting-state functional MRI (Rs-fMRI) was acquired before and after theta burst stimulation (TBS) on the different day. In TBS stimulation, each subject received continuous TBS (cTBS) first on the left suprahyoid muscle cortex and immediately followed intermittent TBS (iTBS) on the right homologous area. The target area for TBS stimulation was guided by neuronavigation.

FIGURE 2

Regional distribution of altered functional connectivity between post-theta-burst stimulation and baseline in healthy subjects. Short-term of aftereffects on brain functional connectivity (FC) induced by intermittent theta burst stimulation (iTBS) followed the contralateral continuous theta burst stimulation (cTBS) (i.e. “virtual lesion”) over the suprahyoid muscle cortex. The upper images represent static FC (A) and a serial of dynamic FC maps (B–H). Lateral, dorsal, medial, basal and posterior views are shown in every figure. Color bar indicates the T-value at the bottom. Areas color-coded in red (blue) indicate the regions in which the values of FC corresponding to post-TBS were higher (lower) than those of pre-TBS (p < 0.05, AlphaSim correction was performed to correct for multiple comparisons). Surface visualization of regions with abnormal FCs using BrainNet Viewer (http://www.nitrc.org/projects/bnv/). For static FC comparison (A), increased FC was found in the precuneus, left fusiform gyrus, and right pre/post-central gyrus, and decreased FC was observed in posterior cingulate gyrus (PCC) and left inferior parietal lobule. In dynamic FC analysis, post-TBS showed reduced FC in left angular and PCC on the early windows (B,C), in the following windows (D–H), increased FC in multiple cortical areas including bilateral pre- and postcentral gyri and paracentral lobule, and non-sensorimotor areas including a body of prefrontal, temporal and occipital gyrus, and brain stem. The details are presented in Table 1.