Modulation of Interhemispheric Synchronization and Cortical Activity in Healthy Subjects by High-Definition Theta-Burst Electrical Stimulation

Abstract

Background: Various forms of theta-burst stimulation (TBS) such as intermittent TBS (iTBS) and continuous TBS (cTBS) have been introduced as novel facilitation/suppression schemes during repetitive transcranial magnetic stimulation (rTMS), demonstrating a better efficacy than conventional paradigms. Herein, we extended the rTMS-TBS schemes to electrical stimulation of high-definition montage (HD-TBS) and investigated its neural effects on the human brain.

Methods: In a within-subject design, fifteen right-handed healthy adults randomly participated in 10 min and 2 mA HD-TBS sessions: unilateral (Uni)-iTBS, bilateral (Bi)-cTBS/iTBS, and sham stimulation over primary motor cortex regions. A 20-channel near-infrared spectroscopy (NIRS) system was covered on the bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal lobe (PL) for observing cerebral hemodynamic responses in the resting-state and during fast finger-tapping tasks at pre-, during, and poststimulation. Interhemispheric correlation coefficient (IHCC) and wavelet phase coherence (WPCO) from resting-state NIRS and concentration of oxyhemoglobin during fast finger-tapping tasks were explored to reflect the symmetry between the two hemispheres and cortical activity, respectively.

Results: The IHCC and WPCO of NIRS data in the SMC region under Bi-cTBS/iTBS showed relatively small values at low-frequency bands III (0.06-0.15 Hz) and IV (0.02-0.06), indicating a significant desynchronization in both time and frequency domains. In addition, the SMC activation induced by fast finger-tapping exercise was significantly greater during Uni-iTBS as well as during and post Bi-cTBS/iTBS sessions.

Conclusions: It appears that a 10 min and 2 mA Bi-cTBS/iTBS applied over two hemispheres within the primary motor cortex region could effectively modulate the interhemispheric synchronization and cortical activation in the SMC of healthy subjects. Our study demonstrated that bilateral HD-TBS approaches is an effective noninvasive brain stimulation scheme which could be a novel therapeutic for inducing effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.

Figure 1

Schematic illustration for experimental design. (a) The experimental setup: subjects sit comfortably on an adjustable chair and worn a 10-20 system electroencephalography (EEG) head cap attached with HD-TBS electrodes and NIRS emitters and receivers; (b) NIRS montage covering bilateral PFC, SMC, and PL and HD-TBS electrodes arrangement; and (c) three phases (pre, during, and post) of each HD-TBS session with resting-state and finger-tapping exercises in each phase.

Figure 2

Data analysis flowchart.

Figure 3

The electric field distribution for the 4 × 1 HD montage generated by HD-Explore™. (a) All four cathodes were valid, (b) one cathode failed, and (c) only one cathode was valid.

Figure 4

Representative resting-state IHCCs in the frequency bands I–IV in the SMC during Bi-cTBS/iTBS stimulation. (a–d) IHCCs from band I to IV, respectively. Solid line (–) and dashed line (--) indicate HbO oscillation in the left and right hemispheres, respectively.

Figure 5

IHCCs in different cortical regions under three HD-TBS protocols. Data: untransformed IHCC mean ± SEM; bands I–IV: 0.7–2.0 Hz, 0.15–0.7 Hz, 0.06–0.15 Hz, and 0.02–0.06 Hz, respectively. ^∗p ≤ 0.05 and ^∗∗p ≤ 0.01 for significance among three phases. ^#p ≤ 0.05 and ^##p ≤ 0.01 for significance among three HD-TBS sessions.

Figure 6

Representative resting-state WPCOs in the bands I–IV in the SMC by Bi-cTBS/iTBS stimulation. The solid line (-) indicates WPCOs of the bands I–V; the dashed and dotted line (-.) shows WPCO of 100 AAFT; the dashed line (--) displays two standard deviations of 100 WPCO of AAFT; vertical dashed lines reveals different divisions of the frequency bands.

Figure 7

WPCOs in different cortical regions under three HD-TBS protocols. Data: untransformed WPCO mean ± SEM; bands I–IV: 0.7–2.0 Hz, 0.15–0.7 Hz, 0.06–0.15 Hz, and 0.02–0.06 Hz, respectively. ^∗p ≤ 0.05 and ^∗∗p ≤ 0.01 for significance among three phases. ^#p ≤ 0.05 and ^##p ≤ 0.01 for significance among three HD-TBS sessions.

Figure 8

(a) Typical hemodynamic responses in the left and right SMC induced by fast finger-tapping exercises and Bi-cTBS/iTBS stimulation. Red and blue plots indicate the fluctuation of HbO and HbR, respectively; vertical lines indicate the start and stop of the tasks. (b) Block average HbO concentration (black bold plots) from block 2 to block 10.

Figure 9

Group average of △HbO_diff (±SEM) in the (a) PFC, (b) SMC, and (c) PL measured in the pre, during, and 10 min poststimulations of the three HD-TBS sessions. ^∗p ≤ 0.05 and ^∗∗p ≤ 0.01 indicate a significant difference among three phases of each HD-TBS session. ^#p ≤ 0.05 and ^##p ≤ 0.01 indicate a significant difference among three HD-TBS sessions in the same phase.