Transcranial burst electrical stimulation contributes to neuromodulatory effects in the rat motor cortex

Thi Xuan Dieu Nguyen; Chi-Wei Kuo; Chih-Wei Peng; Hao-Li Liu; Ming-Yuan Chang; Tsung-Hsun Hsieh

doi:10.3389/fnins.2023.1303014

Transcranial burst electrical stimulation contributes to neuromodulatory effects in the rat motor cortex

Front Neurosci. 2023 Dec 11:17:1303014. doi: 10.3389/fnins.2023.1303014. eCollection 2023.

Authors

Thi Xuan Dieu Nguyen¹, Chi-Wei Kuo¹, Chih-Wei Peng², Hao-Li Liu³, Ming-Yuan Chang⁴, Tsung-Hsun Hsieh^{1

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Affiliations

¹ School of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan.
² School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
³ Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan.
⁴ Division of Neurosurgery, Department of Surgery, Min-Sheng General Hospital, Taoyuan, Taiwan.
⁵ Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
⁶ Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Abstract

Background and objective: Transcranial Burst Electrical Stimulation (tBES) is an innovative non-invasive brain stimulation technique that combines direct current (DC) and theta burst stimulation (TBS) for brain neuromodulation. It has been suggested that the tBES protocol may efficiently induce neuroplasticity. However, few studies have systematically tested neuromodulatory effects and underlying neurophysiological mechanisms by manipulating the polarity of DC and TBS patterns. This study aimed to develop the platform and assess neuromodulatory effects and neuronal activity changes following tBES.

Methods: Five groups of rats were exposed to anodal DC combined with intermittent TBS (tBES+), cathodal DC combined with continuous TBS (tBES-), anodal and cathodal transcranial direct current stimulation (tDCS+ and tDCS-), and sham groups. The neuromodulatory effects of each stimulation on motor cortical excitability were analyzed by motor-evoked potentials (MEPs) changes. We also investigated the effects of tBES on both excitatory and inhibitory neural biomarkers. We specifically examined c-Fos and glutamic acid decarboxylase (GAD-65) using immunohistochemistry staining techniques. Additionally, we evaluated the safety of tBES by analyzing glial fibrillary acidic protein (GFAP) expression.

Results: Our findings demonstrated significant impacts of tBES on motor cortical excitability up to 30 min post-stimulation. Specifically, MEPs significantly increased after tBES (+) compared to pre-stimulation (p = 0.026) and sham condition (p = 0.025). Conversely, tBES (-) led to a notable decrease in MEPs relative to baseline (p = 0.04) and sham condition (p = 0.048). Although tBES showed a more favorable neuromodulatory effect than tDCS, statistical analysis revealed no significant differences between these two groups (p > 0.05). Additionally, tBES (+) exhibited a significant activation of excitatory neurons, indicated by increased c-Fos expression (p < 0.05), and a reduction in GAD-65 density (p < 0.05). tBES (-) promoted GAD-65 expression (p < 0.05) while inhibiting c-Fos activation (p < 0.05), suggesting the involvement of cortical inhibition with tBES (-). The expression of GFAP showed no significant difference between tBES and sham conditions (p > 0.05), indicating that tBES did not induce neural injury in the stimulated regions.

Conclusion: Our study indicates that tBES effectively modulates motor cortical excitability. This research significantly contributes to a better understanding of the neuromodulatory effects of tBES, and could provide valuable evidence for its potential clinical applications in treating neurological disorders.

Keywords: motor evoked potential; neuromodulation; neuroplasticity; rats; transcranial burst electrical stimulation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Science and Technology Council (grant NSTC112-2314-B182-022, NSTC112-2321-B002-021, MOST109-2314-B182-029-MY3, and MOST111-2622-B182-002) and Chang Gung Medical Foundation, Taiwan (CMRPD1M0252 and CMRPD1M0701).