Department of Neurology, 4BRAIN Research Group, Ghent University Hospital, Ghent, Belgium.
Department of Neurology, 4BRAIN Research Group, Ghent University Hospital, Ghent, Belgium.
Neuromodulation. 2022 Apr;25(3):395-406. doi: 10.1111/ner.13488. Epub 2021 Jul 20.
OBJECTIVES: As a potential treatment for epilepsy, transcutaneous auricular vagus nerve stimulation (taVNS) has yielded inconsistent results. Combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) can be used to investigate the effect of interventions on cortical excitability by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of taVNS on cortical excitability with TMS-EMG and TMS-EEG. These findings are expected to provide insight in the mechanism of action and help identify more optimal stimulation paradigms. MATERIALS AND METHODS: In this prospective single-blind cross-over study, 15 healthy male subjects underwent active and sham taVNS for 60 min, using a maximum tolerated stimulation current. Single and paired pulse TMS was delivered over the right-sided motor hotspot to evaluate MEPs and TEPs before and after the intervention. MEP statistical analysis was conducted with a two-way repeated measures ANOVA. TEPs were analyzed with a cluster-based permutation analysis. Linear regression analysis was implemented to investigate an association with stimulation current. RESULTS: MEP and TEP measurements were not affected by taVNS in this study. An association was found between taVNS stimulation current and MEP outcome measures indicating a decrease in cortical excitability in participants who tolerated higher taVNS currents. A subanalysis of participants (n = 8) who tolerated a taVNS current ≥2.5 mA showed a significant increase in the resting motor threshold, decrease in MEP amplitude and modulation of the P60 and P180 TEP components. CONCLUSIONS: taVNS did not affect cortical excitability measurements in the overall population in this study. However, taVNS has the potential to modulate specific markers of cortical excitability in participants who tolerate higher stimulation levels. These findings indicate the need for adequate stimulation protocols based on the recording of objective outcome parameters.
目的：经皮耳迷走神经刺激（taVNS）作为一种潜在的癫痫治疗方法，其疗效结果并不一致。使用肌电图（TMS-EMG）和脑电图（TMS-EEG）结合经颅磁刺激（TMS），可以通过评估运动诱发电位（MEPs）和 TMS 诱发电位（TEPs）的变化来研究干预对皮质兴奋性的影响。本研究旨在使用 TMS-EMG 和 TMS-EEG 客观评估 taVNS 对皮质兴奋性的影响。这些发现有望深入了解其作用机制，并帮助确定更优化的刺激方案。
材料与方法：在这项前瞻性单盲交叉研究中，15 名健康男性受试者接受了 60 分钟的主动 taVNS 和假 taVNS 治疗，使用可耐受的最大刺激电流。在干预前后，通过单次和双脉冲 TMS 刺激右侧运动热点区，评估 MEPs 和 TEPs。采用双向重复测量方差分析进行 MEP 统计分析。采用基于聚类的置换分析进行 TEP 分析。采用线性回归分析来探讨与刺激电流的相关性。
结果：在本研究中，taVNS 未影响 MEPs 和 TEPs 的测量结果。taVNS 刺激电流与 MEP 结果指标之间存在关联，表明在耐受更高 taVNS 电流的参与者中皮质兴奋性降低。对耐受 taVNS 电流≥2.5 mA 的参与者（n=8）进行的亚组分析显示，静息运动阈值升高，MEP 幅度降低，P60 和 P180 TEP 成分的调制。
结论：在本研究中，taVNS 并未影响总体人群的皮质兴奋性测量结果。然而，taVNS 有可能调节在耐受更高刺激水平的参与者中特定的皮质兴奋性标志物。这些发现表明需要根据客观结果参数的记录来制定适当的刺激方案。
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