Neurophysiology Department, GHU Paris Psychiatrie et Neurosciences, Sainte-Anne Hospital, Paris, France.
Université de Paris, Paris, France.
Brain Connect. 2020 Dec;10(10):566-577. doi: 10.1089/brain.2020.0798. Epub 2020 Nov 18.
VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiseizure effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractory epilepsy treated by vagus nerve stimulation (VNS), between VNS-stimulated "ON" and nonstimulated "OFF" periods and between responder (R) and nonresponder (NR) patients. Scalp-EEG was performed for 35 patients treated by VNS, using 21 channels and 2 additional electrodes on the neck to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of ∼50% was documented. We analyzed the synchronization in EEG time series during "ON" and "OFF" periods of stimulation, using average phase lag index (PLI) in signal space and phase-locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and nonresponder patients. Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were R and 15 were NR. For responder patients, PLI during ON periods was significantly lower than that during OFF periods in delta ( = 0.009), theta ( = 0.02), and beta ( = 0.04) frequency bands. For nonresponder patients, there were no significant differences between ON and OFF periods. Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta ( = 0.02), theta ( = 0.04), and beta ( = 0.03) frequency bands. Our results were confirmed using PLV in theta band ( < 0.05). No significant differences in MST were observed between R and NR patients. The correlation between VNS-induced interictal EEG time-series desynchronization and decrease in seizure frequency suggested that VNS therapeutic impact might be related to changes in interictal functional connectivity. Impact statement Electroencephalography (EEG) desynchronization has been proposed to be a mechanism for antiepileptic effect of vagus nerve stimulation (VNS). We measured interictal EEG time-series synchronization during stimulated (ON) and nonstimulated (OFF) periods in epileptic patients treated by VNS. Phase lag index differences between ON and OFF periods were measured in delta, theta, and beta bands only in responder patients. To our knowledge, our study is the first to statistically correlate interictal cortical desynchronization during ON periods with reduction in seizure frequency. Our result supports the hypothesis that the antiseizure effect of VNS is mediated by cortical desynchronization.
迷走神经刺激（VNS）是一种治疗药物难治性癫痫的辅助神经调节疗法。VNS 的抗癫痫作用被认为与功能连接的弥散调节有关，但仍有待证实。
为了研究迷走神经刺激（VNS）治疗的药物难治性癫痫患者的脑电图（EEG）功能连接指标，在 VNS 刺激的“ON”和非刺激的“OFF”期间以及应答者（R）和非应答者（NR）患者之间。对 35 例接受 VNS 治疗的患者进行头皮 EEG 检查，使用 21 个通道和颈部的另外 2 个电极来检测 VNS 刺激。如果记录到癫痫发作频率降低约 50%，则将患者定义为 VNS 应答者。我们使用信号空间中的平均相位滞后指数（PLI）和 10 个源之间的锁相值（PLV）分析了刺激“ON”和“OFF”期间的 EEG 时间序列中的同步性。基于图论，我们计算了脑网络模型，并分析了应答者和非应答者患者的最小生成树（MST）。
在接受 VNS 治疗中位数为 7 年（4 个月至 22 年）的 35 例患者中，20 例为 R，15 例为 NR。对于应答者患者，ON 期间的 PLI 明显低于 OFF 期间的 PLI（Delta = 0.009，Theta = 0.02，Beta = 0.04）。对于非应答者患者，ON 和 OFF 期间没有显著差异。此外，癫痫发作频率的变化与 Delta（= 0.02）、Theta（= 0.04）和 Beta（= 0.03）频带中的 PLI OFF/ON 比值相关。我们的结果在Theta 频段使用 PLV 得到了证实（<0.05）。R 和 NR 患者之间没有观察到 MST 的显著差异。
VNS 诱导的间发性 EEG 时间序列去同步与癫痫发作频率降低之间的相关性表明，VNS 的治疗效果可能与间发性功能连接的变化有关。
声明
脑电图（EEG）去同步已被提出是迷走神经刺激（VNS）抗癫痫作用的机制。我们测量了接受 VNS 治疗的癫痫患者在刺激（ON）和非刺激（OFF）期间的间发性 EEG 时间序列同步性。仅在应答者患者中测量了 ON 和 OFF 期间的 Delta、Theta 和 Beta 频段的相位滞后指数差异。据我们所知，我们的研究首次在统计学上关联了 ON 期间的皮质间去同步与癫痫发作频率的降低。我们的结果支持这样的假设，即 VNS 的抗癫痫作用是通过皮质去同步介导的。
