Table_1_Antiepileptic Efficacy and Network Connectivity Modulation of Repetitive Transcranial Magnetic Stimulation by Vertex Suppression.DOCX

A core feature of drug-resistant epilepsy is hyperexcitability in the motor cortex, and low-frequency repetitive transcranial magnetic stimulation (rTMS) is a suitable treatment for seizures. However, the antiepileptic effect causing network reorganization has rarely been studied. Here, we assessed the impact of rTMS on functional network connectivity (FNC) in resting functional networks (RSNs) and their relation to treatment response. Fourteen patients with medically intractable epilepsy received inhibitive rTMS with a figure-of-eight coil over the vertex for 10 days spread across two weeks. We designed a 6-week follow-up phase divided into four time points to investigate FNC and rTMS-induced timing-dependent plasticity, such as seizure frequency and abnormal interictal discharges on electroencephalography (EEG). For psychiatric comorbidities, the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A) were applied to measure depression and anxiety before and after rTMS. FNC was also compared to that of a cohort of 17 healthy control subjects. The after-effects of rTMS included all subjects that achieved the significant decrease rate of more than 50% in interictal epileptiform discharges and seizure frequency, 12 (14) patients with the reduction rate above 50% compared to the baseline, as well as emotional improvements in depression and anxiety (p < 0.05). In the analysis of RSNs, we found a higher synchronization between the sensorimotor network (SMN) and posterior default-mode network (pDMN) in epileptic patients than in healthy controls. In contrast to pre-rTMS, the results demonstrated a weaker FNC between the anterior DMN (aDMN) and SMN after rTMS, while the FNC between the aDMN and dorsal attention network (DAN) was greater (p < 0.05, FDR corrected). Importantly, the depressive score was anticorrelated with the FNC of the aDMN-SMN (r = −0.67, p = 0.0022), which was markedly different in the good and bad response groups treated with rTMS (p = 0.0115). Based on the vertex suppression by rTMS, it is possible to achieve temporary clinical efficacy by modulating network reorganization in the DMN and SMN for patients with refractory epilepsy.

耐药性癫痫的核心特征在于运动皮层的过度兴奋性，而低频重复经颅磁刺激（rTMS）则是治疗癫痫发作的适宜手段。然而，关于rTMS引起的网络重组导致的抗癫痫效果的探讨却鲜有研究。在本研究中，我们对rTMS对静息态功能网络（RSNs）中功能网络连接（FNC）的影响及其与治疗效果的关系进行了评估。十四名患有难治性癫痫的患者在两周内，连续十天接受了经头顶部的八字形线圈抑制性rTMS治疗。我们设计了一个为期六周的随访阶段，分为四个时间点，以研究FNC和rTMS诱导的时间依赖性可塑性，例如癫痫发作频率和脑电图（EEG）上的异常发作间期放电。对于精神疾病共病情况，我们采用了汉密尔顿抑郁量表（HAM-D）和汉密尔顿焦虑量表（HAM-A）在rTMS前后评估抑郁和焦虑。FNC还与17名健康对照者的FNC进行了比较。rTMS的后效应包括所有达到间期癫痫样放电和癫痫发作频率显著降低超过50%的受试者，与基线相比，12名（14名）患者的降低率超过50%，以及抑郁和焦虑情绪的改善（p < 0.05）。在分析RSNs时，我们发现癫痫患者与健康对照组相比，感觉运动网络（SMN）与后默认模式网络（pDMN）之间的同步性更高。与rTMS前相比，结果显示rTMS后前默认模式网络（aDMN）与SMN之间的FNC减弱，而aDMN与背侧注意力网络（DAN）之间的FNC增强（p < 0.05，FDR校正）。值得注意的是，抑郁评分与aDMN-SMN的FNC呈负相关（r = −0.67，p = 0.0022），这在接受rTMS治疗的反应良好和不良组之间有显著差异（p = 0.0115）。基于rTMS引起的顶叶抑制，通过调节DMN和SMN中的网络重组，对于耐药性癫痫患者，有可能实现暂时的临床疗效。