Sherdil Ariana, Chabardès Stephan, David Olivier, Piallat Brigitte
Inserm, U1216, Grenoble, F-38000, France; Univ Grenoble Alpes, Grenoble, F-38000, France.
Inserm, U1216, Grenoble, F-38000, France; Univ Grenoble Alpes, Grenoble, F-38000, France; CHU Grenoble Alpes, Department of Neurosurgery, Grenoble, F-38000, France; Clinatec, Research Centre Edmond Safra, CEA-LETI, Grenoble, F-38000, France.
Brain Stimul. 2020 Nov-Dec;13(6):1678-1686. doi: 10.1016/j.brs.2020.09.026. Epub 2020 Oct 6.
Although the mechanisms by which deep brain stimulation (DBS) modifies the activity of the ictal network are mostly undefined, recent studies have suggested that DBS of the anterior nucleus of the thalamus (ANT) can be an effective treatment for mesial temporal lobe epilepsy (MTLE) when resective surgery cannot be performed. In a nonhuman primate (NHP) model of MTL seizures, we showed that the ANT was actively involved during interictal and ictal periods through different patterns and that the hippocampus (HPC) and ANT synchronously oscillate in the high beta-band during seizures.
Based on those findings, we evaluated whether the frequency of stimulation is an important parameter that interferes with seizures and how to adapt stimulation protocols to it.
We investigated the effects of low-frequency (40 Hz - determined as the ictal frequency of correlation between structures) and high-frequency (130 Hz - as commonly used in clinic) ANT stimulation in three monkeys in which MTLE seizures were initiated.
Low-frequency stimulation had a strong effect on the number of seizures and the total time spent in seizure, whereas high-frequency stimulation had no effect. The coherence of oscillations between the HPC and the ANT was significantly correlated with the success of low-frequency stimulation: the greater the coherence was, the greater the antiepileptic effect of ANT-DBS.
Our results suggest that low-frequency stimulation is efficient in treating seizures in a nonhuman primate model. More importantly, the study of the coherence between the ANT and HPC during seizures can help to predict the anti-epileptic effects of ANT stimulation. Furthermore, the DBS paradigm could be customized in frequency for each patient on the basis of the coherence spectral pattern.
尽管深部脑刺激(DBS)改变发作期网络活动的机制大多尚不明确,但最近的研究表明,当无法进行切除性手术时,丘脑前核(ANT)的DBS可作为内侧颞叶癫痫(MTLE)的有效治疗方法。在MTL癫痫的非人灵长类动物(NHP)模型中,我们发现ANT在发作间期和发作期通过不同模式积极参与其中,并且海马体(HPC)和ANT在发作期间在高β波段同步振荡。
基于这些发现,我们评估了刺激频率是否是干扰癫痫发作的重要参数,以及如何据此调整刺激方案。
我们在三只引发MTLE癫痫的猴子中研究了低频(40Hz - 确定为结构间发作期相关性频率)和高频(130Hz - 临床常用)ANT刺激的效果。
低频刺激对癫痫发作次数和发作总时长有显著影响,而高频刺激则无影响。HPC和ANT之间振荡的相干性与低频刺激的成功率显著相关:相干性越大,ANT-DBS的抗癫痫效果越好。
我们的结果表明,低频刺激在非人灵长类动物模型中治疗癫痫发作是有效的。更重要的是,研究发作期间ANT和HPC之间的相干性有助于预测ANT刺激的抗癫痫效果。此外,可根据相干频谱模式为每位患者定制频率不同的DBS方案。