University of Rennes, Inserm-U1099, LTSI, Rennes, France.
Aix Marseille University, Inserm, INS, Institut de Neurosciences des Systèmes, Marseille, France.
PLoS Comput Biol. 2020 Nov 9;16(11):e1008430. doi: 10.1371/journal.pcbi.1008430. eCollection 2020 Nov.
Epilepsy is a dynamic and complex neurological disease affecting about 1% of the worldwide population, among which 30% of the patients are drug-resistant. Epilepsy is characterized by recurrent episodes of paroxysmal neural discharges (the so-called seizures), which manifest themselves through a large-amplitude rhythmic activity observed in depth-EEG recordings, in particular in local field potentials (LFPs). The signature characterizing the transition to seizures involves complex oscillatory patterns, which could serve as a marker to prevent seizure initiation by triggering appropriate therapeutic neurostimulation methods. To investigate such protocols, neurophysiological lumped-parameter models at the mesoscopic scale, namely neural mass models, are powerful tools that not only mimic the LFP signals but also give insights on the neural mechanisms related to different stages of seizures. Here, we analyze the multiple time-scale dynamics of a neural mass model and explain the underlying structure of the complex oscillations observed before seizure initiation. We investigate population-specific effects of the stimulation and the dependence of stimulation parameters on synaptic timescales. In particular, we show that intermediate stimulation frequencies (>20 Hz) can abort seizures if the timescale difference is pronounced. Those results have the potential in the design of therapeutic brain stimulation protocols based on the neurophysiological properties of tissue.
癫痫是一种影响全球约 1%人口的动态且复杂的神经系统疾病,其中 30%的患者对药物有抗药性。癫痫的特征是反复发作的阵发性神经放电(所谓的癫痫发作),这些放电通过深度脑电图记录中观察到的大振幅节律性活动表现出来,特别是在局部场电位 (LFPs) 中。标志着向癫痫发作转变的特征涉及复杂的振荡模式,这些模式可以作为一种标记物,通过触发适当的治疗性神经刺激方法来预防癫痫发作的开始。为了研究这些方案,介观尺度上的神经生理集中参数模型,即神经质量模型,是强大的工具,不仅可以模拟 LFP 信号,还可以深入了解与癫痫发作不同阶段相关的神经机制。在这里,我们分析了神经质量模型的多时间尺度动力学,并解释了在癫痫发作前观察到的复杂振荡的潜在结构。我们研究了刺激的群体特异性效应以及刺激参数对突触时间尺度的依赖性。特别是,我们表明,如果时间尺度差异明显,中间刺激频率(>20 Hz)可以中止癫痫发作。这些结果有可能基于组织的神经生理特性设计治疗性脑刺激方案。