The idea of the epileptic brain being highly excitable and facilitated to synchronic activity has guided pharmacological treatment since the early twentieth century. Although tackling epilepsy's seizure-prone feature, by tonically modifying overall circuit excitability and/or connectivity, the last 50 years of drug development has not seen a substantial improvement in seizure suppression of refractory epilepsies. This review presents a new conceptual framework for epilepsy in which the temporal dynamics of the disease plays a more critical role in both its understanding and therapeutic strategies. The repetitive epileptiform pattern (characteristic during ictal activity) and other well-defined electrographic signatures (i.e., present during the interictal period) are discussed in terms of the sequential activation of the circuit motifs. Lessons learned from the physiological activation of neural circuitry are used to further corroborate the argument and explore the transition from proper function to a state of instability. Furthermore, the review explores how interfering in the temporally dependent abnormal connectivity between circuits may work as a therapeutic approach. We also review the use of probing stimulation to access network connectivity and evaluate its power to determine transitional states of the dynamical system as it moves towards regions of instability, especially when conventional electrographic monitoring is proven inefficient. Unorthodox cases, with little or no scalp electrographic correlate, in which ictogenic circuitry and/or seizure spread is temporally restricted to neurovegetative, cognitive, and motivational areas are shown as possible explanations for sudden death in epilepsy (SUDEP) and other psychiatric comorbidities. In short, this review presents a paradigm shift in the way that we address the disease and is aimed to encourage debate rather than narrow the rationale epilepsy is currently engaged in. This article is part of the Special Issue "NEWroscience 2018".

中文翻译：

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癫痫作为一个动力系统，是癫痫学最需要的范式转变

自 20 世纪初以来，癫痫大脑高度兴奋并促进同步活动的想法一直指导着药物治疗。尽管通过调节整体回路兴奋性和/或连通性来解决癫痫易发作的特征，但过去 50 年的药物开发在难治性癫痫的发作抑制方面并未取得实质性改善。本综述提出了一个新的癫痫概念框架，其中疾病的时间动态在其理解和治疗策略中起着更重要的作用。重复的癫痫样模式（发作活动期间的特征）和其他明确定义的电图特征（即出现在发作间期）根据电路基序的顺序激活进行了讨论。从神经回路的生理激活中吸取的教训被用来进一步证实这一论点，并探索从正常功能到不稳定状态的转变。此外，该评论探讨了如何干扰电路之间的时间依赖性异常连接可能会作为一种治疗方法发挥作用。我们还回顾了使用探测刺激来访问网络连接并评估其在动态系统向不稳定区域移动时确定其过渡状态的能力，特别是当传统的电子图监测被证明效率低下时。非正统病例，很少或没有头皮电图相关性，其中发源性回路和/或癫痫发作在时间上仅限于神经植物、认知、和动机领域被显示为癫痫猝死 (SUDEP) 和其他精神疾病的可能解释。简而言之，这篇综述提出了我们应对疾病的方式的范式转变，旨在鼓励辩论而不是缩小目前癫痫症的基本原理。本文是特刊“NEWroscience 2018”的一部分。