Neuronal Networks Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
Faculty of Veterinary Medicine and Neuroscience Center, University of Helsinki, Helsinki, Finland.
Nat Neurosci. 2018 Dec;21(12):1742-1752. doi: 10.1038/s41593-018-0278-y. Epub 2018 Nov 26.
The mechanism of seizure emergence and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are two of the most important unresolved issues in modern epilepsy research. We found that the transition to seizure is not a sudden phenomenon, but is instead a slow process that is characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon that is observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by synchronous synaptic input from IEDs. IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either anti-seizure or pro-seizure effects. We found that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence.
癫痫发作的发生机制和短暂性癫痫样放电(IEDs)在癫痫发作中的作用是现代癫痫研究中两个最重要的未解决问题。我们发现,癫痫发作的转变不是一个突然的现象,而是一个缓慢的过程,其特征是神经元网络弹性的逐渐丧失。从动力学的角度来看,这种缓慢的转变是由临界缓慢的原则所控制的,这是一种在由动力学状态之间的转变所描述的系统中可以观察到的稳健的自然现象。在癫痫中,这个过程是由 IEDs 的同步突触输入所调节的。IEDs 是外部的扰动,会在缓慢转变过程中产生阶段性的变化,并对产生癫痫发作的网络的动力学产生相反的影响,导致抗癫痫或促癫痫的效果。我们发现,IEDs 的多方面性质是由放电发生时网络的动力学状态所定义的。
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