Assessing the neuronal network activity underlying human epileptic seizures

癫痫是第二常见的神经系统疾病。在目前的治疗下，所有患者中有四分之一的患者没有癫痫发作。因此，开发更有效的治疗方法，包括新的抗惊厥药物是很重要的。为了指导这些发展，有必要更好地了解癫痫发作的病理生理，不仅在单细胞水平上，而且在大型神经网络的规模上。是否有可能识别在癫痫发作、癫痫传播和癫痫终止的不同阶段特别活跃的神经网络局部部分？2. 癫痫发作、癫痫传播和癫痫终止是否与全球网络活动的特征变化有关？方法脑电图（EEG）是唯一一种在高时间分辨率下评估人类癫痫发作的神经网络活动的方法。我们将通过最初应用于物理的方法来研究脑电图信号的相互依赖性，该方法用于由大量相互作用元素组成的复杂系统。具体来说，为了识别在不同发作阶段可能至关重要的神经网络局部部分，动态形成的结构将由簇和枢纽的互补数学概念来表征。全局网络活动将通过线性和非线性方法进行分析，这些方法考虑到由于神经元活动的传播延迟而产生的有限时滞的影响。作为一个中心方法学点，研究结果将不断从临床神经生理学的角度进行解释。因此，可以对这些方法的实际效用进行评估，这将影响它们的进一步发展。如果有可能确定，神经网络的哪些部分和全球网络活动的哪些方面与不同的癫痫发作阶段有关，那么合理开发新疗法可能旨在专门改变癫痫大脑的这些空间或动态特征。

ContextEpilepsy is the second most frequent neurological disease. One fourth of all patients do not become seizure-free under current treatment. Therefore it is important to develop more efficient therapies, including new anti-convulsive drugs. To guide these developments, it is necessary to better understand the pathophysiology of epileptic seizures not only on the single-cell level, but also on the scale of large neuronal networks.Questions1. Is it possible to identify local parts of the neuronal networks that are specifically active during the different stages of seizure onset, seizure propagation and seizure termination? 2. Are seizure onset, seizure propagation and seizure termination associated with characteristic changes of the global network activity?MethodsThe electroencephalogram (EEG) is the only method that allows assessing the neuronal network activity underlying epileptic seizures at high temporal resolution in humans. We will study interdependencies of EEG signals by methods originally applied in physics to complex systems consisting of large collections of interacting elements. Specifically, to identify local parts of the neuronal networks that may be crucial during different seizure stages, dynamically formed structures will be characterized by the complementary mathematical concepts of clusters and hubs. The global network activity will be analyzed by linear as well as nonlinear methods that take into account the effects of finite time-lags due to propagation delays of neuronal activity. As a central methodological point, the results will be constantly interpreted from the viewpoint of clinical neurophysiology. The methods can thus be evaluated for their practical utility, which will influence their further development.RelevanceIf it is possible to identify, which parts of the neuronal networks and which aspects of the global network activity are associated with different seizure stages, then a rational development of new therapies might aim at specifically changing these spatial or dynamic characteristics of the epileptic brain.