Assessing the neuronal network activity underlying human epileptic seizures

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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.