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Détection et modélisation biomathématique d'évènements transitoires dans les signaux EEG intracérébraux : application au suivi de l'épileptogenèse dans un modèle murin

Abstract : Acquired epilepsies occur after a process called epileptogenesis. Although clinically silent, this process involves some functional modifications which can be observed by electroencephalography. The objectives of this thesis are i) to identify electrophysiological markers occurring during epileptogenesis, and ii) to understand which underlying pathophysiological modifications are responsible for these markers and their evolution. Firstly, using an in vivo experimental mouse model of partial epilepsy, we have monitored intracranial electrophysiological signals during epileptogenesis. We observed the emergence of pathological transient events called epileptic spikes. We have developed signal processing methods in order to automatically detect and characterize these events. Hence, we observed and quantified morphological changes of epileptic spikes during epileptogenesis. In particular, we noticed the emergence and the increase of a wave which directly follows the spike component. In this work, we defend the hypothesis that these morphological modifications can constitute markers of the epileptogenesis process in this animal model of epilepsy. Secondly, in order to interpret these electrophysiological modifications in terms of underlying pathophysiological processes, we have implemented a computational model able to simulate epileptic spikes. This neural mass model is a neurophysiologically-plausible mesoscopic representation of synaptic interactions (excitation and inhibition) in the hippocampus. Based on a sensitivity analysis of model parameters, we were able to determine some connectivity parameters that play a key role in the morphology of simulated epileptic spikes. In particular, our results show that a diminution of GABAergic inhibition leads to an increase of the aforementioned wave. Thus, using this theoretical model, we defined some hypotheses about pathophysiological modifications occurring during the epileptogenesis process. One of these hypotheses has been confirmed in blocking GABAa receptors in the in vivo mouse model, as well as in an in vitro model (rat, organotypic slices). In summary, based on the shape features of epileptic spikes, we devised an electrophysiological biomarker of epileptogenesis observed in a mouse model but useful in Human studies as well. Moreover, a computational modeling approach has permitted to suggest which pathophysiological processes might underlie this biomarker.
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Submitted on : Thursday, October 3, 2013 - 4:54:08 PM
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Clément Huneau. Détection et modélisation biomathématique d'évènements transitoires dans les signaux EEG intracérébraux : application au suivi de l'épileptogenèse dans un modèle murin. Traitement du signal et de l'image [eess.SP]. Université Rennes 1, 2013. Français. ⟨NNT : 2013REN1S043⟩. ⟨tel-00869599⟩

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