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Dynamics underlying epileptic seizures: insights from a neural mass model

par Fan, Xiaoya
Président du jury Kinnaert, Michel
Promoteur Nonclercq, Antoine
Publication Non publié, 2018-12-17

Thèse de doctorat

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Résumé :

In this work, we propose an approach that allows to explore the potential pathophysiological mechanisms (at neuronal population level) of ictogenesis by combining clinical intracranial electroencephalographic (iEEG) recordings with a neural mass model. IEEG recordings from temporal lobe epilepsy (TLE) patients around seizure onset were investigated. Physiologically meaningful parameters (average synaptic gains of the excitatory, slow and fast inhibitory population, Ae, B and G) were identified during interictal to ictal transition. We analyzed the temporal evolution of four ratios, i.e. Ae/G, Ae/B, Ae/(B + G), and B/G. The excitation/inhibition ratio increased around seizure onset and decreased before seizure offset, suggesting the disturbance and restoration of balance between excitation and inhibition around seizure onset and before seizure offset, respectively. Moreover, the slow inhibition may have an earlier effect on the breakdown of excitation/inhibition balance. Results confirm the decrease in excitation/inhibition ratio upon seizure termination in human temporal lobe epilepsy, as revealed by optogenetic approaches both in vivo in animal models and in vitro. We further explored the distribution of the average synaptic gains in parameter space and their temporal evolution, i.e. the path through the model parameter space, in TLE patients. Results showed that the synaptic gain values located roughly on a plane before seizure onset, dispersed during ictal and returned when the seizure terminated. Cluster analysis was performed on seizure paths and demonstrated consistency in synaptic gain evolution across different seizures from individual patients. Furthermore, two patient groups were identified, each one corresponding to a specific synaptic gain evolution in the parameter space during a seizure. Results were validated by a bootstrapping approach based on comparison with random paths. The differences in the path revealed variations in EEG dynamics for patients despite showing an identical seizure onset pattern. Our approach may have the potential to classify the epileptic patients into subgroups based on different mechanisms revealed by subtle changes in synaptic gains and further enable more robust decisions regarding treatment strategy. The increase of excitation/inhibition ratios, i.e. Ae/G, Ae/B and Ae/(B+G), around seizure onset makes them potential cues for seizure detection. We explored the feasibility of a model based seizure detection algorithm. A simple thresholding method was employed. We evaluated the algorithm against the manual scoring of a human expert on iEEG samples from patients suffering from different types of epilepsy. Results suggest that Ae/(B+G), i.e. excitation/(slow + fast inhibition) ratio, allowed the best performance and that the algorithm best suited TLE patients. Leave-one-out cross-validation showed that the algorithm achieved 94.74% sensitivity for TLE patients. The median false positive rate was 0.16 per hour, and median detection delay was -1.0 s. Of interest, the values of the threshold determined by leave-one-out cross-validation for TLE patients were quite constant, suggesting a general excitation/inhibition balance baseline in background iEEG among TLE patients. Such a model-based seizure detection approach is of clinical interest and could also achieve good performance for other types of epilepsy provided that more appropriate model, i.e. better describe epileptic EEG waveforms for other types of epilepsy, is implemented. Altogether, this thesis contributes to the field of epilepsy research from two perspectives. Scientifically, it gives new insights into the mechanisms underlying interictal to ictal transition, and facilitates better understanding of epileptic seizures. Clinically, it provides a tool for reviewing EEG data in a more efficient and objective manner and offers an opportunity for on-demand therapeutic devices.