Long term evolution of fast ripples during epileptogenesis.

Fast ripples (FRs) have received considerable attention in the last decade since they represent an electrophysiological biomarker of the epileptogenic zone (EZ). However, the real dynamics underlying the occurrence, amplitude, and time-frequency content of FRs generation during epileptogenesis are still not well understood. This work aims at characterizing and explaining the evolution of these features.Intracortical electroencephalographic signals recorded in a kainate mouse model of temporal lobe epilepsy were processed in order to compute specific FR features. Then realistic physiologically based computational modeling was employed to explore the different elements that can explain the mechanisms of epileptogenesis and simulate the recorded FR in the early and late latent period.Results indicated that continuous changes of FR features are mainly portrayed by the epileptic (pathological) tissue size and synaptic properties. Furthermore, the microelectrodes characteristics were found to dramatically affect the observability and spectral/temporal content of FRs. Consequently, FRs evolution seems to mirror the continuous pathophysiological mechanism changes that occur during epileptogenesis as long as the microelectrode properties are taken into account.Our study suggests that FRs can account for the pathophysiological changes which might explain the EZ generation and evolution and can contribute in the treatment plan of pharmaco-resistant epilepsies.