Computational modeling of epileptiform activities in medial temporal lobe epilepsy combined with in vitro experiments

Abstract

In this paper, we propose a comprehensive computational model that is able to reproduce three epileptiform activities. The model targets a hippocampal formation that is known to be an important lesion in medial temporal lobe epilepsy. It consists of four sub-networks consisting of excitatory and inhibitory neurons and well-known signal pathways, with consideration of propagation delay. The three epileptiform activities involve fast and slow interictal discharge and ictal discharge, and those activities can be induced in vitro by application of 4-Aminopyridine in entorhinal cortex combined hippocampal slices. We model the three epileptiform activities upon previously reported biological mechanisms and verify the simulation results by comparing them with in vitro experimental data obtained using a microelectrode array. We use the results of Granger causality analysis of recorded data to set input gains of signal pathways in the model, so that the compatibility between the computational and experimental models can be improved. The proposed model can be expanded to evaluate the suppression effect of epileptiform activities due to new treatment methods.