Chaotic and stochastic dynamics of epileptiform-like activities in sclerotic hippocampus resected from patients with pharmacoresistant epilepsy

摘要

Author summaryTemporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults and hippocampal sclerosis is the major pathophysiological substrate of pharmaco-refractory TLE. Different patterns of epileptiform-like activity have been described in human hippocampal sclerosis, but the standard analysis applied to characterize the activities usually do not consider the nonlinear features that epileptiform patterns exhibit. Here, using Poincare map and Recurrence Quantitative Analysis we characterized the most prevalent type of epileptiform-like activities-interictal-like events (II) and periodic ictal spiking (PIS), recorded in vitro from resected hippocampi of pharmacoresistant patients with TLE-according to their levels of stochasticity, chaoticity and determinism. The II activities showed to be more chaotic with complex rhythmicity than PIS activities. The nonlinear dynamic differences between II and PIS leads us to conjecture that they are expressions of different seizure susceptibility. We also identified that each hippocampal subfield expresses II and PIS activities in a specific and different way. Finally, from the modulation of internal parameters of two computational models, we show the conversion of one type of activity into the other, showing how specific neuron networks synchronize over time, leading to II and PIS activities and then into a generalized seizure. The types of epileptiform activity occurring in the sclerotic hippocampus with highest incidence are interictal-like events (II) and periodic ictal spiking (PIS). These activities are classified according to their event rates, but it is still unclear if these rate differences are consequences of underlying physiological mechanisms. Identifying new and more specific information related to these two activities may bring insights to a better understanding about the epileptogenic process and new diagnosis. We applied Poincare map analysis and Recurrence Quantification Analysis (RQA) onto 35 in vitro electrophysiological signals recorded from slices of 12 hippocampal tissues surgically resected from patients with pharmacoresistant temporal lobe epilepsy. These analyzes showed that the II activity is related to chaotic dynamics, whereas the PIS activity is related to deterministic periodic dynamics. Additionally, it indicates that their different rates are consequence of different endogenous dynamics. Finally, by using two computational models we were able to simulate the transition between II and PIS activities. The RQA was applied to different periods of these simulations to compare the recurrences between artificial and real signals, showing that different ranges of regularity-chaoticity can be directly associated with the generation of PIS and II activities.