Neural mass modeling of slow-fast dynamics of seizure initiation and abortion.

Elif Köksal Ersöz,Fabrice Bartolomei,Fabrice Wendling,Julien Modolo,Peter Neal Taylor

doi:10.1371/journal.pcbi.1008430

Elif Köksal Ersöz, Fabrice Bartolomei + Show 3 more

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https://doi.org/10.1371/journal.pcbi.1008430

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Abstract

Epilepsy is a dynamic and complex neurological disease affecting about 1% of the worldwide population, among which 30% of the patients are drug-resistant. Epilepsy is characterized by recurrent episodes of paroxysmal neural discharges (the so-called seizures), which manifest themselves through a large-amplitude rhythmic activity observed in depth-EEG recordings, in particular in local field potentials (LFPs). The signature characterizing the transition to seizures involves complex oscillatory patterns, which could serve as a marker to prevent seizure initiation by triggering appropriate therapeutic neurostimulation methods. To investigate such protocols, neurophysiological lumped-parameter models at the mesoscopic scale, namely neural mass models, are powerful tools that not only mimic the LFP signals but also give insights on the neural mechanisms related to different stages of seizures. Here, we analyze the multiple time-scale dynamics of a neural mass model and explain the underlying structure of the complex oscillations observed before seizure initiation. We investigate population-specific effects of the stimulation and the dependence of stimulation parameters on synaptic timescales. In particular, we show that intermediate stimulation frequencies (>20 Hz) can abort seizures if the timescale difference is pronounced. Those results have the potential in the design of therapeutic brain stimulation protocols based on the neurophysiological properties of tissue.

Highlights

IntroductionMulti-causal chronic disease defined by the recurrence of unpredictable seizures that severely affect patients’ quality of life
Epilepsy is a severe, multi-causal chronic disease defined by the recurrence of unpredictable seizures that severely affect patients’ quality of life
Epilepsy is a complex disease affecting 1% of the worldwide population of which 30% of the patients are drug-resistant and seeking for alternative therapeutic methods, such as neurostimulation

Summary

Introduction

Multi-causal chronic disease defined by the recurrence of unpredictable seizures that severely affect patients’ quality of life. In 30% of patients, antiepileptic drugs [1] remain inefficient to control the occurrence of seizures. Drug-resistant epilepsies are ‘focal’ [2], as characterized by an epileptogenic zone (EZ) that is relatively circumscribed in one of the two cerebral hemispheres. Surgical treatment can only be offered to 15– 20% drug-resistant patients [6] in whom the benefit-to-deficit ratio is favorable. Doedel EJ, Champneys A, Fairgrieve TF, Yu AB, Kuznetsov AP, Oldeman BE, et al Auto-07p: Continuation and bifurcation software for ordinary differential equations.

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