Controlling seizure-like events by perturbing ion concentration dynamics with periodic stimulation.

Jeremy A Owen,John R Cressman,Ernest Barreto

doi:10.1371/journal.pone.0073820

Abstract

We investigate the effects of adding periodic stimulation to a generic, conductance-based neuron model that includes ion concentration dynamics of sodium and potassium. Under conditions of high extracellular potassium, the model exhibits repeating, spontaneous, seizure-like bursting events associated with slow modulation of the ion concentrations local to the neuron. We show that for a range of parameter values, depolarizing and hyperpolarizing periodic stimulation pulses (including frequencies lower than 4 Hz) can stop the spontaneous bursting by interacting with the ion concentration dynamics. Stimulation can also control the magnitude of evoked responses to modeled physiological inputs. We develop an understanding of the nonlinear dynamics of this system by a timescale separation procedure that identifies effective nullclines in the ion concentration parameter space. Our results suggest that the manipulation of ion concentration dynamics via external or endogenous stimulation may play an important role in neuronal excitability, seizure dynamics, and control.

Highlights

Seizure control by periodic electrical stimulation is a promising avenue for the treatment of refractory epilepsies [1,2]
We propose a basic mechanism for seizure suppression that is based on the perturbation of ion concentration dynamics by electrical stimulation
We previously studied the role of ion concentration dynamics in a similar model and identified bifurcations to stable limit cycles which correspond to very slow (*10{100 s) modulation of the ion concentrations

Summary

Introduction

Seizure control by periodic electrical stimulation is a promising avenue for the treatment of refractory epilepsies [1,2]. Experimental studies have investigated a variety of electrical stimulation protocols, observing seizure suppression both in humans [3,4,5,6] and in non-human animal or in vitro models of epilepsy [7,8]. The mechanisms that underlie this type of control are not well understood [9,10]. We propose a basic mechanism for seizure suppression that is based on the perturbation of ion concentration dynamics by electrical stimulation. Electric currents–whether they promote or suppress neuronal activity–directly impact the ion concentrations within and surrounding the affected cells, and influence the electrochemical drive of ions across the neuronal membrane

Methods

Results

Conclusion