Control of seizure-like dynamics in neuronal populations with excitability adaptation related to ketogenic diet.

Abstract

We consider a heterogeneous, globally coupled population of excitatory quadratic integrate-and-fire neurons with excitability adaptation due to a metabolic feedback associated with ketogenic diet, a form of therapy for epilepsy. Bifurcation analysis of a three-dimensional mean-field system derived in the framework of next-generation neural mass models allows us to explain the scenarios and suggest control strategies for the transitions between the neurophysiologically desired asynchronous states and the synchronous, seizure-like states featuring collective oscillations. We reveal two qualitatively different scenarios for the onset of synchrony. For weaker couplings, a bistability region between the lower- and the higher-activity asynchronous states unfolds from the cusp point, and the collective oscillations emerge via a supercritical Hopf bifurcation. For stronger couplings, one finds seven co-dimension two bifurcation points, including pairs of Bogdanov-Takens and generalized Hopf points, such that both lower- and higher-activity asynchronous states undergo transitions to collective oscillations, with hysteresis and jump-like behavior observed in vicinity of subcritical Hopf bifurcations. We demonstrate three control mechanisms for switching between asynchronous and synchronous states, involving parametric perturbation of the adenosine triphosphate (ATP) production rate, external stimulation currents, or pulse-like ATP shocks, and indicate a potential therapeutic advantage of hysteretic scenarios.