Unconventional Collective Resonance as Nonlinear Mechanism of Ectopic Activity in Excitable Media

TL;DR

This paper uncovers a novel nonlinear resonance mechanism in excitable media that does not rely on intrinsic oscillations, involving coupling between excitable and monostable regions, with implications for biological systems like cardiac tissue.

Contribution

It introduces a new collective resonance mechanism based on wave interactions in coupled excitable and monostable media, supported by models and experiments.

Findings

Resonance arises from wave coupling, not intrinsic oscillations.

High-frequency waves can suppress ectopic activity.

The mechanism is demonstrated in models, experiments, and simulations.

Abstract

Many physical, chemical and biological processes rely on intrinsic oscillations to employ resonance responses to external stimuli of certain frequency. Such resonance phenomena in biological systems are typically explained by one of two mechanisms: either a classical linear resonance of harmonic oscillator, or entrainment and phase locking of nonlinear limit cycle oscillators subjected to periodic forcing. Here, we discover a nonlinear mechanism, which does not require intrinsic oscillations. Instead, the resonant frequency dependence arises from coupling between an excitable and a monostable region of the medium. This composite system is endowed with emergent bistability between a stable steady state and stable spatiotemporal oscillations. The resonant transition from stable state to oscillatory state is induced by waves of particular frequency travelling through the medium. This transition to the spatiotemporal oscillatory state requires accumulation of multiple waves, resulting in the exclusion of lower frequencies. The cutting off of high frequencies is realized by damping of wave amplitude in the monostable zone and then by activating amplitude sensitive dynamics in the monostable units. We demonstrate this new resonance mechanism in a simplistic reaction-diffusion model. Also, we reveal this collective resonance mechanism in in-vitro experiments and detailed biophysical simulations representing a major type of arrhythmia. We further demonstrate, both experimentally and theoretically, that the ongoing spatiotemporal oscillations, such as ectopic activity in cardiac tissue, can be stopped by travelling waves of high frequency. Overall, we claim the universality of this resonance mechanism in a broad class of nonlinear biophysical systems. Specifically, we hypothesize that such phenomena could be found in neuronal systems as an alternative to traditional resonant processes.