Falling off a limit cycle using phase-agnostic stimuli: Applications to clinical oscillopathies

Abstract

For over a century, physiological studies have shown that precisely timed pulses can switch off a biological oscillator. This empiric finding has shaped our mechanistic understanding of how perturbations start, stop, and reset biological oscillators and has led to treatments that suppress pathological oscillations using electrical pulses given within specified therapeutic phase windows. Here, we present evidence, using numerical simulations of models of epileptic seizures and reentrant tachycardia, that the phase window can be opened to the entire cycle using novel complex stimulus waveforms. Our results reveal that the trajectories are displaced by such phase-agnostic stimuli off the oscillator's limit cycle and corralled into a region where oscillation is suppressed, irrespective of the phase at which the stimulus was applied. Our findings suggest the need for broadening theoretical understanding of how complex perturbing waveforms interact with biological oscillators to access their arrhythmic states. In clinical practice, oscillopathies may be treated more effectively with non-traditional stimulus waveforms that obviate the need for phase specificity.