Delayed global feedback in the genesis and stability of spatiotemporal excitation patterns in paced biological excitable media

Zhen Song and Zhilin Qu

PLOS Computational Biology, 2020, vol. 16, issue 10, 1-23

Abstract: Biological excitable media, such as cardiac or neural cells and tissue, exhibit memory in which a change in the present excitation may affect the behaviors in the next excitation. For example, a change in calcium (Ca2+) concentration in a cell in the present excitation may affect the Ca2+ dynamics in the next excitation via bi-directional coupling between voltage and Ca2+, forming a delayed feedback loop. Since the Ca2+ dynamics inside the excitable cells are spatiotemporal while the membrane voltage is a global signal, the feedback loop is then a delayed global feedback (DGF) loop. In this study, we investigate the roles of DGF in the genesis and stability of spatiotemporal excitation patterns in periodically-paced excitable media using mathematical models with different levels of complexity: a model composed of coupled FitzHugh-Nagumo units, a 3-dimensional physiologically-detailed ventricular myocyte model, and a coupled map lattice model. We investigate the dynamics of excitation patterns that are temporal period-2 (P2) and spatially concordant or discordant, such as subcellular concordant or discordant Ca2+alternans in cardiac myocytes or spatially concordant or discordant Ca2+ and repolarization alternans in cardiac tissue. Our modeling approach allows both computer simulations and rigorous analytical treatments, which lead to the following results and conclusions. When DGF is absent, concordant and discordant P2 patterns occur depending on initial conditions with the discordant P2 patterns being spatially random. When the DGF is negative, only concordant P2 patterns exist. When the DGF is positive, both concordant and discordant P2 patterns can occur. The discordant P2 patterns are still spatially random, but they satisfy that the global signal exhibits a temporal period-1 behavior. The theoretical analyses of the coupled map lattice model reveal the underlying instabilities and bifurcations caused by the DGF for the genesis, selection, and stability of spatiotemporal excitation patterns.Author summary: Understanding the mechanisms of pattern formation in biological systems is of great importance. Here we investigate the dynamical mechanisms by which delayed global feedback affects excitation pattern formation and stability in periodically-paced biological excitable media, such as cardiac or neural cells and tissue. We focus on the formation and stability of the temporal period-2 and spatially in-phase and out-of-phase excitation patterns. Using models of different levels of complexity, we show that when the delayed global feedback is negative, only the spatially in-phase patterns are stable. When the feedback is positive, both spatially in-phase and out-of-phase patterns are stable, and the out-of-phase patterns are spatially random but satisfy that the global signals are temporal period-1 solutions.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1007931

DOI: 10.1371/journal.pcbi.1007931

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