Optogenetics enables real-time spatiotemporal control over spiral wave dynamics in an excitable cardiac system

Propagation of non-linear waves is key to the functioning of diverse biological systems. Such waves can organize into spirals, rotating around a core, whose properties determine the overall wave dynamics. Theoretically, manipulation of a spiral wave core should lead to full spatiotemporal control over its dynamics. However, this theory lacks supportive evidence (even at a conceptual level), making it thus a long-standing hypothesis. Here, we propose a new phenomenological concept that involves artificially dragging spiral waves by their cores, to prove the aforementioned hypothesis in silico, with subsequent in vitro validation in optogenetically modified monolayers of rat atrial cardiomyocytes. We thereby connect previously established, but unrelated concepts of spiral wave attraction, anchoring and unpinning to demonstrate that core manipulation, through controlled displacement of heterogeneities in excitable media, allows forced movement of spiral waves along pre-defined trajectories. Consequently, we impose real-time spatiotemporal control over spiral wave dynamics in a biological system

Negative tension of scroll wave filaments and turbulence in three-dimensional excitable media and application in cardiac dynamics

Scroll waves are vortices that occur in three-dimensional excitable media. Scroll waves have been observed in a variety of systems including cardiac tissue, where they are associated with cardiac arrhythmias. The disorganization of scroll waves into chaotic behavior is thought to be the mechanism of ventricular fibrillation, whose lethality is widely known. One possible mechanism for this process of scroll wave instability is negative filament tension. It was discovered in 1987 in a simple two variables model of an excitable medium. Since that time, negative filament tension of scroll waves and the resulting complex, often turbulent dynamics was studied in many generic models of excitable media as well as in physiologically realistic models of cardiac tissue. In this article, we review the work in this area from the first simulations in FitzHugh-Nagumo type models to recent studies involving detailed ionic models of cardiac tissue. We discuss the relation of negative filament tension and tissue excitability and the effects of discreteness in the tissue on the filament tension. Finally, we consider the application of the negative tension mechanism to computational cardiology, where it may be regarded as a fundamental mechanism that explains differences in the onset of arrhythmias in thin and thick tissue

Nonlinear physics of electrical wave propagation in the heart: a review

The beating of the heart is a synchronized contraction of muscle cells (myocytes) that are triggered by a periodic sequence of electrical waves (action potentials) originating in the sino-atrial node and propagating over the atria and the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF) or ventricular tachycardia (VT) are caused by disruptions and instabilities of these electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent wave patterns (AF,VF). Numerous simulation and experimental studies during the last 20 years have addressed these topics. In this review we focus on the nonlinear dynamics of wave propagation in the heart with an emphasis on the theory of pulses, spirals and scroll waves and their instabilities in excitable media and their application to cardiac modeling. After an introduction into electrophysiological models for action potential propagation, the modeling and analysis of spatiotemporal alternans, spiral and scroll meandering, spiral breakup and scroll wave instabilities like negative line tension and sproing are reviewed in depth and discussed with emphasis on their impact in cardiac arrhythmias.Peer ReviewedPreprin

Topological constraints on spiral wave dynamics in spherical geometries with inhomogeneous excitability

We analyze the way topological constraints and inhomogeneity in the excitability influence the dynamics of spiral waves on spheres and punctured spheres of excitable media. We generalize the definition of an index such that it characterizes not only each spiral but also each hole in punctured, oriented, compact, two-dimensional differentiable manifolds and show that the sum of the indices is conserved and zero. We also show that heterogeneity and geometry are responsible for the formation of various spiral wave attractors, in particular, pairs of spirals in which one spiral acts as a source and a second as a sink -- the latter similar to an antispiral. The results provide a basis for the analysis of the propagation of waves in heterogeneous excitable media in physical and biological systems.Comment: 5 pages, 6 Figures, major revisions, accepted for publication in Phys. Rev.

Localization of response functions of spiral waves in the FitzHugh-Nagumo system

Dynamics of spiral waves in perturbed, e. g. slightly inhomogeneous or subject to a small periodic external force, two-dimensional autowave media can be described asymptotically in terms of Aristotelean dynamics, so that the velocities of the spiral wave drift in space and time are proportional to the forces caused by the perturbation. The forces are defined as a convolution of the perturbation with the spiral's Response Functions, which are eigenfunctions of the adjoint linearised problem. In this paper we find numerically the Response Functions of a spiral wave solution in the classic excitable FitzHugh-Nagumo model, and show that they are effectively localised in the vicinity of the spiral core.Comment: 11 pages, 2 figure

Attraction of Spiral Waves by Localized Inhomogeneities with Small-World Connections in Excitable Media

Trapping and un-trapping of spiral tips in a two-dimensional homogeneous excitable medium with local small-world connections is studied by numerical simulation. In a homogeneous medium which can be simulated with a lattice of regular neighborhood connections, the spiral wave is in the meandering regime. When changing the topology of a small region from regular connections to small-world connections, the tip of a spiral waves is attracted by the small-world region, where the average path length declines with the introduction of long distant connections. The "trapped" phenomenon also occurs in regular lattices where the diffusion coefficient of the small region is increased. The above results can be explained by the eikonal equation and the relation between core radius and diffusion coefficient.Comment: 5 pages, 4 figure

Response to sub-threshold stimulus is enhanced by spatially heterogeneous activity

Sub-threshold stimuli cannot initiate excitations in active media, but surprisingly as we show in this paper, they can alter the time-evolution of spatially heterogeneous activity by modifying the recovery dynamics. This results in significant reduction of waveback velocity which may lead to spatial coherence, terminating all activity in the medium including spatiotemporal chaos. We analytically derive model-independent conditions for which such behavior can be observed.Comment: 5 pages, 5 figure