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Alexander V. Panfilov - One of the best experts on this subject based on the ideXlab platform.
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optogenetics enables real time spatiotemporal control over Spiral Wave dynamics in an excitable cardiac system
eLife, 2018Co-Authors: Rupamanjari Majumder, Alexander V. Panfilov, Iolanda Feola, Alexander Teplenin, Antoine A F De Vries, Daniel A PijnappelsAbstract:From a spinning galaxy to a swarm of honeybees, rotating Spirals are widespread in nature. Even within the muscles of the heart, Waves of electrical activity sometimes rotate Spirally, leading to irregular heart rhythms or arrhythmia – a condition that can be fatal. Irrespective of where they occur, Spiral Waves organize around a center or core with different biophysical properties compared to the rest of the medium. The properties of the core determine the overall dynamics of the Spiral. This means that, theoretically, it should be possibly to completely control a Spiral Wave just by manipulating its core. Now, Majumder, Feola et al. have tested this long-standing hypothesis using a combination of computer modeling and experiments with single layers of rat heart cells grown in a laboratory. First, the heart cells were genetically modified so that their electrical properties could be altered with light; in other words, the cells were put under optical control. Next, by using of a narrow beam of light, Majumder, Feola et al. precisely controlled the electrical properties of a small number of cells, which then attracted and supported a rotating Spiral Wave by acting as its new core. Moving the light beam allowed the core of the Spiral Wave to be shifted too, meaning the Spiral Wave could now be steered along any desired path in the cell layer. Majumder, Feola et al. hope that these underlying principles may one day provide the basis of new treatments for irregular heartbeats that are more effective and less damaging to the heart than existing options. Yet first, more work is needed to translate these findings from single layers of cells to actual hearts.
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optogenetics enables real time spatiotemporal control over Spiral Wave dynamics in an excitable cardiac system
bioRxiv, 2018Co-Authors: Rupamanjari Majumder, Alexander V. Panfilov, Iolanda Feola, Alexander Teplenin, Antoine A F De Vries, Daniel A PijnappelsAbstract: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 afore-mentioned 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.
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Spiral Wave dynamics in a mathematical model of human ventricular tissue with myocytes and purkinje fibers
Physical Review E, 2017Co-Authors: Alok Ranjan Nayak, Alexander V. Panfilov, Rahul PanditAbstract:We present systematic numerical studies of the possible effects of the coupling of human endocardial and Purkinje cells at cellular and two-dimensional tissue levels. We find that the autorhythmic-activity frequency of the Purkinje cell in a composite decreases with an increase in the coupling strength; this can even eliminate the autorhythmicity. We observe a delay between the beginning of the action potentials of endocardial and Purkinje cells in a composite; such a delay increases as we decrease the diffusive coupling, and eventually a failure of transmission occurs. An increase in the diffusive coupling decreases the slope of the action-potential-duration-restitution curve of an endocardial cell in a composite. By using a minimal model for the Purkinje network, in which we have a two-dimensional, bilayer tissue, with a layer of Purkinje cells on top of a layer of endocardial cells, we can stabilize Spiral-Wave turbulence; however, for a sparse distribution of Purkinje-ventricular junctions, at which these two layers are coupled, we can also obtain additional focal activity and many complex transient regimes. We also present additional effects resulting from the coupling of Purkinje and endocardial layers and discuss the relation of our results to the studies performed in anatomically accurate models of the Purkinje network.
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light induced termination of Spiral Wave arrhythmias by optogenetic engineering of atrial cardiomyocytes
Cardiovascular Research, 2014Co-Authors: Brian O Bingen, Alexander V. Panfilov, Iolanda Feola, Marc C Engels, Martin J Schalij, Wanchana Jangsangthong, Zeinab Neshati, D L Ypey, Said F A Askar, Daniel A PijnappelsAbstract:Aims Atrial fibrillation (AF) is the most common cardiac arrhythmia and often involves reentrant electrical activation (e.g. Spiral Waves). Drug therapy for AF can have serious side effects including proarrhythmia, while electrical shock therapy is associated with discomfort and tissue damage. Hypothetically, forced expression and subsequent activation of light-gated cation channels in cardiomyocytes might deliver a depolarizing force sufficient for defibrillation, thereby circumventing the aforementioned drawbacks. We therefore investigated the feasibility of light-induced Spiral Wave termination through cardiac optogenetics. Methods and results Neonatal rat atrial cardiomyocyte monolayers were transduced with lentiviral vectors encoding light-activated Ca2+-translocating channelrhodopsin (CatCh; LV.CatCh∼eYFP↑) or eYFP (LV.eYFP↑) as control, and burst-paced to induce Spiral Waves rotating around functional cores. Effects of CatCh activation on reentry were investigated by optical and multi-electrode array (MEA) mapping. Western blot analyses and immunocytology confirmed transgene expression. Brief blue light pulses (10 ms/470 nm) triggered action potentials only in LV.CatCh∼eYFP↑-transduced cultures, confirming functional CatCh-mediated current. Prolonged light pulses (500 ms) resulted in reentry termination in 100% of LV.CatCh∼eYFP↑-transduced cultures ( n = 31) vs. 0% of LV.eYFP↑-transduced cultures ( n = 11). Here, CatCh activation caused uniform depolarization, thereby decreasing overall excitability (MEA peak-to-peak amplitude decreased 251.3 ± 217.1 vs. 9.2 ± 9.5 μV in controls). Consequently, functional coresize increased and phase singularities (PSs) drifted, leading to reentry termination by PS–PS or PS–boundary collisions. Conclusion This study shows that Spiral Waves in atrial cardiomyocyte monolayers can be terminated effectively by a light-induced depolarizing current, produced by the arrhythmogenic substrate itself, upon optogenetic engineering. These results provide proof-of-concept for shockless defibrillation.
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Spiral Wave dynamics in a mathematical model of human ventricular tissue with myocytes and fibroblasts
PLOS ONE, 2013Co-Authors: Alok Ranjan Nayak, Alexander V. Panfilov, T K Shajahan, Rahul PanditAbstract:Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the electrophysiological properties of cardiac tissue. We present systematic numerical studies of such modulation of electrophysiological properties in mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two-dimensional (2D) arrays of such units; our models build on earlier ones and allow for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate the dependence of the action-potential (AP) morphology on parameters such as E-f, the fibroblast resting-membrane potential, the fibroblast conductance G(f), and the MF gap-junctional coupling G(gap). Furthermore, we find that our MF composite can show autorhythmic and oscillatory behaviors in addition to an excitable response. Our 2D studies use (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various ranges for parameters such as G(gap), G(f), and E-f, and (c) intercellular couplings that can be zero-sided, one-sided, and two-sided connections of fibroblasts with myocytes. We show, in particular, that the plane-Wave conduction velocity CV decreases as a function of G(gap), for zero-sided and one-sided couplings; however, for two-sided coupling, CV decreases initially and then increases as a function of G(gap), and, eventually, we observe that conduction failure occurs for low values of G(gap). In our homogeneous studies, we find that the rotation speed and stability of a Spiral Wave can be controlled either by controlling G(gap) or E-f. Our studies with fibroblast inhomogeneities show that a Spiral Wave can get anchored to a local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude control scheme, which has been suggested for the control of Spiral-Wave turbulence in mathematical models for cardiac tissue, in our MF model both with and without heterogeneities.
Chunni Wang - One of the best experts on this subject based on the ideXlab platform.
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prediction for breakup of Spiral Wave in a regular neuronal network
Nonlinear Dynamics, 2016Co-Authors: Guodong Ren, Chunni WangAbstract:Target Wave and Spiral Wave can regulate the collective behaviors of electrical activities in neuronal systems as a powerful ‘pacemaker’. Disordered states occur when normal signal propagation among neurons is disturbed and neuronal disease could be induced. In this paper, a stable rotating Spiral Wave is developed as initial state that the two-dimensional neuronal network of Hindmarsh–Rose neuron shows distinct periodicity and regularity in space, and then, some parameters are changed sharply to model the destruction effect induced by external large forcing or internal collapse, and the destructed areas will be expanded to occupy a larger area by expanding the damaged boundary in random way. The collapse and instability of Spiral Wave, ordered states could be predicated by monitoring and analyzing the time series of some nodes. It could be useful to detect the emergence of disaster in some biological or ecological systems.
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autapse induced target Wave Spiral Wave in regular network of neurons
Science China-physics Mechanics & Astronomy, 2014Co-Authors: Huixin Qin, Chunni Wang, Runtong ChuAbstract:Autapse is a type of synapse that connects axon and dendrites of the same neuron, and the effect is often detected by close-loop feedback in axonal action potentials to the owned dendritic tree. An artificial autapse was introduced into the Hindmarsh-Rose neuron model, and a regular network was designed to detect the regular pattern formation induced by autapse. It was found that target Wave emerged in the network even when only a single autapse was considered. By increasing the (autapse density) number of neurons with autapse, for example, a regular area (2×2, 3×3, 4×4, 5×5 neurons) under autapse induced target Wave by selecting the feedback gain and time-delay in autapse. Spiral Waves were also observed under optimized feedback gain and time delay in autapses because of coherence-like resonance in the network induced by some electric autapses connected to some neurons. This confirmed that the electric autapse has a critical role in exciting and regulating the collective behaviors of neurons by generating stable regular Waves (target Waves, Spiral Waves) in the network. The Wave length of the induced travelling Wave (target Wave, Spiral Wave), because of local effect of autapse, was also calculated to understand the Waveprofile in the network of neurons.
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autapse induced Spiral Wave in network of neurons under noise
PLOS ONE, 2014Co-Authors: Huixin Qin, Chunni WangAbstract:Autapse plays an important role in regulating the electric activity of neuron by feedbacking time-delayed current on the membrane of neuron. Autapses are considered in a local area of regular network of neurons to investigate the development of spatiotemporal pattern, and emergence of Spiral Wave is observed while it fails to grow up and occupy the network completely. It is found that Spiral Wave can be induced to occupy more area in the network under optimized noise on the network with periodical or no-flux boundary condition being used. The developed Spiral Wave with self-sustained property can regulate the collective behaviors of neurons as a pacemaker. To detect the collective behaviors, a statistical factor of synchronization is calculated to investigate the emergence of ordered state in the network. The network keeps ordered state when self-sustained Spiral Wave is formed under noise and autapse in local area of network, and it independent of the selection of periodical or no-flux boundary condition. The developed stable Spiral Wave could be helpful for memory due to the distinct self-sustained property.
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Simulating the formation of Spiral Wave in the neuronal system
Nonlinear Dynamics, 2013Co-Authors: Chunni Wang, Wuyin JinAbstract:Some experimental results have confirmed that a Spiral Wave could be observed in the cortex of brain. The biological Hodgkin–Huxley neurons are used to construct a regular network with nearest-neighbor connection, artificial line defects are generated to block the traveling Wave in the network, and the potential mechanism for formation of Spiral Wave is investigated. A target Wave is generated in a local area by imposing two external forcing currents with diversity (I 0−I 1) in different areas of the network. It is confirmed that Spiral Wave could be induced by the defects even if no specific initial values are used. A single perfect Spiral Wave can occupy the network when the coupling intensity exceeds certain threshold; otherwise, a group of Spiral Waves emerges in the network. Certain channel noise can enhance the diversity (I 0−I 1) for generating target Wave, and then Spiral Waves are induced by blocking the target Wave with defects under no-flux and/or periodic boundary conditions in the network.
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chaos control Spiral Wave formation and the emergence of spatiotemporal chaos in networked chua circuits
Nonlinear Dynamics, 2012Co-Authors: Chunni Wang, Yong Liu, Long HuangAbstract:In this paper, a certain kind of intermittent scheme is used to control the chaos in a single chaotic Chua circuit to reach an arbitrary orbit. Furthermore, it is confirmed to be effective in suppressing spatiotemporal chaos and a Spiral Wave in the networks of Chua circuits with nearest-neighbor connections. The controllable and measurable variable is sampled, and the linear error between the sampled variable and the selected thresholds is fed back into the system only if the sampled variable exceeds the thresholds; otherwise, the system will develop itself without any external perturbation. In experiments, the control scheme could be realized by using the Heavside function. In the case of one single chaotic Chua circuit, the chaotic state can be controlled to reach an arbitrary n-periodical orbit (n=1,2,3,5,6,…) with appropriate feedback intensity and thresholds. It is argued that this scheme could explain the mechanism of what is called phase compression. Then the phase compression scheme is used to control a Spiral Wave and spatiotemporal chaos in a network of Chua circuits with 256×256 sites. The numerical simulation results confirm its effectiveness when appropriate upper and bottom thresholds are used by monitoring the measurable output voltages of the chaotic circuit in one site of the network.
Ryan G James - One of the best experts on this subject based on the ideXlab platform.
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hidden structures of information transport underlying Spiral Wave dynamics
Chaos, 2017Co-Authors: Hiroshi Ashikaga, Ryan G JamesAbstract:A Spiral Wave is a macroscopic dynamics of excitable media that plays an important role in several distinct systems, including the Belousov-Zhabotinsky reaction, seizures in the brain, and lethal arrhythmia in the heart. Because the Spiral Wave dynamics can exhibit a wide spectrum of behaviors, its precise quantification can be challenging. Here we present a hybrid geometric and information-theoretic approach to quantifying the Spiral Wave dynamics. We demonstrate the effectiveness of our approach by applying it to numerical simulations of a two-dimensional excitable medium with different numbers and spatial patterns of Spiral Waves. We show that, by defining the information flow over the excitable medium, hidden coherent structures emerge that effectively quantify the information transport underlying the Spiral Wave dynamics. Most importantly, we find that some coherent structures become more clearly defined over a longer observation period. These findings provide validity with our approach to quantitati...
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hidden structures of information transport underlying Spiral Wave dynamics
arXiv: Pattern Formation and Solitons, 2016Co-Authors: Hiroshi Ashikaga, Ryan G JamesAbstract:A Spiral Wave is a macroscopic dynamic of excitable media that plays an important role in several distinct systems, including the Belousov-Zhabotinsky reaction, seizures in the brain, and lethal arrhythmia in the heart. Because Spiral Wave dynamics can exhibit a wide spectrum of behaviors, its precise quantification can be challenging. Here we present a hybrid geometric and information-theoretic approach to quantifying Spiral Wave dynamics. We demonstrate the effectiveness of our approach by applying it to numerical simulations of a two-dimensional excitable medium with different numbers and spatial patterns of Spiral Waves. We show that, by defining information flow over the excitable medium, hidden coherent structures emerge that effectively quantify the information transport underlying Spiral Wave dynamics. Most importantly, we find that some coherent structures become more clearly defined over a longer observation period. These findings validate our approach to quantitatively characterize Spiral Wave dynamics by focusing on information transport. Our approach is computationally efficient and is applicable to many excitable media of interest in distinct physical, chemical and biological systems. Our approach could ultimately contribute to an improved therapy of clinical conditions such as seizures and cardiac arrhythmia by identifying potential targets of interventional therapies.
Vladimir S. Zykov - One of the best experts on this subject based on the ideXlab platform.
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Kinematics of Spiral Waves in Excitable Media
Spirals and Vortices, 2019Co-Authors: Vladimir S. ZykovAbstract:Spiral Waves rigidly rotating in excitable media sometimes play a constructive role in self-organization, while in many cases they cause an undesirable and dangerous activity. An understanding of Spiral Wave kinematics can help to control or to prevent this self-sustained activity. A description of the Spiral Wave kinematics performed by use of a free-boundary approach, reveals the selection principle which determines the shape and the rotation frequency of Spiral Waves in an unbounded medium with a given excitability. It is shown that a rigidly rotating Spiral in a medium with strongly reduced refractoriness is supported within an excitability range restricted by two universal limits. At the low excitability limit, the Spiral core radius diverges, while it vanishes at the high excitability limit and the Spiral Wave resembles the Yin-Yang pattern.
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Spiral Wave initiation in excitable media
Philosophical Transactions of the Royal Society A, 2018Co-Authors: Vladimir S. ZykovAbstract:Spiral Waves represent an important example of dissipative structures observed in many distributed systems in chemistry, biology and physics. By definition, excitable media occupy a stationary rest...
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geometrical factors in propagation block and Spiral Wave initiation
Chaos, 2017Co-Authors: Vladimir S. Zykov, Alexei Krekhov, Eberhard BodenschatzAbstract:Many theoretical and experimental studies indicate that a propagation block represents an important factor in Spiral Wave initiation in excitable media. The analytical and numerical results we obtained for a generic two-component reaction-diffusion system demonstrate quantitative conditions for the propagation block in a one-dimensional and a two-dimensional medium due to a sharp spatial increase of the medium's excitability or the coupling strength above a certain critical value. Here, we prove that this critical value strongly depends on the medium parameters and the geometry of the inhomogeneity. For an exemplary two-dimensional medium, we show how the propagation block can be used to initiate Spiral Waves by a specific choice of the size and shape of the medium's inhomogeneity.
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unusual Spiral Wave dynamics in the kessler levine model of an excitable medium
Chaos, 2015Co-Authors: Noriko Oikawa, Eberhard Bodenschatz, Vladimir S. ZykovAbstract:The Kessler-Levine model is a two-component reaction-diffusion system that describes spatiotemporal dynamics of the messenger molecules in a cell-to-cell signaling process during the aggregation of social amoeba cells. An excitation Wave arising in the model has a phase Wave at the Wave back, which simply follows the Wave front after a fixed time interval with the same propagation velocity. Generally speaking, the medium excitability and the refractoriness are two important factors which determine the Spiral Wave dynamics in any excitable media. The model allows us to separate these two factors relatively easily since the medium refractoriness can be changed independently of the medium excitability. For rigidly rotating Waves, the universal relationship has been established by using a modified free-boundary approach, which assumes that the front and the back of a propagating Wave are thin in comparison to the Wave plateau. By taking a finite thickness of the domain boundary into consideration, the validity of the proposed excitability measure has been essentially improved. A novel method of numerical simulation to suppress the Spiral Wave instabilities is introduced. The trajectories of the Spiral tip observed for a long refractory period have been investigated under a systematic variation of the medium refractoriness.
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continous transition between two limits of Spiral Wave dynamics in an excitable medium
Physical Review Letters, 2014Co-Authors: Vladimir S. Zykov, Eberhard BodenschatzAbstract:Max Planck Institute for Dynamics and Self-Organization, D-37077 Goettingen, Germany(Received 4 September 2013; revised manuscript received 10 October 2013; published 3 February 2014)By application of a free-boundary approach, we prove the existence of a continuous transition and a fullspectrum of solutions between the two known limits of Spiral Wave dynamics. We identify a controlparameterwhoseessentialimportancewas notrealized inearlierstudiesofspatiotemporal pattern selectionin excitable media. The predictions of the free-boundary approach are in good quantitative agreement withresults from numerical reaction-diffusion simulations performed on the modified Barkley model.
Hiroshi Ashikaga - One of the best experts on this subject based on the ideXlab platform.
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hidden structures of information transport underlying Spiral Wave dynamics
Chaos, 2017Co-Authors: Hiroshi Ashikaga, Ryan G JamesAbstract:A Spiral Wave is a macroscopic dynamics of excitable media that plays an important role in several distinct systems, including the Belousov-Zhabotinsky reaction, seizures in the brain, and lethal arrhythmia in the heart. Because the Spiral Wave dynamics can exhibit a wide spectrum of behaviors, its precise quantification can be challenging. Here we present a hybrid geometric and information-theoretic approach to quantifying the Spiral Wave dynamics. We demonstrate the effectiveness of our approach by applying it to numerical simulations of a two-dimensional excitable medium with different numbers and spatial patterns of Spiral Waves. We show that, by defining the information flow over the excitable medium, hidden coherent structures emerge that effectively quantify the information transport underlying the Spiral Wave dynamics. Most importantly, we find that some coherent structures become more clearly defined over a longer observation period. These findings provide validity with our approach to quantitati...
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hidden structures of information transport underlying Spiral Wave dynamics
arXiv: Pattern Formation and Solitons, 2016Co-Authors: Hiroshi Ashikaga, Ryan G JamesAbstract:A Spiral Wave is a macroscopic dynamic of excitable media that plays an important role in several distinct systems, including the Belousov-Zhabotinsky reaction, seizures in the brain, and lethal arrhythmia in the heart. Because Spiral Wave dynamics can exhibit a wide spectrum of behaviors, its precise quantification can be challenging. Here we present a hybrid geometric and information-theoretic approach to quantifying Spiral Wave dynamics. We demonstrate the effectiveness of our approach by applying it to numerical simulations of a two-dimensional excitable medium with different numbers and spatial patterns of Spiral Waves. We show that, by defining information flow over the excitable medium, hidden coherent structures emerge that effectively quantify the information transport underlying Spiral Wave dynamics. Most importantly, we find that some coherent structures become more clearly defined over a longer observation period. These findings validate our approach to quantitatively characterize Spiral Wave dynamics by focusing on information transport. Our approach is computationally efficient and is applicable to many excitable media of interest in distinct physical, chemical and biological systems. Our approach could ultimately contribute to an improved therapy of clinical conditions such as seizures and cardiac arrhythmia by identifying potential targets of interventional therapies.