Singular Hopf bifurcations and mixed-mode oscillations in a two-cell inhibitory neural network

Recent studies of a firing rate model for neural competition as observed in binocular rivalry and central pattern generators [R. Curtu, A. Shpiro, N. Rubin, J. Rinzel, Mechanisms for frequency control in neuronal competition models, SIAM J. Appl. Dyn. Syst. 7 (2) (2008) 609-649] showed that the variation of the stimulus strength parameter can lead to rich and interesting dynamics. Several types of behavior were identified such as: fusion, equivalent to a steady state of identical activity levels for both neural units; oscillations due to either an escape or a release mechanism; and a winner-take-all state of bistability. The model consists of two neural populations interacting through reciprocal inhibition, each endowed with a slow negative-feedback process in the form of spike frequency adaptation. In this paper we report the occurrence of another complex oscillatory pattern, the mixed-mode oscillations (MMOs). They exist in the model at the transition between the relaxation oscillator dynamical regime and the winner-take-all regime. The system distinguishes itself from other neuronal models where MMOs were found by the following interesting feature: there is no autocatalysis involved (as in the examples of voltage-gated persistent inward currents and/or intrapopulation recurrent excitation) and therefore the two cells in the network are not intrinsic oscillators; the oscillations are instead a combined result of the mutual inhibition and the adaptation. We prove that the MMOs are due to a singular Hopf bifurcation point situated in close distance to the transition point to the winner-take-all case. We also show that in the vicinity of the singular Hopf other types of bifurcations exist and we construct numerically the corresponding diagrams.     

Introduction to focus issue: mixed mode oscillations: experiment, computation, and analysis

Mixed mode oscillations (MMOs) occur when a dynamical system switches between fast and slow motion and small and large amplitude. MMOs appear in a variety of systems in nature, and may be simple or complex. This focus issue presents a series of articles on theoretical, numerical, and experimental aspects of MMOs. The applications cover physical, chemical, and biological systems.     

Mixed-mode oscillations in a stochastic,piecewise-linear system

We analyse a piecewise-linear FitzHugh–Nagumo model. The system exhibits a canard near which both small amplitude and large amplitude periodic orbits exist. The addition of small noise induces mixed-mode oscillations (MMOs) in the vicinity of the canard point. We determine the effect of each model parameter on the stochastically driven MMOs. In particular we show that any parameter variation (such as a modification of the piecewise-linear function in the model) that leaves the ratio of noise amplitude to time-scale separation unchanged typically has little effect on the width of the interval of the primary bifurcation parameter over which MMOs occur. In that sense, the MMOs are robust. Furthermore, we show that the piecewise-linear model exhibits MMOs more readily than the classical FitzHugh–Nagumo model for which a cubic polynomial is the only nonlinearity. By studying a piecewise-linear model, we are able to explain results using analytical expressions and compare these with numerical investigations.     

From simple to complex oscillatory behavior in metabolic and genetic control networks

We present an overview of mechanisms responsible for simple or complex oscillatory behavior in metabolic and genetic control networks. Besides simple periodic behavior corresponding to the evolution toward a limit cycle we consider complex modes of oscillatory behavior such as complex periodic oscillations of the bursting type and chaos. Multiple attractors are also discussed, e.g., the coexistence between a stable steady state and a stable limit cycle (hard excitation), or the coexistence between two simultaneously stable limit cycles (birhythmicity). We discuss mechanisms responsible for the transition from simple to complex oscillatory behavior by means of a number of models serving as selected examples. The models were originally proposed to account for simple periodic oscillations observed experimentally at the cellular level in a variety of biological systems. In a second stage, these models were modified to allow for complex oscillatory phenomena such as bursting, birhythmicity, or chaos. We consider successively (1) models based on enzyme regulation, proposed for glycolytic oscillations and for the control of successive phases of the cell cycle, respectively; (2) a model for intracellular Ca(2+) oscillations based on transport regulation; (3) a model for oscillations of cyclic AMP based on receptor desensitization in Dictyostelium cells; and (4) a model based on genetic regulation for circadian rhythms in Drosophila. Two main classes of mechanism leading from simple to complex oscillatory behavior are identified, namely (i) the interplay between two endogenous oscillatory mechanisms, which can take multiple forms, overt or more subtle, depending on whether the two oscillators each involve their own regulatory feedback loop or share a common feedback loop while differing by some related process, and (ii) self-modulation of the oscillator through feedback from the system's output on one of the parameters controlling oscillatory behavior. However, the latter mechanism may also be viewed as involving the interplay between two feedback processes, each of which might be capable of producing oscillations. Although our discussion primarily focuses on the case of autonomous oscillatory behavior, we also consider the case of nonautonomous complex oscillations in a model for circadian oscillations subjected to periodic forcing by a light-dark cycle and show that the occurrence of entrainment versus chaos in these conditions markedly depends on the wave form of periodic forcing. (c) 2001 American Institute of Physics.     

On decomposing mixed-mode oscillations and their return maps

Alternating patterns of small and large amplitude oscillations occur in a wide variety of physical, chemical, biological, and engineering systems. These mixed-mode oscillations (MMOs) are often found in systems with multiple time scales. Previous differential equation modeling and analysis of MMOs have mainly focused on local mechanisms to explain the small oscillations. Numerical continuation studies reported different MMO patterns based on parameter variation. This paper aims at improving the link between local analysis and numerical simulation. Our starting point is a numerical study of a singular return map for the Koper model which is a prototypical example for MMOs, which also relates to local normal form theory. We demonstrate that many MMO patterns can be understood geometrically by approximating the singular maps with affine and quadratic maps. Motivated by our numerical analysis we use abstract affine and quadratic return map models in combination with two local normal forms that generate small oscillations. Using this decomposition approach we can reproduce many classical MMO patterns and effectively decouple bifurcation parameters for local and global parts of the flow. The overall strategy we employ provides an alternative technique for understanding MMOs.     

The Ginzburg-Landau approach to oscillatory media

Close to a supercritical Hopf bifurcation, oscillatory media may be described, by the complex Ginzburg-Landau equation. The most important spatiotemporal behaviors associated with this dynamics are reviewed here. It is shown, on a few concrete examples, how real chemical oscillators may be described by this equation, and how its coefficients may be obtained from the experimental data. Furthermore, the effect of natural forcings, induced by the experimental realization of chemical oscillators in batch reactors, may also be studied in the framework of complex Ginzburg-Landau equations and its associated phase dynamics. We show, in particular, how such forcings may locally transform oscillatory media into excitable ones and trigger the formation of complex spatiotemporal patterns.     

Mixed-mode oscillations and chaos from a simple second-order oscillator under weak periodic perturbation

In this study, we propose a remarkably simple oscillator that exhibits extremely complicated behaviors. The second-order nonautonomous differential equation discussed in this Letter is considered to be one of the simplest dynamics that can produce mixed-mode oscillations (MMOs) and chaos. Our model uses a Bonhoeffer-van der Pol (BVP) oscillator under weak periodic perturbation. The parameter set of the BVP equation is chosen such that a focus and a relaxation oscillation coexist when no perturbation is applied. Under weak periodic perturbation, various types of MMOs and chaos with remarkably complicated waveforms are observed.     

Bifurcations of mixed-mode oscillations in a stellate cell model

Experimental recordings of the membrane potential of stellate cells within the entorhinal cortex show a transition from subthreshold oscillations (STOs) via mixed-mode oscillations (MMOs) to relaxation oscillations under increased injection of depolarizing current. Acker et al. introduced a 7D conductance based model which reproduces many features of the oscillatory patterns observed in these experiments. For the first time, we present a comprehensive bifurcation analysis of this model by using the software package AUTO. In particular, we calculate the stable MMO branches within the bifurcation diagram of this model, as well as other MMO patterns which are unstable. We then use geometric singular perturbation theory to demonstrate how the bifurcations are governed by a 3D reduced model introduced by Rotstein et al. We extend their analysis to explain all observed MMO patterns within the bifurcation diagram. A key role in this bifurcation analysis is played by a novel homoclinic bifurcation structure connecting to a saddle equilibrium on the unstable branch of the corresponding critical manifold. This type of homoclinic connection is possible due to canards of folded node (folded saddle-node) type.     

Discrete-time stimulation of the oscillatory and excitable forms of a FitzHugh-Nagumo model applied to the pulsatile release of luteinizing hormone releasing hormone

A model for the pulsatile release of luteinizing hormone releasing hormone (LHRH) can be reduced to a FitzHugh-Nagumo model subject to regular and quasiregular (i.e., with slight random variation in the interstimulus interval), discrete-time stimulation. The relationship of output pulse frequency (OPF) to stimulus frequency is compared between the excitable and oscillatory forms of the model and discussed in the context of results from other pulse-driven model systems. Some examples of the changes in OPF caused by quasiregular and purely Poissonian stimuli are given for the excitable case. The unstimulated system frequently interacts with the stimulation in such a complex manner that the OPF bears little resemblance to the frequency of stimulation or of the unstimulated system. Furthermore, the inability of the oscillatory form of the model to allow complete suppression of output pulses for moderate stimulation frequencies suggests that the LHRH system can be more appropriately described by the excitable form of the model. (c) 1995 American Institute of Physics.     

The selection of mixed-mode oscillations in a Hodgkin-Huxley model with multiple timescales

In recent work [J. Rubin and M. Wechselberger, Biol. Cybern. 97, 5 (2007)], we explained the appearance of remarkably slow oscillations in the classical Hodgkin-Huxley (HH) equations, modified by scaling a time constant, using recently developed theory about mixed-mode oscillations (MMOs). This theory is only rigorously valid, however, for epsilon sufficiently small, where epsilon is a parameter that arises from nondimensionalization of the HH system. Here, we illustrate how the parameter regime over which MMOs exist, and the features of the MMO patterns within this regime, vary with respect to several key parameters in the nondimensionalized HH equations, including epsilon. Moreover, we explain our findings in terms of the effects that these parameters are expected to have on certain organizing structures within the corresponding flow, generalized from analysis done previously in the singular limit.     

Mixed-mode oscillations and cluster patterns in an electrochemical relaxation oscillator under galvanostatic control

We studied the dynamics of a prototypical electrochemical model, the electro-oxidation of hydrogen in the presence of poisons, under galvanostatic conditions. The lumped system exhibits relaxation oscillations, which develop mixed-mode oscillations (MMOs) for low preset currents. A fast-slow analysis of the homogeneous dynamics reveals that the MMOs arise from a fast oscillating subsystem and a one-dimensional slow manifold. In the spatially extended system, the galvanostatic constraint imposes a synchronizing global coupling that drives the system into cluster patterns. The properties of the cluster patterns (CPs) result from an intricate interplay of the nature of the local oscillators, the global constraint, and a nonlocal coupling through the electrolyte. In particular, we find that the global constraint suppresses small-amplitude oscillations of MMOs and prevents domains oscillating out of phase from occupying equal regions in phase space. The nonlocal coupling causes each individual clustered region to oscillate on a different limit cycle. Typically multistability of CPs is found. Coexisting patterns possess different oscillation periods and a different total fraction in space that occupies the in-phase or out-of-phase state, respectively.     

Oscillatory Flow Phenomena in Simple and Complex Fluids

Pulsatile and oscillatory flows are prevalent in many biological, industrial, and natural systems. Nuclear magnetic resonance (NMR) is a noninvasive method for evaluating fluid mechanics and can be used to obtain spatially resolved velocity maps in simple and complex fluids. A system has been constructed to provide a controllable and predictable oscillatory flow in order to gain a better understanding of the impact of oscillatory flow on Newtonian and non-Newtonian fluids, specifically water, xanthan gum, polyacrylamide and a colloidal suspension. A core shell particle colloidal suspension is used as a model system since measurements can be obtained separately from the suspending fluid (water) and the liquid particle core (hexadecane oil) using NMR. The oscillatory flow system coupled with NMR measures the velocity distributions and dynamics of the fluid undergoing oscillatory flow at specific points in the oscillation cycle.     

Self-sustained oscillations of complex genomic regulatory networks

Recently, self-sustained oscillations in complex networks consisting of non-oscillatory nodes have attracted great interest in diverse natural and social fields. Oscillatory genomic regulatory networks are one of the most typical examples of this kind. Given an oscillatory genomic network, it is important to reveal the central structure generating the oscillation. However, if the network consists of large numbers of genes and interactions, the oscillation generator is deeply hidden in the complicated interactions. We apply the dominant phase-advanced driving path method proposed in Qian et al. (2010) [1] to reduce complex genomic regulatory networks to one-dimensional and unidirectionally linked network graphs where negative regulatory loops are explored to play as the central generators of the oscillations, and oscillation propagation pathways in the complex networks are clearly shown by tree branches radiating from the loops. Based on the above understanding we can control oscillations of genomic networks with high efficiency.     

MR imaging of oscillatory magnetic field changes: Progressing from phantom to human

Detection of ultra-weak oscillatory magnetic field changes using MRI is of great research interest not only for neuronal current MRI of endogenous neuronal oscillations but also for direct visualization of exogenous transcranial currents or iron oxide contrast agent distribution. In this work, we present a novel oscillatory-selective detection (OSD) method that is magnitude-sensitive to the oscillatory magnetic field changes and immune to the main field inhomogeneity. In OSD, a train of 180° pulses with alternating polarity and mirror symmetry are used to refocus and accumulate magnetization changes induced by external oscillatory fields. After taking both the signal change and image signal-to-noise ratio (SNR) into account, a final 90° pulse with a phase offset of 45° is applied to store a combination of the current-induced signal change and background magnetization for the subsequent EPI acquisition. Its performance was demonstrated in phantom and human studies, both of which showed much better detection in the comparison with the recently proposed spin-lock oscillatory excitation (SLOE) method. OSD was further successfully applied in imaging transcranial alternating current stimulation (tACS) induced field changes in the human brain. These promising results suggest that OSD can overcome the limitation of field inhomogeneity impeding previous oscillatory current MRI sensitivity and be a viable tool in future tACS study.     

Network dynamics and its relationships to topology and coupling structure in excitable complex networks

All dynamic complex networks have two important aspects, pattern dynamics and network topology. Discovering different types of pattern dynamics and exploring how these dynamics depend or/network topologies are tasks of both great theoretical importance and broad practical significance. In this paper we study the oscillatory behaviors of excitable complex networks （ECNs） and find some interesting dynamic behaviors of ECNs in oscillatory probability, the multiplicity of oscillatory attractors, period distribution, and different types of oscillatory patterns （e.g., periodic, quasiperiodic, and chaotic）. In these aspects, we further explore strikingly sharp differences among network dynamics induced by different topologies （random or scale-free topologies） and different interaction structures （symmetric or asymmetric couplings）. The mechanisms behind these differences are explained physically.     

Bifurcations in autonomous mechanical systems under the influence of joint damping

This contribution deals with the impact of joint damping on two classes of stability problems which are often found in engineering problems. In a first part, the principle structure of the equations of motion is derived when joints are modeled using Masing-, Prandtl- and Coulomb-elements. For these general formulations, some fundamental statements concerning stability and attractiveness of steady-state solutions may be given for large amplitudes and configurations which are not too close to the linear stability threshold. The second part focuses on analyzing the behavior at small amplitudes and in the vicinity of the linear stability threshold in more detail: to this end, a static stability problem (buckling) and two oscillatory self-excitation mechanisms (negative damping, non-conservative coupling) are discussed. For all considered problems, adding joint damping transforms the equilibrium points into sets of equilibria and bifurcations of the non-smooth problems occur near the linear stability threshold. Concerning the buckling problem adding joint damping does not alter the behavior fundamentally: still a local bifurcation occurs and attractiveness or instability of equilibrium solutions is preserved. In contrast, the oscillatory instability examples are strongly influenced by joint damping: here, global discontinuous bifurcations may occur. Besides the joint friction also the joint-stiffness may play a crucial role, since it determines whether attractive solutions in or about the equilibrium set exist. It is found that only in some cases a linear stability analysis of the corresponding system without joints may give correct indications on the behavior: consequently, neglecting joint-damping in stability analyses may lead to wrong results concerning self-excitation.     

Regge oscillations in integral cross sections for proton impact on atomic hydrogen

The integral cross sections for elastic scattering and spin exchange for proton impact on atomic hydrogen show several oscillations in the energy range 0.01-1.0 eV that cannot be associated with resonances or the glory effect. A complex angular momentum analysis using computed Regge trajectories shows that each peak of the oscillatory structure is predominantly associated with at most three trajectories. In this way, the peaks are related to the L=0 bound states of H+ 2. The complex angular momentum theory for integral cross sections that we introduce shows that such oscillations are a general feature of potential scattering.     

The application of chemical reduction methods to a combustion system exhibiting complex dynamics

A number of chemical model reduction techniques have been developed over recent years with a growing range of applications in combustion. The following work demonstrates the application of such reduction techniques for a combustion system describing the oxidation of carbon monoxide + hydrogen in a continuously stirred tank reactor (CSTR) at very low pressure. The system exhibits complex dynamics including oscillatory glow, oscillatory ignition and mixed mode oscillations. It is demonstrated that a range of local reduction methods can be applied to such complex systems, as long as sufficient coverage of the accessed regions of phase space are included in the reduction analysis. The methods include sensitivity analysis, the quasi-steady state approximation (QSSA) and repro-modelling based on the concept of an intrinsic low dimensional manifold (ILDM). The system is qualitatively different from some previous applications of ILDM methods where trajectories tend towards a fixed equilibrium. The underlying dimension of the system is seen to vary throughout selected trajectories with rapid increases occurring over very short time-scales during oscillatory ignition. Nevertheless, a final reduced model of only four variables is developed using fitted orthonormal polynomials describing the system dynamics on a slow manifold. The application serves to demonstrate that the relationship between local reduced model error and global errors can be complex for systems exhibiting complex dynamics, with regions of seemingly small local mapping gradients requiring tighter error control in order to control global errors. This feature may be common in cases where nearby trajectories are seen to diverge within the slow manifold over time.     

Nonlinear dynamics of the membrane potential of a bursting pacemaker cell

This article presents the results of an exploration of one two-parameter space of the Chay model of a cell excitable membrane. There are two main regions: a peripheral one, where the system dynamics will relax to an equilibrium point, and a central one where the expected dynamics is oscillatory. In the second region, we observe a variety of self-sustained oscillations including periodic oscillation, as well as bursting dynamics of different types. These oscillatory dynamics can be observed as periodic oscillations with different periodicities, and in some cases, as chaotic dynamics. These results, when displayed in bifurcation diagrams, result in complex bifurcation structures, which have been suggested as relevant to understand biological cell signaling.     

Noise-induced synchronous stochastic oscillations in small scale cultured heart-cell networks

This paper reports that the synchronous integer multiple oscillations of heart-cell networks or clusters are observed in the biology experiment.The behaviour of the integer multiple rhythm is a transition between super-and subthreshold oscillations,the stochastic mechanism of the transition is identified.The similar synchronized oscillations are theoretically reproduced in the stochastic network composed of heterogeneous cells whose behaviours are chosen as excitable or oscillatory states near a Hopf bifurcation point.The parameter regions of coupling strength and noise density that the complex oscillatory rhythms can be simulated are identified.The results show that the rhythm results from a simple stochastic alternating process between super-and sub-threshold oscillations.Studies on single heart cells forming these clusters reveal excitable or oscillatory state nearby a Hopf bifurcation point underpinning the stochastic alternation.In discussion,the results are related to some abnormal heartbeat rhythms such as the sinus arrest.