Hopf bifurcations in multiple-parameter space of the Hodgkin-Huxley equations I. Global organization of bistable periodic solutions

 The Hodgkin-Huxley equations (HH) are parameterized by a number of parameters and shows a variety of qualitatively different behaviors depending on the parameter values. We explored the dynamics of the HH for a wide range of parameter values in the multiple-parameter space, that is, we examined the global structure of bifurcations of the HH. Results are summarized in various two-parameter bifurcation diagrams with I _ext (externally applied DC current) as the abscissa and one of the other parameters as the ordinate. In each diagram, the parameter plane was divided into several regions according to the qualitative behavior of the equations. In particular, we focused on periodic solutions emerging via Hopf bifurcations and identified parameter regions in which either two stable periodic solutions with different amplitudes and periods and a stable equilibrium point or two stable periodic solutions coexist. Global analysis of the bifurcation structure suggested that generation of these regions is associated with degenerate Hopf bifurcations. Received: 23 April 1999 / Accepted in revised form: 24 September 1999     

Periodic metabolic systems: Oscillations in multiple-loop negative feedback biochemical control networks

Summary For a general multiple loop feedback inhibition system in which the end product can inhibit any or all of the intermediate reactions it is shown that biologically significant behaviour is always confined to a bounded region of reaction space containing a unique equilibrium. By explicit construction of a Liapunov function for the general n dimensional differential equation it is shown that some values of reaction parameters cause the concentration vector to approach the equilibrium asymptotically for all physically realizable initial conditions. As the parameter values change, periodic solutions can appear within the bounded region. Some information about these periodic solutions can be obtained from the Hopf bifurcation theorem. Alternatively, if specific parameter values are known a numerical method can be used to find periodic solutions and determine their stability by locating a zero of the displacement map. The single loop Goodwin oscillator is analysed in detail. The methods are then used to treat an oscillator with two feedback loops and it is found that oscillations are possible even if both Hill coefficients are equal to one.     

Multiple limit cycles in predator-prey models

A series of one-predator one-prey models are studied using two parameter Hopf bifurcation techniques which allow the determination of two periodic orbits. The biological implications of the results, in terms of domains of attraction and multiple stable states, are discussed.     

The discrete Rosenzweig model

Discrete time versions of the Rosenweig predator-prey model are studied by analytic and numerical methods. The interaction of the Hopf bifurcation leading to periodic orbits and the period-doubling bifurcation is investigated. It is shown that for certain choices of the parameters there is stable coexistence of both species together with a local attractor at which the prey is absent.     

Effects of quarantine in six endemic models for infectious diseases

Thresholds, equilibria, and their stability are found for SIQS and SIQR epidemiology models with three forms of the incidence. For most of these models, the endemic equilibrium is asymptotically stable, but for the SIQR model with the quarantine-adjusted incidence, the endemic equilibrium is an unstable spiral for some parameter values and periodic solutions arise by Hopf bifurcation. The Hopf bifurcation surface and stable periodic solutions are found numerically.     

Quantitative analysis of the Hopf bifurcation in the Goodwin n-dimensional metabolic control system

We study, from a quantitative point of view, the Hopf bifurcation in an ODE model of feedback control type introduced by Goodwin (1963) to describe the dynamics of end-product inhibition of gene activity. We formally prove that the exchange of linear stability of the positive equilibrium in the n-dimensional Goodwin system with equal reaction constants coexists with a Hopf bifurcation of nontrivial periodic solutions emanating from this equilibrium, without any further restriction on the dimension n 3 or on the Hill coefficient . The direction of the bifurcation, and the stability and the period of the bifurcating orbits are estimated by means of the algorithm proposed by Hassard et al. (1981).Supported by MURST 40/60%     

Bifurcation of orbits and synchrony in inferior olive neurons

Inferior olive neurons (IONs) have rich dynamics and can exhibit stable, unstable, periodic, and even chaotic trajectories. This paper presents an analysis of bifurcation of periodic orbits of an ION when its two key parameters (a, μ) are varied in a two-dimensional plane. The parameter a describes the shape of the parabolic nonlinearity in the model and μ is the extracellular stimulus. The four-dimensional ION model considered here is a cascade connection of two subsystems (S(a) and S(b)). The parameter plane (a - μ) is delineated into several subregions. The ION has distinct orbit structure and stability property in each subregion. It is shown that the subsystem S(a) or S(b) undergoes supercritical Poincare-Andronov-Hopf (PAH) bifurcation at a critical value μ(c)(a) of the extracellular stimulus and periodic orbits of the neuron are born. Based on the center manifold theory, the existence of periodic orbits in the asymptotically stable S(a), when the subsystem S(b) undergoes PAH bifurcation, is established. In such a case, both subsystems exhibit periodic orbits. Interestingly when S(b) is under PAH bifurcation and S(a) is unstable, the trajectory of S(a) exhibits periodic bursting, interrupted by periods of quiescence. The bifurcation analysis is followed by the design of (i) a linear first-order filter and (ii) a nonlinear control system for the synchronization of IONs. The first controller uses a single output of each ION, but the nonlinear control system uses two state variables for feedback. The open-loop and closed-loop responses are presented which show bifurcation of orbits and synchronization of oscillating neurons.     

Transient oscillations induced by delayed growth response in the chemostat

In this paper, in order to try to account for the transient oscillations observed in chemostat experiments, we consider a model of single species growth in a chemostat that involves delayed growth response. The time delay models the lag involved in the nutrient conversion process. Both monotone response functions and nonmonotone response functions are considered. The nonmonotone response function models the inhibitory effects of growth response of certain nutrients when concentrations are too high. By applying local and global Hopf bifurcation theorems, we prove that the model has unstable periodic solutions that bifurcate from unstable nonnegative equilibria as the parameter measuring the delay passes through certain critical values and that these local periodic solutions can persist, even if the delay parameter moves far from the critical (local) bifurcation values.When there are two positive equilibria, then positive periodic solutions can exist. When there is a unique positive equilibrium, the model does not have positive periodic oscillations and the unique positive equilibrium is globally asymptotically stable. However, the model can have periodic solutions that change sign. Although these solutions are not biologically meaningful, provided the initial data starts close enough to the unstable manifold of one of these periodic solutions they may still help to account for the transient oscillations that have been frequently observed in chemostat experiments. Numerical simulations are provided to illustrate that the model has varying degrees of transient oscillatory behaviour that can be controlled by the choice of the initial data.Mathematics Subject Classification: 34D20, 34K20, 92D25Research was partially supported by NSERC of Canada.This work was partly done while this author was a postdoc at McMaster.     

Anti-control of periodic firing in HR model in the aspects of position,amplitude and frequency

This paper proposes a novel controller to control position, amplitude and frequency of periodic firing activity in Hindmarsh–Rose model based on Hopf bifurcation theory which is composed of linear control gain and nonlinear control gain. First, we select the activation of the fast ion channel as control parameter. Based on explicit criterion of Hopf bifurcation, a series of conditions are obtained to derive the linear gains of controller responsible for control of the location where the periodic firing activity occurs. Then, based on the control parameter, a series of conditions are obtained to derive the nonlinear gains of controller responsible for controlling the amplitude and frequency of periodic firing activity by using center manifold and normal form. Finally, the numerical experiments show that our controller can make the periodic firing activity occur at designed value and control the amplitude and frequency of periodic firing activity by adjusting nonlinear control gain of controller.     

Existence of traveling wave solutions in a diffusive predator-prey model

 We establish the existence of traveling front solutions and small amplitude traveling wave train solutions for a reaction-diffusion system based on a predator-prey model with Holling type-II functional response. The traveling front solutions are equivalent to heteroclinic orbits in R ⁴ and the small amplitude traveling wave train solutions are equivalent to small amplitude periodic orbits in R ⁴ . The methods used to prove the results are the shooting argument and the Hopf bifurcation theorem. Received: 25 May 2001 / Revised version: 5 August 2002 / Published online: 19 November 2002 RID="*" ID="*" Research was supported by the National Natural Science Foundations (NNSF) of China. RID="*" ID="*" Research was partially supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada. On leave from the Department of Mathematics and Statistics, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada. Mathematics Subject Classification (2000): 34C35, 35K57 Key words or phrases: Traveling wave solution – Wazewski set – Shooting argument – Hopf bifurcation Acknowledgements. We would like to thank the two referees for their careful reading and helpful comments.     

Persistence and periodic orbits of a three-competitor model with refuges.

We consider a model composed of four patches. One patch has three competing species forming a heteroclinic cycle within the patch. The remaining patches are refuges for the three competitors, and each species can diffuse between the competitive patch and its refuge. It is proved that the model can be made persistent by the introduction of the refuges for the competitors even if the isolated competitive patch has an attracting heteroclinic cycle. Further it is shown that Hopf bifurcation is possible when we change the value of the diffusion constant and periodic orbits may exist in a specific case.     

Modelling the spatio-temporal dynamics of multi-species host-parasitoid interactions: heterogeneous patterns and ecological implications

A mathematical model of the spatio-temporal dynamics of a two host, two parasitoid system is presented. There is a coupling of the four species through parasitism of both hosts by one of the parasitoids. The model comprises a system of four reaction-diffusion equations. The underlying system of ordinary differential equations, modelling the host-parasitoid population dynamics, has a unique positive steady state and is shown to be capable of undergoing Hopf bifurcations, leading to limit cycle kinetics which give rise to oscillatory temporal dynamics. The stability of the positive steady state has a fundamental impact on the spatio-temporal dynamics: stable travelling waves of parasitoid invasion exhibit increasingly irregular periodic travelling wave behaviour when key parameter values are increased beyond their Hopf bifurcation point. These irregular periodic travelling waves give rise to heterogeneous spatio-temporal patterns of host and parasitoid abundance. The generation of heterogeneous patterns has ecological implications and the concepts of temporary host refuge and niche formation are considered.     

Stability switches,oscillatory multistability,and spatio-temporal patterns of nonlinear oscillations in recurrently delay coupled neural networks

A model of time-delay recurrently coupled spatially segregated neural assemblies is here proposed. We show that it operates like some of the hierarchical architectures of the brain. Each assembly is a neural network with no delay in the local couplings between the units. The delay appears in the long range feedforward and feedback inter-assemblies communications. Bifurcation analysis of a simple four-units system in the autonomous case shows the richness of the dynamical behaviors in a biophysically plausible parameter region. We find oscillatory multistability, hysteresis, and stability switches of the rest state provoked by the time delay. Then we investigate the spatio-temporal patterns of bifurcating periodic solutions by using the symmetric local Hopf bifurcation theory of delay differential equations and derive the equation describing the flow on the center manifold that enables us determining the direction of Hopf bifurcations and stability of the bifurcating periodic orbits. We also discuss computational properties of the system due to the delay when an external drive of the network mimicks external sensory input.     

An SIS epidemic model with variable population size and a delay

The SIS epidemiological model has births, natural deaths, disease-related deaths and a delay corresponding to the infectious period. The thresholds for persistence, equilibria and stability are determined. The persistence of the disease combined with the disease-related deaths can cause the population size to decrease to zero, to remain finite, or to grow exponentially with a smaller growth rate constant. For some parameter values, the endemic infective-fraction equilibrium is asymptotically stable, but for other parameter values, it is unstable and a surrounding periodic solution appears by Hopf bifurcation.Research Supported in part by NSERC grant A-8965 and the University of Victoria Committee on Faculty Research & Travel     

Dynamics of Notch Activity in a Model of Interacting Signaling Pathways

Networks of interacting signaling pathways are formulated with systems of reaction-diffusion (RD) equations. We show that weak interactions between signaling pathways have negligible effects on formation of spatial patterns of signaling molecules. In particular, a weak interaction between Retinoic Acid (RA) and Notch signaling pathways does not change dynamics of Notch activity in the spatial domain. Conversely, large interactions of signaling pathways can influence effects of each signaling pathway. When the RD system is largely perturbed by RA-Notch interactions, new spatial patterns of Notch activity are obtained. Moreover, analysis of the perturbed Homogeneous System (HS) indicates that the system admits bifurcating periodic orbits near a Hopf bifurcation point. Starting from a neighborhood of the Hopf bifurcation, oscillatory standing waves of Notch activity are numerically observed. This is of particular interest since recent laboratory experiments confirm oscillatory dynamics of Notch activity.     

Biomass and biodiversity in species-rich tritrophic communities

We consider a tritrophic system with one basal and one top species and a large number of primary consumers, and derive upper and lower bounds for the total biomass of the middle trophic level. These estimates do not depend on dynamical regime, holding for fixed point, periodic, or chaotic dynamics. We have two kinds of estimates, depending on whether the predator abundance is zero. All these results are uniform in a self-limitation parameter, which regulates prey diversity in the system. For strong self-limitation, diversity is large; for weak self-limitation, it is small. Diversity depends on the variance of species’ parameter values. The larger this variance, the lower the diversity, and vice versa. Moreover, variation in the parameters of the Holling type II functional response changes the bifurcation character, with the equilibrium state with nonzero predator abundance losing stability. If that variation is small then the bifurcation can lead to oscillations (the Hopf bifurcation). Under certain conditions, there exists a supercritical Hopf bifurcation. We then find a connection between diversity and Hopf bifurcations. We also show that the system exhibits top-down regulation and a hump-shaped diversity-productivity curve.We then extend the model by allowing species to experience self-regulation. For this extended model, explicit estimates of prey diversity are obtained. We study the dynamics of this system and find the following. First, diversity and system dynamics crucially depend on variation in species parameters. We show that under certain conditions, the system undergoes a supercritical Hopf bifurcation. We also establish a connection between diversity and Hopf bifurcations. For strong self-limitation, diversity is large and complex dynamics are absent. For weak self-limitation, diversity is small and the equilibrium with non-zero predator abundance is unstable.     

Periodicity in an epidemic model with a generalized non-linear incidence

We develop and analyze a simple SIV epidemic model including susceptible, infected and perfectly vaccinated classes, with a generalized non-linear incidence rate subject only to a few general conditions. These conditions are satisfied by many models appearing in the literature. The detailed dynamics analysis of the model, using the Poincaré index theory, shows that non-linearity of the incidence rate leads to vital dynamics, such as bistability and periodicity, without seasonal forcing or being cyclic. Furthermore, it is shown that the basic reproductive number is independent of the functional form of the non-linear incidence rate. Under certain, well-defined conditions, the model undergoes a Hopf bifurcation. Using the normal form of the model, the first Lyapunov coefficient is computed to determine the various types of Hopf bifurcation the model undergoes. These general results are applied to two examples: unbounded and saturated contact rates; in both cases, forward or backward Hopf bifurcations occur for two distinct values of the contact parameter. It is also shown that the model may undergo a subcritical Hopf bifurcation leading to the appearance of two concentric limit cycles. The results are illustrated by numerical simulations with realistic model parameters estimated for some infectious diseases of childhood.     

An epidemiological model with a delay and a nonlinear incidence rate

An epidemiological model with both a time delay in the removed class and a nonlinear incidence rate is analysed to determine the equilibria and their stability. This model is for diseases where individuals are first susceptible, then infected, then removed with temporary immunity and then susceptible again when they lose their immunity. There are multiple equilibria for some parameter values, and, for certain of these, periodic solutions arise by Hopf bifurcation from the large nontrivial equilibrium state.Research supported in parts by Centers for Disease Control Contract 200-87-0515Research supported in part by NSERC A-8965     

Hopf bifurcation in three-species food chain models with group defense.

Three-species food-chain models, in which the prey population exhibits group defense, are considered. Using the carrying capacity of the environment as the bifurcation parameter, it is shown that the model without delay undergoes a sequence of Hopf bifurcations. In the model with delay it is shown that using a delay as a bifurcation parameter, a Hopf bifurcation can also occur in this case. These occurrences may be interpreted as showing that a region of local stability (survival) may exist even though the positive steady states are unstable. A computer code BIFDD is used to determine the stability of the bifurcation solutions of a delay model.     

Mathematical modelling of dynamics and control in metabolic networks: VI. Dynamic bifurcations in single biochemical control loops

A dynamic stability analysis of an extended form of the Goodwin equations is presented. The Goodwin equations are extended to include Michaelis-Menten kinetics for the removal of the end-product. Inclusion of saturation kinetic behavior substantially increases the likelihood of dynamic instability in this model control loop. Oscillations are found for reaction chains of low order, as low as second order, and low degrees of co-operativity, as low as v = 2, simultaneously, thus indicating that dynamic instability in this system exists for physiologically realistic parameter values. The branches of bifurcated solutions are computed numerically and unstable Hopf bifurcations are found. Further, solution branches from stable Hopf bifurcation points are found to "fold back", i.e. have periodic limit points, producing situations where multiple stable limit cycles exist.