Changes in the criticality of Hopf bifurcations due to certain model reduction techniques in systems with multiple timescales

A major obstacle in the analysis of many physiological models is the issue of model simplification. Various methods have been used for simplifying such models, with one common technique being to eliminate certain 'fast' variables using a quasi-steady-state assumption. In this article, we show when such a physiological model reduction technique in a slow-fast system is mathematically justified. We provide counterexamples showing that this technique can give erroneous results near the onset of oscillatory behaviour which is, practically, the region of most importance in a model. In addition, we show that the singular limit of the first Lyapunov coefficient of a Hopf bifurcation in a slow-fast system is, in general, not equal to the first Lyapunov coefficient of the Hopf bifurcation in the corresponding layer problem, a seemingly counterintuitive result. Consequently, one cannot deduce, in general, the criticality of a Hopf bifurcation in a slow-fast system from the lower-dimensional layer problem.