Entrainment dynamics organised by global manifolds in a circadian pacemaker model

This is the final version. Available on open access from Frontiers Media via the DOI in this recordCircadian rhythms are established by the entrainment of our intrinsic body clock to periodic forcing signals provided by the external environment, primarily variation in light intensity across the day/night cycle. Loss of entrainment can cause a multitude of physiological difficulties associated with misalignment of circadian rhythms, including insomnia, excessive daytime sleepiness, gastrointestinal disturbances, and general malaise. This can occur after travel to different time zones, known as jet lag; when changing shift work patterns; or if the period of an individual’s body clock is too far from the 24-hour period of environmental cycles. We consider the loss of entrainment and the dynamics of re-entrainment in a two-dimensional variant of the Forger-Jewett-Kronauer model of the human circadian pacemaker forced by a 24-hour light/dark cycle. We explore the loss of entrainment by continuing bifurcations of one-to-one entrained orbits under variation of forcing parameters and the intrinsic clock period. We show that the severity of the loss of entrainment is dependent on the type of bifurcation inducing the change of stability of the entrained orbit, which is in turn dependent on the environmental light intensity. We further show that for certain perturbations, the model pblackicts a counter-intuitive rapid re-entrainment if the light intensity is sufficiently high. We explain this phenomenon via computation of invariant manifolds of fixed points of a 24-hour stroboscopic map and show how the manifolds organise re-entrainment times following transitions between day and night shift work.Medical Research Council (MRC)US-UK Fulbright CommissionEngineering and Physical Sciences Research Council (EPSRC)National Science Foundation (NSF