Robustness of Optimal Circadian Rhythm Entrainment under Model Perturbation.

The optimal circadian rhythm entrainment problem has been studied based on mathematical models, e.g. the Kronauer model. In this paper, we study the robustness of light-based circadian rhythm entrainment under model parameter perturbations as well as propose a feedback control law to improve the robustness of the entrainment strategy. Our study finds the model parameter whose perturbations affect the entrainment the most. We also find that feedback control reduces the sensivitity of the entrainment process to model parameter perturbations.Clinical relevance- Circadian misalignment has negative impacts on health, such as higher risks of cardiovascular disease and cancer. We present a numerical study of how well optimized circadian rhythm entrainment plans that are derived from a generic mathematical model work on personalized cases.