Numerical study of entrainment of the human circadian system and recovery by light treatment

Soon Ho Kim,Segun Goh,Kyungreem Han,Jong Won Kim,Mooyoung Choi

doi:10.1186/s12976-018-0077-x

Abstract

BackgroundWhile the effects of light as a zeitgeber are well known, the way the effects are modulated by features of the sleep-wake system still remains to be studied in detail.MethodsA mathematical model for disturbance and recovery of the human circadian system is presented. The model combines a circadian oscillator and a sleep-wake switch that includes the effects of orexin. By means of simulations, we characterize the period-locking zone of the model, where a stable 24-hour circadian rhythm exists, and the occurrence of circadian disruption due to both insufficient light and imbalance in orexin. We also investigate how daily bright light treatments of short duration can recover the normal circadian rhythm.ResultsIt is found that the system exhibits continuous phase advance/delay at lower/higher orexin levels. Bright light treatment simulations disclose two optimal time windows, corresponding to morning and evening light treatments. Among the two, the morning light treatment is found effective in a wider range of parameter values, with shorter recovery time.ConclusionsThis approach offers a systematic way to determine the conditions under which circadian disruption occurs, and to evaluate the effects of light treatment. In particular, it could potentially offer a way to optimize light treatments for patients with circadian disruption, e.g., sleep and mood disorders, in clinical settings.

Highlights

While the effects of light as a zeitgeber are well known, the way the effects are modulated by features of the sleep-wake system still remains to be studied in detail
The suprachiasmatic nucleus (SCN) located in the hypothalamus is the central pacemaker for circadian rhythms [2]
Period locking zone We study the dynamics of the model by means of simulations, employing the 4thorder Runge-Kutta method

Summary

Introduction

While the effects of light as a zeitgeber are well known, the way the effects are modulated by features of the sleep-wake system still remains to be studied in detail. The suprachiasmatic nucleus (SCN) located in the hypothalamus is the central pacemaker for circadian rhythms [2]. The SCN has a self-sustained, endogenous near-24 h period and gives cues to various functions of the body, acting as the master clock of the brain. The SCN is involved in the timing of the sleep-wake cycle, and applies increasing sleep pressure as the clock approaches subjective night [3]. The SCN adjusts its phase in response to the environment and is entrained to the daily cycle. The primary environmental cue that influences the phase of the SCN is the light-dark cycle. With daily adequate exposure to light, the entrained SCN ensures that we are active during the day and at rest during the night [6, 7]. The SCN along with the monoamine nucleus (MA), ventrolateral preoptic nucleus (VLPO), homeostatic regulators including adenosine, and orexenergic (ORX) neurons interact to consolidate a stable 24-h sleep-wake cycle [3, 8,9,10,11]

Methods

Results

Conclusion