Optimal Schedules of Light Exposure for Rapidly Correcting Circadian Misalignment

Jet lag arises from a misalignment of circadian biological timing with the timing of human activity, and is caused by rapid transmeridian travel. Jet lag's symptoms, such as depressed cognitive alertness, also arise from work and social schedules misaligned with the timing of the circadian clock. Using experimentally validated mathematical models, we develop a new methodology to find mathematically optimal schedules of light exposure and avoidance for rapidly re-entraining the human circadian system. In simulations, our schedules are found to significantly outperform other recently proposed schedules. Moreover, our schedules appear to be significantly more robust to both noise in light and to inter-individual variations in endogenous circadian period than other proposed schedules. By comparing the optimal schedules for thousands of different situations, and by using general mathematical arguments, we are also able to translate our findings into general principles of optimal circadian re-entrainment. These principles include: 1) a class of schedules where circadian amplitude is only slightly perturbed, optimal for dim light and for small shifts 2) another class of schedules where shifting occurs along the shortest path in phase-space, optimal for bright light and for large shifts 3) the determination that short light pulses are less effective than sustained light if the goal is to re-entrain quickly, and 4) the determination that length of daytime should be significantly shorter when delaying the clock than when advancing it.Author Summary: When our body's internal timekeeping system becomes misaligned with the time of day in the outside world, many negative effects can be felt, including decreased performance, improper sleep, and jet lag. When misalignment is prolonged, it can also lead to serious medical conditions, including cancer, cardiovascular disease, and possibly even late-onset diabetes. Rapid readjustment of our internal daily (circadian) clock by properly timed exposure to light, which is the strongest signal to our internal circadian clock, is therefore important to the large proportion of the population which suffers from misalignment, including transmeridian travelers, shift workers, and individuals with circadian disorders. Here we develop a methodology to determine schedules of light exposure which may shift the human circadian clock in the minimum time. By calculating thousands of schedules, we show how the human circadian pacemaker is predicted to be capable of shifting much more rapidly than previously thought, simply by adjusting the timing of the beginning and end of each day. Schedules are summarized into general principles of optimal shifting, which can be applied without knowledge of the schedules themselves.