Research Article: Taking the Lag out of Jet Lag through Model-Based Schedule Design

Date Published: June 19, 2009

Publisher: Public Library of Science

Author(s): Dennis A. Dean, Daniel B. Forger, Elizabeth B. Klerman, Karl J. Friston

Abstract: Travel across multiple time zones results in desynchronization of environmental time cues and the sleep–wake schedule from their normal phase relationships with the endogenous circadian system. Circadian misalignment can result in poor neurobehavioral performance, decreased sleep efficiency, and inappropriately timed physiological signals including gastrointestinal activity and hormone release. Frequent and repeated transmeridian travel is associated with long-term cognitive deficits, and rodents experimentally exposed to repeated schedule shifts have increased death rates. One approach to reduce the short-term circadian, sleep–wake, and performance problems is to use mathematical models of the circadian pacemaker to design countermeasures that rapidly shift the circadian pacemaker to align with the new schedule. In this paper, the use of mathematical models to design sleep–wake and countermeasure schedules for improved performance is demonstrated. We present an approach to designing interventions that combines an algorithm for optimal placement of countermeasures with a novel mode of schedule representation. With these methods, rapid circadian resynchrony and the resulting improvement in neurobehavioral performance can be quickly achieved even after moderate to large shifts in the sleep–wake schedule. The key schedule design inputs are endogenous circadian period length, desired sleep–wake schedule, length of intervention, background light level, and countermeasure strength. The new schedule representation facilitates schedule design, simulation studies, and experiment design and significantly decreases the amount of time to design an appropriate intervention. The method presented in this paper has direct implications for designing jet lag, shift-work, and non-24-hour schedules, including scheduling for extreme environments, such as in space, undersea, or in polar regions.

Partial Text: Endogenous circadian (∼24 hour) rhythms are important physiological regulators of sleep quality and duration, hormone levels, mood (including alertness), and cognitive neurobehavioral performance in humans [1]. The significant effect of circadian timing (phase) on performance has been shown experimentally (e.g., [2]–[6] and in epidemiologic studies of accidents [7]–[17]. Changes in light exposure, sleep-wake patterns, and circadian rhythms associated with jet lag, space travel, and some work schedules have profound effects on multiple physiologic systems, including performance [1], [18]–[23]. The phase and amplitude of endogenous circadian rhythms, generated by a self-sustained pacemaker in the hypothalamus, are affected by ocular light stimuli [24],[25]. Therefore light stimuli have been used to shift the circadian pacemaker to be aligned with a new sleep-wake schedule, resulting in an increase in subjective alertness and objective performance at desired times compared with schedules without properly timed light pulses [2],[26].

The primary contribution of this work is an efficient and practical approach to designing re-entrainment schedules that uses both a novel schedule representation (schedule building blocks) and a novel algorithm for locating optimal solutions (circadian adjustment method, CAM). Our algorithm provides advantages over existing circadian schedule design techniques that evaluate a large number of schedules (genetic algorithms, enumeration) or use existing optimization techniques (Nelder-Mead, gradient descent, optimal control theory). Enumeration of all possible schedules quickly becomes computationally intractable as the number of days in the schedule increases. Existing optimization techniques are generally formulated to extract one solution that may be unrealistic in the operational setting. Our algorithm has been designed specifically to allow for multiple solutions to be determined through the specification of design and optimization parameters. The schedule design parameters (i.e. light level, light duration, sleep length) allow for families of schedules to be considered, which is analogous to facilitating constrained enumeration through the use of schedule building blocks. Consequently, a key contribution of the method is the integration of the schedule representation with an optimization approach, which gives the advantage of evaluating a large number of schedules with optimization, while reducing the drawbacks when each approach is used alone.