Modeling and Entraining Human Capability in Space
KeywordsMathematical models Simulations Desynchronization Performance Circadian
Space operations are extraordinarily challenging endeavors, demanding high cognitive performance and alertness from both astronauts and ground-based crew. Due to the nature of the space environment and mission constraints, it can be difficult to entrain, or align, the body’s internal ~24.2-h circadian rhythm to the required day length (e.g., the 24-h Earth day or the 24.65-h Mars day), to adapt to shifts in sleep/wake or work schedules, and to obtain sufficient sleep. Both circadian rhythms and sleep physiology significantly affect human performance, alertness, mood, and other physiology. To address these concerns, mathematical models of human circadian rhythms, sleep, performance, and alertness have been developed. These models can be used to predict how individuals will function on different schedules, to suggest strategies to improve performance, to entrain circadian rhythms, and to optimize the use of countermeasures such as light, naps, and pharmaceuticals. These models are also applicable to other settings where individuals face difficulties entraining or shifting their circadian rhythms, such as shift-work, or where performance failures present a high risk, such as aviation, healthcare, security, and transportation.
Mathematical models have been developed to describe the properties of the human circadian clock, its responses to light and other stimuli, and its contribution to human performance and alertness (Jewett and Kronauer 1999). Models have also been developed to describe human sleep patterns (Daan et al. 1984; Booth and Behn 2014) and responses to pharmaceuticals, such as caffeine (Puckeridge et al. 2011) and melatonin (Breslow et al. 2013). Combined models that include all of these factors allow detailed predictions of humans’ ability to entrain to different schedules, their cognitive performance, and the effectiveness of various countermeasures designed to promote entrainment or improve cognitive performance (Robinson et al. 2011). These models are extremely valuable in space operations, where circadian entrainment can be challenging to achieve and where high performance is critical to mission success.
The human circadian clock is an endogenous clock that generates daily rhythms in multiple aspects of physiology, including behavior, sleep, and performance. When an individual is shielded from all environmental time cues, including light and temperature cycles, they express circadian rhythms with a non-24-h period called their “intrinsic period.” Each individual has a different intrinsic period, usually within the range 23.5–24.7 h for healthy individuals (Duffy et al. 2011).
Environmental stimuli can “reset” the circadian clock by causing it to shift earlier (advance) or later (delay). The most effective stimulus for resetting the human circadian clock is light (Duffy and Czeisler 2009). Light exposure in the biological morning (i.e., around the time the circadian clock promotes awakening) causes the clock to advance, while light exposure in the early biological night (i.e., around the time the circadian clock promotes sleep) causes the clock to delay. A periodic stimulus can in some cases cause the circadian clock to “entrain,” meaning the circadian clock’s rhythm has a period (i.e., cycle duration) equal to the period of the stimulus. For example, most individuals on Earth express 24-h circadian rhythms, due to entrainment of their circadian clocks to the natural 24-h light/dark cycle. Failure to entrain can result in non-24-h sleep-wake disorder, wherein individuals are unable to maintain a schedule with 24-h period, instead losing or gaining time each day.
Four factors determine the effect of a light stimulus: (i) timing: the same stimulus given at different times in the circadian cycle can cause different magnitudes of advances or delays, (ii) duration: longer light exposure generates a larger effect, (iii) intensity or brightness: brighter light generates a larger effect; (iv) wavelength or color: for prolonged light exposure, blue/green light is most effective (Gooley et al. 2010). While long light pulses induce larger responses than short light pulses, there is a nonlinear dose response curve for light duration, with diminishing incremental response for light pulse duration. Similarly, there are diminishing incremental responses for brightness, due to a nonlinear dose response curve for brightness. A series of short, moderately bright light pulses interrupted by periods of darkness can thus be almost as effective as a continuous period of brighter light for shifting the clock. As discussed below, these dose response relationships are nonlinear and interactive, making models of the light response extremely valuable when assessing the feasibility of different light strategies for achieving entrainment.
Entrainment to a schedule is easier when the period of that schedule is close to the individual’s intrinsic circadian period and when the stimulus associated with it is strong. The theoretical limits of human circadian entrainment can be inferred from studies of the human response to pulses of light (e.g., Khalsa et al. 2003). These data predict a maximum theoretical range of about 22–27 h. However, this range may be greatly reduced by real-world constraints on time that can be spent near a bright light source, the need to sleep at times when the circadian clock is most sensitive to light (i.e., the biological night), and the amount of energy available for generating light.
Entrainment in Space
Humans in space face challenges maintaining entrainment to a 24-h day due to their unusual environments. Astronauts on the International Space Station (ISS) orbit the Earth approximately once every 90 min, resulting in an orbital light/dark cycle with the same period. This light pattern is unsuited to entraining the circadian clock. It may be important that astronauts on the same work shift are entrained to the same schedule, so that they may effectively work and socialize together. It is thus vital that that the light timing, duration, intensity, and wavelength on the ISS or other vehicles meet constraints on energy, time, visibility for work tasks, and the physiological limits of entrainment, which differ between individuals based on their intrinsic circadian periods or sensitivity to light.
The importance of carefully designing light schedules to achieve entrainment is demonstrated by the recent Mars-500 Mission, in which individuals were largely able to self-select their light exposure patterns within a 24.0-h scheduled day. One of the six crew members became desynchronized from the rest of the crew, with a ~25.0-h sleep/wake cycle, rather than a 24.0-h sleep/wake cycle. Another member of the crew had an abnormal circadian phase relationship with the sleep/wake cycle. Therefore, one-third of the crew on this mission did not have normally entrained circadian rhythms (Basner et al. 2013). This finding is consistent with early experiments in circadian biology that demonstrated humans tend to adopt an approximately 25-h sleep/wake cycle when allowed to fully self-select sleep schedules and light exposure patterns (Wever 1979). This occurs due to individuals preferentially selecting light exposure in their biological evening and night, leading to systematic delay of the circadian rhythm and/or an extension of the circadian period relative to the intrinsic period (Klerman et al. 1996). Desynchronization of crew members’ circadian rhythms from sleep/wake cycles could be detrimental for team cohesion and team effectiveness in a real mission.
Reentrainment after a sudden shift in time-zones is another challenge faced during space operations, with “jet-lag” being its Earth analog. Time-zone shifts can be caused by activities that must occur out of step with the daily schedule, such as activities constrained by orbital mechanics (e.g., arrival of another vessel). When these shifts occur, individuals are temporarily out of alignment with their new schedule, resulting in sleep loss and circadian misalignment. Since these factors greatly increase the risk of performance-based errors, achieving reentrainment as rapidly as possible is crucial. As discussed below, mathematical models have now been developed to find optimal light schedules for reentrainment.
Different challenges arise when individuals need to be entrained to a non-24-h schedule; in this case, a light pattern with the desired period may be used. One example is entrainment to the 24.65-h Mars day. Theoretically, this falls within the human range of entrainment. During the Phoenix Mars Lander mission, 87% of Earth-based crew were able to entrain to the Mars day, aided by the use of blue light boxes (Barger et al. 2012). However, it is easier for individuals with intrinsic periods close to 24.65 h to entrain to the Mars day. One study demonstrated that a lighting level of 100 lux during wakefulness is barely sufficient to entrain most individuals to a 24.65-h day, while a lighting level of 25 lux during wakefulness is insufficient to entrain individuals with relatively short intrinsic periods to that schedule (Gronfier et al. 2007).
An important secondary consideration for entrainment is achieving correct alignment of the circadian rhythm. If the light stimulus is only barely sufficient to achieve entrainment – either due to it being a weak stimulus or due to the individual being close to the edge of their theoretical range of entrainment – the circadian rhythm will be abnormally aligned, as was observed in both the 100 lux conditions and in the Mars-500 mission described above. Under these conditions, entrainment can only theoretically occur with the light stimulus positioned during the biological night, when the circadian clock is most sensitive to light. Consequently, the circadian clock is promoting sleep during light periods and promoting wakefulness during dark periods. This can lead to poor quality sleep and performance failures (Guo et al. 2014). Introducing brighter light can help to achieve correct circadian alignment. For example, the addition of two 45-min, 9500 lux light pulses to the 100 lux condition described above improved circadian alignment.
Models of Entrainment
The human circadian clock behaves like a self-sustaining oscillator with a stable limit cycle (a trajectory that repeats over time). The clock’s intrinsic period is the time it takes the oscillator complete one full cycle. When perturbed from the limit cycle, the oscillator returns to the limit cycle over time. Stimuli, including light, can cause the oscillator to advance or delay with respect to its original position on the limit cycle.
These models can be used to predict how the circadian clock will respond to a given light or activity schedule. Specifically, they can predict the shifts caused by particular light patterns, whether a light pattern will cause entrainment, the alignment of the entrained circadian rhythm relative to the light pattern, and the timing of key physiological markers, such as the core body temperature minimum and melatonin release. These variables are difficult to predict without models, due to the complex nature of the circadian clock’s response to light (described above). In space, where both time and power supply may be at a premium, it is extremely important to accurately account for these factors in designing light schedules.
Control theory can be used to optimize inputs to the circadian clock to achieve a desired goal. For example, mathematically optimal light patterns have been found for shifting the human circadian clock to a new time-zone in the minimum possible time (Dean et al. 2009; Serkh and Forger 2014). In principle, the same approach could be used to find optimal light patterns under multiple real-world constraints (e.g., time and power demands).
Models of Human Performance
The issues faced in space operations, including difficulties maintaining circadian entrainment, extended wake duration, and high cognitive performance, impact many other industries, including aviation, healthcare, security, and transportation. The models developed for space have thus also translated into outcomes on Earth. These have included model-driven strategies for improving shift-work schedules (Postnova et al. 2012).
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