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Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral Performance During Extended-Duration Spaceflight

Principal Investigator:
Charles A. Czeisler, Ph.D., M.D.

Harvard - Brigham and Women's Hospital

An exploration mission to Mars will require crewmembers to adapt to a 24.65-hour day throughout their stay on the planet. The ability of astronauts to perform well during the mission will be critically dependent upon adaptation of their circadian pacemaker to the longer day. Dr. Charles A. Czeisler hypothesizes that the longer day will cause the body to produce the sleep-promoting hormone melatonin during the waking day, impairing alertness and performance. Preliminary data reveal that intermittent bright light exposure is effective in maintaining entrainment of the circadian pacemaker to longer-than-24 hour days. Dr. Czeisler is testing a countermeasure of blue-enriched light to entrain the human circadian pacemaker to a 24.65-hour day. The results of the proposed studies will answer fundamental questions on the mechanisms underlying circadian entrainment in humans and could have a profound effect on the health, productivity and safety of astronauts during an exploration-class mission to Mars.

NASA Taskbook Entry

Technical Summary

The success of human exploration missions outlined in the goals for the Vision for Space Exploration and in the Global Exploration Strategy and Lunar Architecture announcement will depend on the crew's ability to remain alert and vigilant while operating sophisticated equipment and following complex procedures. Unfortunately, space exploration often involves disruptions to planned sleep-wake schedules and/or a non-24 hr sleep-wake schedule during these missions. This can impair circadian entrainment to the subsequent sleep-wake cycle, which results in sleep impairment, endocrine disturbance, and impaired daytime alertness and neurobehavioral function.

Our data suggest that most astronauts would exhibit circadian misalignment in the spaceflight lighting conditions of <25 lux on the windowless middeck of the space shuttle. Preliminary data from our laboratory reveal that intermittent bright light exposure is effective in maintaining entrainment of the circadian pacemaker to longer than 24 hour days. Other preliminary results demonstrate that blue light (~460 nm wavelength) is more efficient than white light or green light (~555 nm wavelength) of equal photon density in resetting the human circadian pacemaker. Given that bright light pulses might not be of practical use on the lunar or Martian habitats due to time and energy constraints these results demonstrate the need to develop practical and cost-effective countermeasures for addressing the challenges to the human circadian pacemaker during space missions.

When the current grant was submitted in 2003, we originally proposed to test a countermeasure of blue-enriched light to entrain the human circadian pacemaker to a 24.65 hour day. Specifically, we proposed to test the following hypotheses: 1) that synchronization of the human circadian pacemaker to a 24.65 hour day initiated at an adverse phase will not be appropriate in the presence of ~100 lux of white light; 2) that inappropriate circadian synchronization will result in the secretion of the sleep-promoting hormone melatonin during wake time, abnormal somatotropic and corticotropic activity, disturbed sleep, and impaired performance and daytime alertness and; 3) that exposure to blue-enriched light during the daytime will establish a normal entrained circadian phase in subjects scheduled to a 24.65 hour day.

Seven healthy subjects participated in a 71 day inpatient protocol consisting of 3 baseline days (16:8 hour wake:sleep) followed by 60 experimental days (24.65 hour, 16.43:8.22 hour). Light intensity during the experimental days was ~100 lux (n=2) and ~50 lux (n = 5) at 137 cm height in the horizontal angle. Circadian phase was measured by the Dim Light Melatonin Onset (DLMO) measured 6 times under dim light (~1.8 lux at 137 cm height in the horizontal angle) and postural control (before and after the experimental days, and on experimental days 6, 20, 34, and 48) and during several segments on the experimental days. The critical manipulation in the study was the timing of sleep on the first experimental day was shifted 12 hour compared to baseline; equivalent to a slam shift. To assess entrainment, phase angle was calculated from the difference between DLMO and scheduled bedtime.

The results showed that the average phase angle for subjects on the first 24.65 hour day was 12.5 + .26 hours for the 50 lux group and 8.96 + .96 hours for the 100 lux group, which is indicative of acute circadian misalignment. The average phase angle on the sixth experimental day was 5.8 + 1.6 hours for the 50 lux group and 7 + 3.7 hours for the 100 lux group, showing that subjects continued to be misaligned. The average phase angle on the 15th experimental day was 1.5 + .46 hours, after which they stabilized. The average phase angle was 2.4 + .31 hours on experimental day 34 and 2.2 + .26 hours on experimental day 48 (p>.05). The analysis of the cognitive data under these conditions is ongoing.

It is important to note the following: First, our results showed that crew members would be most vulnerable to the detrimental effects of circadian misalignment during the first two weeks of a mission. This is important, because the duration of short-term mission such as those to the ISS and the moon are approximately two weeks long. Second, the data reveal that light intensities that are similar to the lighting conditions during spaceflight are insufficient to induce rapid entrainment during a short-term mission. Therefore, we concluded that it was critical to develop countermeasures that would facilitate sleep and circadian adaptation rapidly. We refocused our research efforts on the circadian and sleep-wake challenges associated with short-duration lunar exploration. To do so, we modified our studies during the remainder of this grant period to explore this initial period of vulnerability further and test the effectiveness of our proposed countermeasure (blue-enriched light) in short-term missions.

The progress toward developing the blue light countermeasures is moving forward with the continuing work on the modified 12-day protocol. We have completed 6 subjects in the protocol, have 2 subjects currently in the laboratory, and several subjects who are being screened into the protocol. In the coming year, we plan to complete data collection and the analysis of the physiological and neurobehavioral data.

With the planned short-term missions outlined in the Global Exploration Strategy and Lunar Architecture announcement, it is vital to mission success to understand the limits of human performance under spaceflight conditions and develop countermeasures for ensuring health, productivity and safety of astronauts. With the current project, aimed at evaluating the effectiveness of blue-enriched light for circadian misalignment during planned space missions, we expect to provide NASA with a countermeasure which could be incorporated into the design specifications for planned lunar sorties and in the design of the polar lunar base.


Earth Applications

The purpose of the proposed studies was to test three specific hypotheses aimed at evaluating the effectiveness of blue-enriched light exposure over white light as a countermeasure for circadian misalignment during exploration class mission. Results from previous studies in our lab indicate exposure to blue-enriched light will be a more effective means of entraining the human circadian pacemaker compared to exposure to white light of similar photon density, or even to light of greater photon density but of inappropriate spectral content (long wavelengths, as on Mars). The funded research project has important implications for Earth-based applications, particularly in the development of treatment for circadian rhythm disorders. This project holds the potential for producing shorter, more efficient light treatment regimens, which would not only increase compliance in clinical populations (e.g. night-shift workers, people with Advanced and Delayed Sleep Phase Syndromes), but would make light treatment more practical in industrial/work settings.

This project's funding ended in 2008