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3.4 sleep

Assessment Of Sleep Dynamics In A
Simulated Space Station Environment
Lakshmi Putcha, Ph.D., Ram Nimmagudda, Ph.D.,
Chantal Rivera, Ph.D.
Based on prior experience, it is believed that the unique environmental condi- tions and work-rest schedules aboard orbital spacecraft (i.e., the International SpaceStation (ISS)) will result in sleep decrements and fatigue in astronauts. This reportdetails methods for estimating sleep variables and circadian rhythms in a simulatedwork-rest environment that mimics the schedule of ISS crew activities. Eighthealthy subjects in two separate studies stayed for 60 days (Phase IIa) and 91 days(Phase III) in a closed life support test facility at Johnson Space Center. Subjectswore an activity and ambient light monitor (Actillume™), completed sleep logstwice daily, and collected timed saliva and void-by-void urine samples for 48 hours.
This protocol was repeated four times during the 60-day chamber study and sixtimes during the 91-day study; results were compared with samples collectedbefore and after each chamber stay. Sleep variables (latency, duration and efficien-cy) were estimated from the Actillume™ data (objective) and from the sleep logs(subjective); acrophases for salivary melatonin and urinary melatonin sulfate weredetermined from concentration versus time profiles. Objective assessment of sleepefficiency, sleep duration and sleep latency were lower than the corresponding sub-jective assessments. In addition, the number of awakenings recorded by actigraphywas higher than those from the subjective sleep log scores. There were no signifi-cant differences in sleep variables between baseline and chamber stay periods.
Changes in sleep variables were independent of chamber stay duration. Self-assess-ment of sleep quality scores did not reflect any sleep decrements. Wake period light intensity in the chamber was lower (50 -100 lux) compared to baseline readings(1000 -1500 lux). Salivary melatonin acrophase was delayed during the chamberstay by 2.7 hours and compared well with the urinary melatonin sulfate acrophase,which was delayed 3.0 hours. The chamber light conditions were similar to thoseof ISS and may be responsible for the melatonin acrophase delays noted during thechamber study. These results indicate that the methods tested here will be sufficiently sensitive to detect sleep decrements and contributing circadian rhythmchanges in astronauts aboard ISS. Salivary melatonin levels could serve as a sensitive marker of determining circadian rhythmicity.
Assessment Of Sleep Dynamics In A Simulated Space Station Environment INTRODUCTION
Potential disturbances of circadian rhythmicity in the space flight environment and consequent decrements in performance efficiency and in the well-being ofastronauts are major concerns of NASA. In addition to changes in environmentalfactors, such as the absence of a gravity vector and ultra-shortened light-darkcycles, other factors that contribute to the development of sleep disturbances andfatigue during space flights include the abnormal length of working periods (highwork load effect), continuous deviation of the sleep-wake cycle duration from 24 hours (‘migrating day’) effect, and cyclic noise disturbances.
With respect to sleep during space flight, a continuous reduction of sleep time and an increase in sleep latency were reported from earlier missions (6) and morepronounced sleep disturbances were reported with dual-shift crews (5, 12). Resultsof a simulation study reflecting the schedule of work-rest periods indicate a distinctincrease in awake time as well as a decline of the sleep efficiency index and adescynchrony of circadian rhythms (7, 18). In a more recent study (16) that analyzed crew sleep patterns on Shuttle missions, decreased sleep duration andincreased use of sleep medications during dual-shift missions compared to thoseused on single-shift flights was reported. In an even more recent investigation (14),in-flight use of medications from astronaut debriefings after 79 U.S. Space Shuttlemissions was evaluated. From the 219 records obtained, 45% reported usage ofmedications for sleep disturbances. Furthermore, sleep medications were less efficacious and were therefore administered for longer periods of time (4, 14). Inaddition to these physiological and sleep disturbances, in order to meet operationaldemands, crewmembers have been assigned shift-work schedules during certaindual-shift missions. It is well documented that sleep deficits, biological asynchrony with work-rest activities, and sleep-promoting medications will impact alertness and inducefatigue (2). This presents a very high risk for shuttle and ground-operations of thespace program and, particularly to crew health and safety. Current strategies forminimizing sleep decrements due to shift-work during flights are based on the theory that exposure to bright light aids shift workers by altering or re-orientingtheir circadian rhythms (17). To better prepare the subjective night-shift crew andto support launch and landing time activities, crewmembers are entrained to matchtheir work schedules to their sleep-wake activities using artificial light and simultaneous sleep shift schedules. Limited data have been collected from theseastronauts before flight, during the light assisted sleep-shifting period in the daysjust before flight, and immediately after flight (19). In this study salivary melatoninand cortisol rhythms were examined to determine the effectiveness of this entrain-ment protocol in accomplishing the desired shifting of the endogenous rhythms to match in-flight work-rest activities. Results of this investigation indicated that Assessment Of Sleep Dynamics In A Simulated Space Station Environment targeted shifts were achieved for both cortisol and melatonin rhythms before flightand were restored immediately after return to Earth. However, ambient light levelson the Shuttle were low and may have been insufficient for circadian entrainment.
In order to augment sleep quality, pharmacological agents are often prescribed during flight, in addition to pre-flight entrainment. However, a systematic evaluation ofthe effectiveness of light treatment on the maintenance of in-flight work-rest demandsis missing due to a lack of methods and technologies that are both sufficiently sensitiveand flight-suitable. To fill this gap, the present study was conducted to evaluate objective and subjective data collection methods for sleep quality and contributing variables in a ground-based analog environment in human subjects confined to a closedchamber during as part of Phase IIa and Phase III Lunar Mars Life Support Test Project(LMLSTP). Information gained from this study will be useful in the identification andvalidation of sensitive, non-obtrusive techniques for evaluating sleep and circadianrhythms during space flight.
METHODS AND MATERIALS
Experimental Design
All procedures involving human subjects for this study were reviewed and approved by the Johnson Space Center Institutional Review Board. The test group consisted of eight subjects, three females and five males, from two separate phases ofchamber confinement (Phase IIa and Phase III). Each phase consisted of one pre-chamber, four (Phase IIa) or six (Phase III) in-chamber and one post-chamber data collection session. Each session was 48 hours long during which the following activi-ties were performed by the crewmembers: An Actillume™ was worn on the wrist of the non-dominant arm of each crew member for 48 hours. The activity data recorded by the Actillume™ were autoscoredfor sleep, while the illumination data were analyzed for patterns of light exposure.
An electronic sleep/wake questionnaire was completed upon wake up and before bedtime using the Ames Interactive Reporting Log (AIRLOG). AIRLOG is a tooldeveloped exclusively for research in aviation and ground transportation environ-ments; the instrument was developed by NASA Ames Research Center andincludes separate components that relate to the events of the day preceding the sleepperiod, the quality of sleep period, and the ensuing wake time. These data were analyzed to estimate subjective changes in sleep duration, latency, efficiency andquality during chamber stay. Saliva samples were collected every two hours while subjects were awake using salivettes (Sarstedt, Inc., Newton, NC). Void-by-void urine samples were also collected during the 48-hour period. All saliva and urine samples were processedand stored at -40˚C until analysis. Samples were analyzed using commercial RIAkits to determine levels of melatonin and melatonin sulfate.
Assessment Of Sleep Dynamics In A Simulated Space Station Environment Data Analysis
Illumination data from the Actillume™ were analyzed for patterns and intensity of light exposure using vendor provided Action-3 software. Activity data were analyzed using Action-3 software using both the manual and autoscore options inthe software to estimate objective sleep variables.
Data from the AIRLOG were analyzed to estimate subjective sleep quality, efficiency and latency. Salivary melatonin concentrations were determined using commercially available direct radioimmunoassay kit (ALPCO). Urine aliquotswere assayed to determine 6-hydroxymelatonin sulfate levels by the method ofAldhous and Arendt (1).
Cosinor and cross-correlation methods were used to analyze salivary melatonin and urinary melatonin sulfate measurement data with respect to time (11). Cosinor analy-sis was based on least-squares fit of the cosine function to a series of observations. Thistechnique allowed characterization of the mesor (the 48-hour time-series mean),acrophase (peak time, referenced to local midnight) and amplitude (half of the peak-to-trough variability). Phase shifts were calculated from the entire 48-hour session bysubtracting the baseline acrophase from the in-chamber acrophase.
Objective measurements of sleep variables by Actillume™ showed no statistically significant differences between baseline (pre- and post-chamber) and in-chamber peri-ods. These data suggest that crewmembers adjusted with the Space Station analogwork-rest activities (Table 3.4-1). Light intensity during waking periods in the cham-ber was lower compared to baseline readings (Figure 3.4-1). Similar readings of lightintensity have been observed on two earlier space flight missions as well (15).
Self assessment of sleep variables (sleep latency, number of awakenings, sleep duration and sleep efficiency) by AIRLOG showed no changes between chamberstay and baseline (Table 3.4-1). In addition, sleep quality scores did not reflect anysleep decrements during chamber stays. A comparison of the sleep variables data from the objective and subjective scores indicate that subjective assessment scores of sleep by the crewmembers were higherthan the respective objective measures derived from actigraphy. This observation con-firms the general notion among sleep researchers that perception of sleep decrementsis always less than actual deficits. Sleep diaries have been used extensively in clinicaland research environments to evaluate subjective sleep quality (10). Subjective sleepscores are also useful in linking circadian parameter estimates (e.g. acrophase, mesor)with aspects of sleep quality and personality. It is necessary to assess sleep deficitsusing both subjective and objective data sets in order to identify any significantchanges in sleep hygiene that may adversely affect alertness and performance duringspace flight. Subjective estimates of sleep latency, duration and efficiency are ofteninadequate by the very nature of their being subjective, therefore, an objective estima- Assessment Of Sleep Dynamics In A Simulated Space Station Environment tion of these variables, such as actigraphy data, in conjunction with the subjective sleeplogs may provide a more comprehensive assessment of sleep hygiene in space. Resultsfrom this study indicate that the methods tested here are suitable for in-flight assessmentof sleep during long-duration flights. Non-obtrusive wrist-actigraphy appears to be avaluable diagnostic method for the assessment of sleep decrements in astronauts.
It is well known that rectal temperature and urine melatonin sulfate are good indices for determining circadian rhythmicity (3,13). Due to the inconveniencecaused by rectal probes during space flight, this is not a preferred means of data col-lection for astronauts. Although urine sample collection is non-invasive, it placesincreased demands on spacecraft stowage. Earlier reports indicated that there is goodcorrelation between salivary melatonin and serum melatonin levels suggesting thatsalivary melatonin rhythm is an accurate predictor of circadian rhythmicity (8).
Cosinor analysis of salivary melatonin and urinary melatonin sulfate excretion ratesfrom the present study yielded valuable information on the applicability of salivarydata for the assessment of circadian rhythms. When circadian variables derived fromboth markers are in agreement, acrophase estimates calculated from time profiles ofboth markers and an accepted measure of circadian shifts, are also in agreement(Figure 3.4-2). Regression analysis of these data indicated that good correlation existsbetween estimates from the two sets of data (Figure 3.4-3; r = 0.79). However, thecorrelation between delayed salivary melatonin rhythm and sleep duration, althoughweak (r =0.42) suggests that the desynchronized melatonin rhythm and sleep periodmay have affected the sleep quality in the chamber crewmembers as depicted byreduced sleep duration (Figure 3.4-4). These results suggest that salivary melatoninrhythms may be successfully employed for estimating circadian rhythms and relatedsleep decrements in astronauts during space missions. Further analysis of these datais in progress to evaluate the correlation between temperature and salivary melatoninrhythms; results from these analyses may confirm that salivary melatonin can be utilized as a reliable chronotherapeutic marker in place of temperature.
ACKNOWLEDGMENTS
We express our sincere appreciation to the staff of the LMLSTP Project Office for their support of this study. The authors also wish to thank the crewmembers fortheir compliance and enthusiastic participation in the study. We also thank Ms. Ladonna Miller from the Space and Life Sciences office for coordinating thestudy. We are grateful to Dr. Mark Rosekind for making AIRLOG, the hand heldsleep diary developed at the Ames Research Center, available for the study.
Assessment Of Sleep Dynamics In A Simulated Space Station Environment Table 3.4-1 Sleep variables in chamber crewmembers*
Objective
Subjective
Measurements Measurements
Baseline Chamber
Baseline Chamber
% Efficiency 88.50 ± 1.44 88.10 ± 1.73 96.40 ± 1.16 95.66 ± 1.03Latency (h) 0.27 ± 0.06 *Values are Mean ± SEM of 8 subjects**Wake after sleep onset Illumination
Baseline
In-Chamber
Figure 3.4-1 Light Exposure During Wake Period
Assessment Of Sleep Dynamics In A Simulated Space Station Environment Salivary Melatonin
Urinary MTS

Acrophase
(hours after midnight)
Baseline
In-Chamber
Figure 3.4-2 Comparative Estimates of Circadian Rhythm Changes
y= -2.3603+0.92814x Rˆ2=0.790
Acrophase
Salivary Melatonin
Urinary MTS Acrophase
Figure 3.4-3 Correlation between Urinary MTS and Salivary Melatonin Acrophases
Assessment Of Sleep Dynamics In A Simulated Space Station Environment y= 7.6255-0.21852x Rˆ2=0.427
Sleep Duration (h)
Subjective Assessment
Salivary Melatonin
(Acrophase)
Figure 3.4-4 Correlation of Rhythm Markers (Salivary Melatonin Acrophase)
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