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Project Title:  Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness in Space Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 06/01/2008  
End Date: 09/30/2012  
Task Last Updated: 01/08/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Klerman, Elizabeth B. M.D., Ph.D. / Brigham and Women's Hospital/Harvard Medical Center 
Address:  Department of Medicine 
Division of Sleep Medicine 
Boston , MA 02115-5804 
Email: ebklerman@hms.harvard.edu 
Phone: 617-732-8145  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham and Women's Hospital/Harvard Medical Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Barger, Laura  Brigham and Women's Hospital 
Project Information: Grant/Contract No. NCC 9-58-HFP01603 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01603 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) BHP:Behavioral Health & Performance (archival in 2017)
Human Research Program Risks: (1) Sleep:Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload (IRP Rev F)
Human Research Program Gaps: (1) Sleep Gap 04:We need to identify indicators of individual vulnerabilities and resiliencies to sleep loss and circadian rhythm disruption, to aid with individualized countermeasure regimens, for autonomous, long duration and/or distance exploration missions (IRP Rev E)
(2) Sleep Gap 08:We need to develop individualized scheduling tools that predict the effects of sleep-wake cycles, light and other countermeasures on performance, and can be used to identify optimal (and vulnerable) performance periods during spaceflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date change to 9/30/2012 (from 5/31/2012) per NSBRI (Ed., 1/24/2012)

Task Description: Optimal levels of objective neurobehavioral performance, subjective alertness, and high-quality restorative sleep are critically important to astronaut and ground-based crew health and to the overall success of space missions. Neurobehavioral performance and alertness are affected by changes in circadian rhythms, homeostatic sleep/wake regulation, sleep inertia, and the interactions of these processes. Problems with sleep, circadian rhythms, and performance have been widely reported among astronauts and supporting ground crew. Therefore, it is imperative that work and sleep/wake schedules, including the timing of countermeasures such as light and naps, are designed to optimize individual performance, alertness, and sleep quality relative to operational requirements. Our approach is to use mathematical models to describe the underlying physiology of internal circadian timing, alertness, performance, and sleep to design effective countermeasures.

We have developed and validated three linked mathematical models: one of the human circadian pacemaker that includes the influence of light and of non-photic processes; one of performance and alertness that includes the effects of circadian rhythms, sleep/wake homeostasis, and sleep inertia; and one of the physiology underlying sleep/wake regulation. Together these models estimate and predict the effects of sleep/wake timing, light exposure, circadian phase, and some pharmaceuticals on performance and alertness. Performance and alertness measures are modeled independently to reflect differences in the underlying physiological processes and effects of sleep/wake on each measure. CPSS, the software that implements this model, has been used by NASA employees and NASA consultants to design light countermeasures for both astronaut pre-launch schedules and in-flight schedules.

Our specific aims were to: (1) Replace the current assumption that an individual sleeps the entire time when scheduled to sleep with probabilities of sleep and wake during scheduled sleep times; (2) Improve daily assessment of sleep and sleep disruption using actigraphy data; (3) Add statistical features including confidence limits to the predictions; (4) Update the software per astronaut and ground crew requests for specific features and reports. These projects address NASA's objectives to improve the design of individual countermeasures to reduce sleep disruption and improve performance and alertness in space and on Earth. As part of these overall goals, we published a novel scheduling algorithm called Shifter that automatically designs optimal light countermeasures for user-defined work and sleep schedules. Both experimental and field studies have shown that light interventions minimize fatigue while improving performance and sleep. This work required several mathematical and computational advances, including the development of a novel schedule representation and scheduling algorithm. The utility of this scheduling software extends beyond NASA-related schedules to include any operational setting that relies on work scheduled outside the typical 9am to 5pm shift, including night and rotating shift-work, transmeridian travel, and the design of work schedules for medical residents to improve performance and meet new national guidelines for restricted work hours.

To individualize model predictions, we are developing a statistical framework based on easily collected trait information (e.g., age, chronotype) that has been shown to correlate with differences in sleep timing, circadian phase, and performance and alertness. Although changes in physiology have been correlated with specialized questionnaire results (e.g., habitual sleep time is highly correlated with circadian phase), our current results suggest that a simple alteration of the model output using demographic information is not accurate. The work of Dr. Phillips (NSBRI post-doctoral fellow) has quantified mechanisms that may underlie individual differences in physiologically-determined sleep timing and self-reported chronotype (e.g., owl or lark ). The use of sleep aids during NASA missions is indicative of the difficulty with initiating and maintaining sleep that astronauts experience during space flight. To assess the ability of individuals to conform to scheduled work hours, Dr. Phillips has integrated the circadian and performance model with a model of the physiological mechanisms that control sleep/wake transitions. This combined model dynamically predicts whether an individual is awake or asleep across a simulated protocol and also allows for predictions of sleep efficiency and the likelihood of falling asleep during scheduled wake periods. This physiologically-based model can be readily extended to incorporate pharmaceutical effects. Using this model, we have now successfully incorporated the effects of melatonin and caffeine at different times and dosages.

Actigraphy is an inexpensive and less intrusive alternative to polysomnography and/or sleep/wake diaries to determine an individual's sleep/wake schedule. Prior iterations of the mathematical model relied on user input to generate sleep/wake schedules. Based on the work from this project, we can now use actigraphy to determine the actual sleep/wake schedule of an individual and use this information as input to our mathematical models. We recently completed a project in collaboration with two NSBRI investigators, Drs. Lockley and Barger. In this project, pattern recognition algorithms were used to identify the level of performance impairment in an individual based on a single session of neurobehavioral testing (rather than multiple hours of testing) under both controlled in-patient laboratory conditions and real world conditions, including during the NASA Phoenix Mars study. We continue to work with NASA and NSBRI personnel to meet their requests regarding use of the models and software.

Research Impact/Earth Benefits: The development of (1) mathematical models of circadian rhythms, sleep, alertness and performance, and (2) software based on these models to facilitate schedule design, can improve performance and alertness and thereby effectiveness and public safety for people who work at night, on rotating schedules, on non-24-hr schedules or on extended duty schedules (e.g., pilots, train and truck drivers, shift workers, health care workers, public safety officers). Attempting to sleep at adverse circadian phases is difficult, resulting in poor sleep efficiency. Similarly, attempting to work at adverse circadian phases and/or after a long time awake, results in poor worker performance and productivity, and leads to an increase in errors. For example, the accidents at the Chernobyl and Three Mile Island nuclear reactors and the Exxon Valdez grounding were all partially attributed to employees working at adverse circadian phases and the FAA reports of air traffic controllers sleeping while scheduled to work at night are related to their work schedule. The mathematical models and the available software that implements these models can be used to simulate and quantitatively evaluate different work and light exposure schedules to predict the expected circadian phase, subjective alertness and performance in an individual. Our software has been requested by members of academia, government and industry, including airline, safety, medical, and military applications. Its use could help produce improved work schedules for both astronauts and ground-crew. It is currently being used to evaluate potential work schedules for medical residents to improve performance while complying with new national work hour standards.

The previous model assumption that an individual sleeps the entire time that is available to them during a scheduled sleep episode has been improved by the recent incorporation of actigraphy as an input to the mathematical model of the actual sleep/wake times experienced by the individual. The use of actigraphy as a tool to record sleep has improved confidence levels on the daily assessment of sleep when compared to the use of sleep logs or diaries and also has reduced the user requirements for maintaining daily logs. The interface between actigraphy and the software enables faster and possibly more accurate predictions of circadian phase and performance parameters. The Shifter software now includes optimal countermeasure design, so that countermeasures can be planned for times of predicted poor performance and alertness. The schedule and countermeasure design program allows users to interactively design schedules and implement mathematically optimized light countermeasures (including intensity, duration and timing within the wake episode) to minimize worker fatigue. This scheduling software will be valuable to those who work at night, on rotating schedules, on non-24-hr schedules, or on extended duty schedules. The software allows individuals to design countermeasures for their assigned work schedules so that their sleep/ wake rhythms will be adjusted to ensure optimal performance at desired times, with respect to both scheduled work events and their circadian phase. Improving sleep duration and quality can also decrease the risk of accidents and errors, as well as decrease the long-term risks of cardiovascular, metabolic, immune, and psychological pathologies. We continue to work with NASA and NSBRI personnel to meet their requests regarding use of the models and software. We continue to work with Dr. Dorit Donoviel, Associate NSBRI Research Director, and Marti Fleming, NSBRI commercialization consultant, to promote commercialization of the work. The mathematical modeling efforts and software have also been used in educational programs and in the popular press to teach students and teachers about circadian rhythms and sleep and their effects on alertness and performance.

Task Progress & Bibliography Information FY2012 
Task Progress: Specific Aim 1 (predicting sleep/wake amounts within a scheduled sleep episode): We have integrated the existing circadian/performance model with a physiologically-based model of sleep/wake transitions. This integrated model can predict whether individuals are able to conform to enforced work schedules and includes estimates for the likelihood of insomnia during scheduled sleep periods or the likelihood that the individual will experience difficulty remaining awake during working hours. We have validated this integrated model against human data for caffeine and melatonin and we have related inter-individual differences in sleep timing (e.g., self-reported chronotype) to differences in the underlying physiology.

Specific Aim 2 (actigraphy): We have integrated the output from actigraphy software with the input required to run our Circadian Performance Simulation Software (CPSS). CPSS implements our mathematical model of the human circadian pacemaker, performance, and alertness, which includes the key processes of circadian rhythms, sleep/wake homeostasis, and sleep inertia on performance and alertness, as well as the effects of light on circadian rhythms. Pre-processing tools were developed to generate the sleep/wake schedule and light levels from either raw or processed actigraphy data. We have tested the ability to use outpatient actigraphy as input to CPSS to predict circadian phase for individuals under circadian entrained and phase-shift conditions.

Specific Aim 3 (Statistical modeling of individual circadian, sleep, performance, and alertness parameters): We have concentrated on statistical modeling of individual parameters of our circadian, performance, and alertness models. By fitting the model to individual data, rather than group averages, we obtain a set of parameters for the performance and alertness models that are unique to each individual. We can then use other data collected from the individual, such as age, sex, habitual sleep time, morningness/eveningness preference, to determine correlations between model parameters and individual characteristics.

Specific Aim 4 (Work with NASA and NSBRI personnel to revise features of our current software to meet their specifications for administratively scheduling sleep, wake, and countermeasure design to minimize fatigue and performance issues): We have had discussions with NASA and NSBRI personnel to revise features of our current software to meet their specifications for administratively scheduling sleep, wake, and countermeasure design to minimize fatigue and performance issues, as well as incorporating the models into other modeling work performed by NASA. Dr. Barger used the software for NASA supported studies of sleep in ISS and Shuttle crew. We also developed a novel scheduling algorithm that automatically designs optimal light countermeasures for user-defined schedules The scheduling framework is applicable to other work schedules including shift-work and transmeridian travel.

Bibliography Type: Description: (Last Updated: 02/16/2021) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Phillips AJ, Breslow ER, Huang JM, St Hilaire MA, Klerman EB. "Adding circadian phase shifting effects of exogenous melatonin to a mathematical model of plasma melatonin." 26th Annual Meeting of the Associated Professional Sleep Societies, Boston, MA, June 9-13, 2012.

Sleep. 2012;35 Suppl:A70. http://www.journalsleep.org/Resources/Documents/2012abstractsupplement.pdf , Jun-2012

Abstracts for Journals and Proceedings Phillips AJ, Greenside P, Mistlberger R, Klerman EB. "A two oscillator model of food anticipatory activity." 13th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Destin, FL, May 19-23, 2012.

Program and Abstracts. 13th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Destin, FL, May 19-23, 2012. Abstract P132, p. 185. http://www.conferences.uiuc.edu/SRBR/FINAL%20SRBR%202012%20Program%20and%20Abstracts.pdf , May-2012

Abstracts for Journals and Proceedings Phillips AJ, Klerman EB. "The effects of chronic sleep restriction on sleep and performance in a physiologically based model of sleep." 26th Annual Meeting of the Associated Professional Sleep Societies, Boston, MA, June 9-13, 2012.

Sleep. 2012;35 Suppl:A117-8. http://www.journalsleep.org/Resources/Documents/2012abstractsupplement.pdf , Jun-2012

Abstracts for Journals and Proceedings Phillips AJ, Robinson P, Klerman EB. "Mathematical modeling reveals arousal state feedback as a potential physiological generator of the ultradian REM/NREM sleep cycle." 13th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Destin, FL, May 19-23, 2012.

Program and Abstracts. 13th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Destin, FL, May 19-23, 2012. Abstract S24, p. 62. http://www.conferences.uiuc.edu/SRBR/FINAL%20SRBR%202012%20Program%20and%20Abstracts.pdf , May-2012

Abstracts for Journals and Proceedings Phillips AJK, Chen PY, Robinson PA, Czeisler CA, Klerman EB. "Using Physiologically-based Modeling to Determine the Mechanisms Underlying Complex Sleep-Wake Dynamics." SIAM Conference on Life Sciences, Pittsburgh PA, July 12-15, 2010.

SIAM Conference on Life Sciences, Pittsburgh PA, July 12-15, 2010. LS10 abstract publication, p. 176. http://www.siam.org/meetings/ls10/LS10_abstracts.pdf , Jul-2010

Abstracts for Journals and Proceedings Phillips AJK, Klerman EB, Bianchi MT. "Noise induced transitions reproduce realistic sleep/wake architecture in a mathematical model of human sleep." 25th Annual Meeting of the Associated Professional Sleep Societies, LLC 2011, Minneapolis, MN, June 11-15, 2011.

Sleep 2011;34 Suppl:A36. http://www.journalsleep.org/Resources/Documents/2011abstractsupplement.pdf , Jun-2011

Abstracts for Journals and Proceedings Phillips AJK, Robinson PA, Klerman EB. "Ultradian dynamics in a potential formulation of human sleep." SIAM Conference on Dynamical Systems, Snowbird UT, May 22-26, 2011.

SIAM Conference on Dynamical Systems, Snowbird UT, May 22-26, 2011. Abstract publication DS11, p. 181. http://www.siam.org/meetings/ds11/DS11_abstracts.pdf , May-2011

Abstracts for Journals and Proceedings Wang W, Klerman EB. "Using the random-effects zero-inflated Poisson model to analyze activity count data." 26th Annual Meeting of the Associated Professional Sleep Societies, Boston, MA, June 9-13, 2012.

Sleep. 2012;35 Suppl:A133. http://www.journalsleep.org/Resources/Documents/2012abstractsupplement.pdf , Jun-2012

Abstracts for Journals and Proceedings Phillips AJK, Klerman EB. "Physiologically-based modeling of sleep-wake schedules and the effects of pharmaceuticals." 2010 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 3-5, 2010.

2010 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 3-5, 2010. http://www.dsls.usra.edu/meetings/hrp2010/pdf/Postdocs/1137Phillips.pdf , Feb-2010

Abstracts for Journals and Proceedings Cain SW, Vlassac I, Gooley JJ, Rahman S, Van Reen E, Rueger M, St Hilaire M, Klerman EB, Czeisler C, Lockley SW. "Sex differences in seasonal timing of the circadian clock in humans." 13th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Destin, FL, May 19-23, 2012.

Program and Abstracts. 13th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Destin, FL, May 19-23, 2012. Abstract S66, p. 90. http://www.conferences.uiuc.edu/SRBR/FINAL%20SRBR%202012%20Program%20and%20Abstracts.pdf , May-2012

Abstracts for Journals and Proceedings Dean DA, Beckett SA, Klerman EB, Landrigan CP. "Simulations of rotation schedules for teams of resident-physicians can identify potential areas of low performance and guide residency schedule design." 25th Annual Meeting of the Associated Professional Sleep Societies, LLC 2011, Minneapolis, MN, June 11-15, 2011.

Sleep 2011;34 Suppl:A342-3. http://www.journalsleep.org/Resources/Documents/2011abstractsupplement.pdf , Jun-2011

Abstracts for Journals and Proceedings Dean DA, St Hilaire MA, Phillips AJK, Sriram K, Wang W, Klerman EB. "Designing individual countermeasures to reduce sleep disruption and improve performance and alertness in space." NASA Ames/Moffett Field/05-201, May 2011.

NASA Ames/Moffett Field/05-201 abstract publication. May 2011. , May-2011

Abstracts for Journals and Proceedings Dean DA, Nguyen DP, Adler GK, Klerman EB, Brown EN. "Extracting Quantitative and Qualitative Features from Frequently Sampled Cortisol Time Series with Hierarchically Adaptive Hormone Analysis." 10th Annual New England Science Symposium, Boston, MA, April 1, 2011.

10th Annual New England Science Symposium, Boston, MA, April 1, 2011. , Apr-2011

Abstracts for Journals and Proceedings Dean DA, Nguyen DP, Schmid CH, Adler GK, Klerman EB, Brown EN. "A Sequential Dynamical System Representation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis." Conference for African American Researchers in the Mathematical Sciences, Baltimore, MD, June 15-18, 2010.

Conference for African American Researchers in the Mathematical Sciences, Baltimore, MD, June 15-18, 2010. , Jun-2010

Abstracts for Journals and Proceedings Dean DA. "From Mathematical Models to Hypothesis Generation: Examples from Experiment and Schedule Design." 2010 Sleep Research Network Annual Conference, Arlington, VA, October 13, 2010.

2010 Sleep Research Network Annual Conference, Arlington, VA, October 13, 2010. , Oct-2010

Abstracts for Journals and Proceedings Dean DA. "Mathematics You Won't Sleep On." NAM Granville-Brown-Haynes Session of Presentations by Recent Doctoral Recipients in the Mathematical Sciences. 2012 Joint Mathematics Meetings, Boston, MA, January 4-7, 2012.

NAM Granville-Brown-Haynes Session of Presentations by Recent Doctoral Recipients in the Mathematical Sciences. 2012 Joint Mathematics Meetings, Boston, MA, January 4-7, 2012. http://jointmathematicsmeetings.org/amsmtgs/2138_abstracts/1077-92-2576.pdf , Jan-2012

Abstracts for Journals and Proceedings Dean DA. "Sleep in Action: My Computational Methods Unravel Dynamic Effects." Conference for African American Researchers in the Mathematical Sciences, Princeton, NJ, June 27-30, 2012.

Conference for African American Researchers in the Mathematical Sciences, Princeton, NJ, June 27-30, 2012. , Jun-2012

Abstracts for Journals and Proceedings Klerman EB, Dijk DJ. "Assessment of the ability to recover sleep after sleep deprivation in a sleep satiation protocol" 26th Annual Meeting of the Associated Professional Sleep Societies, Boston, MA, June 9-13, 2012.

Sleep. 2012;35 Suppl:A60. http://www.journalsleep.org/Resources/Documents/2012abstractsupplement.pdf , Jun-2012

Abstracts for Journals and Proceedings Srinivasan P, Dean DA, Silva EJ, Wang W, Beckett SA, Duffy JF, Klerman EB. "Comparison of Ambulatory Actigraphy and Sleep/wake Diary Input to a Circadian-Light Model For Predicting Circadian Phase." 25th Annual Meeting of the Associated Professional Sleep Societies, LLC 2011, Minneapolis, MN, June 11-15, 2011.

Sleep 2011;34 Suppl:A330. http://www.journalsleep.org/Resources/Documents/2011abstractsupplement.pdf , Jun-2011

Abstracts for Journals and Proceedings Srinivasan P, Dean DA, Horowitz T, Klerman EB. "Actigraphy as input to a circadian light model predicts relative impact of bright light and sleep schedule on circadian phase during a simulated shift-work protocol." 25th Annual Meeting of the Associated Professional Sleep Societies, LLC 2011, Minneapolis, MN, June 11-15, 2011.

Sleep 2011;34 Suppl:A330. http://www.journalsleep.org/Resources/Documents/2011abstractsupplement.pdf , Jun-2011

Abstracts for Journals and Proceedings Sazuka N, Wang W, Wyatt JK, Czeisler CA, Klerman EB. "Differential effects of two alertness promoting agents on sleep quantified using transition analysis." 13th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Destin, FL, May 19-23, 2012.

Program and Abstracts. 13th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Destin, FL, May 19-23, 2012. Abstract P135, p. 187. http://www.conferences.uiuc.edu/SRBR/FINAL%20SRBR%202012%20Program%20and%20Abstracts.pdf , May-2012

Abstracts for Journals and Proceedings Sazuka N, Wang W, Wyatt JK, Gronfier C, Klerman EB. "Sleep state continuity varies by time in sleep episode." 21st Congress of the European Sleep Research Society, Paris, France, September 4-8, 2012.

21st Congress of the European Sleep Research Society, Paris, France, September 4-8, 2012. Program and abstracts, p. 604. , Sep-2012

Abstracts for Journals and Proceedings St Hilaire MA, Kim H, Klerman EB. "Incorporating the Dose-Dependent Direct Alerting Effect of Light into a Mathematical Model of Sleep, Circadian Rhythms, Performance and Alertness." 26th Annual Meeting of the Associated Professional Sleep Societies, Boston, MA, June 9-13, 2012.

Sleep. 2012;35 Suppl:A64. http://www.journalsleep.org/Resources/Documents/2012abstractsupplement.pdf , Jun-2012

Abstracts for Journals and Proceedings St Hilaire MA, Klerman EB. "Age-related Differences in the Effect of Inter-stimulus Interval and Time on Task on PVT Response Times." 26th Annual Meeting of the Associated Professional Sleep Societies, Boston, MA, June 9-13, 2012.

Sleep. 2012;35 Suppl:A18. http://www.journalsleep.org/Resources/Documents/2012abstractsupplement.pdf , Jun-2012

Abstracts for Journals and Proceedings St Hilaire MA, Rahman SA, Kronauer RE, Lockley SW, Klerman EB. "What short duration light pulses can tell us about human circadian photoreception: results from modeling and experiments." 23rd Annual Meeting Society of Light Treatment and Biological Rhythms, Montreal, Quebec, Canada, July 10-13, 2011.

23rd Annual Meeting Society of Light Treatment and Biological Rhythms, Montreal, Quebec, Canada, July 10-13, 2011. Program and Abstracts, vol. 23, p. 67. , Jul-2011

Articles in Peer-reviewed Journals Bermudez EB, Klerman EB, Czeisler CA, Cohen DA, Wyatt JK, Phillips AJ. "Prediction of vigilant attention and cognitive performance using self-reported alertness, circadian phase, hours since awakening, and accumulated sleep loss." PLoS One. 2016 Mar 28;11(3):e0151770. eCollection 2016. http://dx.doi.org/10.1371/journal.pone.0151770 ; PubMed PMID: 27019198; PubMed Central PMCID: PMC4809494 , Mar-2016
Articles in Peer-reviewed Journals Faghih RT, Dahleh MA, Adler GK, Klerman EB, Brown EN. "Quantifying pituitary-adrenal dynamics and deconvolution of concurrent cortisol and adrenocorticotropic hormone data by compressed sensing." IEEE Trans Biomed Eng. 2015 Oct;62(10):2379-88. Epub 2015 Apr 29. http://dx.doi.org/10.1109/TBME.2015.2427745 ; PubMed PMID: 25935025; PubMed Central PMCID: PMC4579049 , Oct-2015
Articles in Peer-reviewed Journals Dean DA 2nd, Adler GK, Nguyen DP, Klerman EB. "Biological time series analysis using a context free language: applicability to pulsatile hormone data." PLoS One. 2014 Sep 3;9(9):e104087. eCollection 2014. http://dx.doi.org/10.1371/journal.pone.0104087 ; PubMed PMID: 25184442; PubMed Central PMCID: PMC4153563 , Sep-2014
Articles in Peer-reviewed Journals Bianchi MT, Wang W, Klerman EB. "Sleep misperception in healthy adults: implications for insomnia diagnosis." J Clin Sleep Med. 2012 Oct 15;8(5):547-54. http://dx.doi.org/10.5664/jcsm.2154 ; PubMed PMID: 23066367 , Oct-2012
Articles in Peer-reviewed Journals Klerman EB, Wang W, Duffy JF, Dijk DJ, Czeisler CA, Kronauer RE. "Survival analysis indicates that age-related decline in sleep continuity occurs exclusively during NREM sleep." Neurobiol Aging. 2013 Jan;34(1):309-18. Epub 2012 Jun 23. http://dx.doi.org/10.1016/j.neurobiolaging.2012.05.018 ; PubMed PMID: 22727943 , Jan-2013
Articles in Peer-reviewed Journals Klerman H, St Hilaire MA, Kronauer RE, Gooley JJ, Gronfier C, Hull JT, Lockley SW, Santhi N, Wang W, Klerman EB. "Analysis method and experimental conditions affect computed circadian phase from melatonin data." PLoS One. 2012;7(4):e33836. Epub 2012 Apr 12. http://dx.doi.org/10.1371/journal.pone.0033836 ; PubMed PMID: 22511928 , Apr-2012
Articles in Peer-reviewed Journals Phillips AJK, Czeisler CA, Klerman EB. "Revisiting spontaneous internal desynchrony using a quantitative model of sleep physiology." J Biol Rhythms. 2011 Oct;26(5):441-53. http://dx.doi.org/10.1177/0748730411414163 ; PubMed PMID: 21921298 , Oct-2011
Articles in Peer-reviewed Journals St. Hilaire MA, Sullivan JP, Anderson C, Cohen DA, Barger LK, Lockley SW, Klerman EB. "Classifying performance impairment in response to sleep loss using pattern recognition algorithms on single session testing." Accid Anal Prev. 2013 Jan;50:992-1002. Epub 2012 Sep 5. http://dx.doi.org/10.1016/j.aap.2012.08.003 ; PubMed PMID: 22959616 , Jan-2013
Awards Dean DA. "Carl Storm Underrepresented Minority Fellowship, Gordon Research Conference, January 2010." Jan-2010
Awards Dean DA. "Gordon Research Conference in Pineal Cell Biology Trainee Travel Award, January 2010." Jan-2010
Awards Dean DA. "Ruth and William Silen, M.D. Award, third place in oral presentation category, New England Science Symposium, Boston, MA, January 2011." Jan-2011
Awards Dean DA. "Sleep Research Network Minority Trainee Travel Award, October 2010, for paper 'From Mathematical Models to Hypothesis Generation: Examples from Experiment and Schedule Design'. " Oct-2010
Awards Dean DA. "Travel Sponsorship, Conference of African American Researchers in the Mathematical Sciences, January 2010." Jan-2010
Awards Dean DA. "Travel Sponsorship, Mathematical Neuroendocrinology Workshop sponsored by the Mathematical Biosciences Institute, January 2010." Jan-2010
Awards Phillips AJK. "Abstract Honorable Mention Award, Sleep Research Society, June 2012." Jun-2012
Awards Phillips AJK. "Research Merit Award, Society for Research in Biological Rhythms, May 2012." May-2012
Awards Phillips AJK. "Richard E Kronauer Award for Excellence in Biomathematical Modeling, May 2010." May-2010
Awards Redline SA, Dean DA. "National Institute of Health Research Supplement to Promote Diversity in Health-Related Research for Individuals in Postdoctoral Training (3R01HL098433-02S1), January 2012." Jan-2012
Awards St Hilaire M. "2011 Sleep Research Society Abstract Excellence award, June 2011." Jun-2011
Awards St Hilaire M. "2012 Sleep Research Society Honorable Mention Abstract award, June 2012." Jun-2012
Awards St Hilaire M. "Honorable Mention, 2011 Ford Foundation Dissertation Fellowship, April 2011." Apr-2011
Awards St Hilaire M. "Scientific Merit Trainee Travel Award, Sleep Research Society, May 2011." May-2011
Awards Dean DA. "National Institute of Health Ruth L. Kirschstein National Research Service Award (NRSA) Predoctoral Fellowship Award to Promote Diversity in Health Related Research (NIH-F31), Boston, MA, January 2011." Jan-2011
Dissertations and Theses Dean DA. "Integrating Formal Language Theory with Mathematical Modeling to Solve Computational Issues in Sleep and Circadian Applications." University of Massachusetts, Intercampus Biomedical Engineering and Biotechnology Program, June 2011. , Jun-2011
Papers from Meeting Proceedings Beckett SA, Dean DA, Klerman EB, Landrigan CP. "Performance simulations of current and proposed schedules highlight the need for reform." 20th International Symposium on Shiftwork and Working Time: Biological mechanisms and risk management in the 24h society, Stockholm, Sweden, June 28-July 1, 2011.

20th International Symposium on Shiftwork and Working Time: Biological mechanisms and risk management in the 24h society, Stockholm, Sweden, June 28-July 1, 2011. , Jun-2011

Project Title:  Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness in Space Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 06/01/2008  
End Date: 09/30/2012  
Task Last Updated: 06/08/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Klerman, Elizabeth B. M.D., Ph.D. / Brigham and Women's Hospital/Harvard Medical Center 
Address:  Department of Medicine 
Division of Sleep Medicine 
Boston , MA 02115-5804 
Email: ebklerman@hms.harvard.edu 
Phone: 617-732-8145  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham and Women's Hospital/Harvard Medical Center 
Joint Agency:  
Comments:  
Project Information: Grant/Contract No. NCC 9-58-HFP01603 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01603 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) BHP:Behavioral Health & Performance (archival in 2017)
Human Research Program Risks: (1) Sleep:Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload (IRP Rev F)
Human Research Program Gaps: (1) Sleep Gap 04:We need to identify indicators of individual vulnerabilities and resiliencies to sleep loss and circadian rhythm disruption, to aid with individualized countermeasure regimens, for autonomous, long duration and/or distance exploration missions (IRP Rev E)
(2) Sleep Gap 08:We need to develop individualized scheduling tools that predict the effects of sleep-wake cycles, light and other countermeasures on performance, and can be used to identify optimal (and vulnerable) performance periods during spaceflight (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date change to 9/30/2012 (from 5/31/2012) per NSBRI (Ed., 1/24/2012)

Task Description: Objective neurobehavioral performance, subjective alertness, and sleep are critically important to astronaut and ground-based crew health and to ensure the success of space missions. Neurobehavioral performance and alertness are affected by changes in circadian rhythms, homeostatic sleep/wake regulation and sleep inertia, and the interactions of these processes. During space missions, circadian rhythms and sleep are disrupted, both for astronauts and ground-based crew. Problems with sleep, circadian rhythms and performance have been reported in astronauts, and NASA data indicate that sleeping pills are among the most commonly used drugs in space. Therefore, it is imperative that work and sleep/wake schedules, including the timing of countermeasures such as light, are designed to optimize individual performance, alertness, and sleep quality relative to operational requirements. Our approach to designing countermeasures is to develop new scheduling techniques and software that use mathematical models to describe the underlying physiology of internal timing, performance and sleep.

We have developed and validated two linked mathematical models: one of the human circadian pacemaker that includes the influence of light and of non-photic processes, and one of performance and alertness that includes the key processes of circadian rhythms, sleep/wake homeostasis and sleep inertia. Together, these models are able to predict the effects of sleep/wake, sleep inertia and circadian phase on performance and alertness. Each performance or alertness measure has a separate equation, reflecting the underlying physiological processes in the effect of sleep/wake on performance and alertness. CPSS, the software implementing this model, has been used by NASA and consultants when designing light countermeasures for astronaut pre-launch schedules as well as for designing in-flight schedules. To further improve this mathematical model and this method for optimal design of countermeasures, our s modeling work will focus on individual, rather than group, predictions and use novel non-linear mathematical and statistical methods. These projects address NASA's objectives to improve the design of individual countermeasures to reduce sleep disruption and improve performance and alertness in space and on Earth. Our current progress includes:

We developed a novel scheduling algorithm called Shifter that automatically designs optimal light countermeasures for user-defined NASA-related schedules. Light interventions have been demonstrated to minimize fatigue, improve performance, and improve sleep in experimental and field studies. Shifter allows individuals who are not circadian experts to design schedules and light interventions within minutes. Previous design of light interventions, such as for the 24.65-hr Mars Day experimental protocol (NASA and NSBRI supported, Dr. Czeisler, PI), took approximately two weeks. The scheduling framework can be applied to non-NASA-related work schedules including shift-work and transmeridian travel. We are currently applying our methods to the design of schedules for medical residents, so as to provide schedules that predict optimal performance at critical times and meet new national guidelines for restricted physician hours. Abstracts have been accepted on this scheduling work and will be presented at national and international meetings.

We are developing new methods to refine the scheduling algorithm for predicting individual differences in circadian phase and performance. We are individualizing predictions based on easily collected trait information (e.g., age, chronotype), and developing a statistical framework for making individual predictions. Experimental evidence demonstrates changes in physiology are well correlated with age and specialized questionnaire results (e.g., habitual sleep time is highly correlated with circadian phase). The work of Dr. Phillips (NSBRI post-doctoral fellow) has quantified mechanisms underlying individual differences in physiologically-determined sleep timing and self-reported (subjective) chronotype (e.g., "owl" or "lark").

Using synergistic support from a NIH "Grand Opportunities" grant to Dr. Klerman, we are developing and populating a database with studies from the BWH Division of Sleep Medicine. The database has enabled a larger data set for our modeling work and will facilitate the building of individual models using demographic data as described above.

To assess the ability of individuals to conform to scheduled work hours, Dr. Phillips is integrating the circadian and performance model with a model of the physiological mechanisms which control sleep-wake transitions. This combined model dynamically predicts wake/sleep state across a simulated protocol, allowing predictions of sleep efficiency, and likelihood of falling asleep during scheduled wake periods. This model has been validated using BWH datasets; several abstracts have been published on this work. Since the model is physiologically based, it is being extended to incorporate pharmaceutical effects, including simulating the effects of melatonin and caffeine at different times and dosages.

We are targeting the use of actigraphy, which is an inexpensive and less intrusive alternative to polysomnography, to determine sleep/wake state and then use the mode to predict circadian phase and performance without other inputs. Several abstracts have been published on this work.

Our NSBRI-funded work is broadly applicable to diverse work environments, ranging from NASA missions to industries such as aviation, transportation, and the military. We are also working with the NSBRI Industry Forum to explore ways to facilitate use of our work in these diverse environments. We continue to work with NASA and NSBRI personnel to meet their requests regarding use of the models and software.

Research Impact/Earth Benefits: The development of (1) mathematical models of circadian rhythms, sleep, alertness and performance, and (2) software based on these models that aid in schedule design, can improve performance and alertness and thereby effectiveness and public safety for people who work at night, on rotating schedules, on non-24-hr schedules or on extended duty schedules (e.g., pilots, train and truck drivers, shift workers, health care workers, public safety officers). Attempting to sleep at adverse circadian phases is difficult, resulting in poor sleep efficiency. Similarly, attempting to work at adverse circadian phases and/or after a long time awake, results in poor worker performance and productivity, and increased errors. For example, the accidents at the Chernobyl and Three Mile Island nuclear reactors and the Exxon Valdez grounding were all partially attributed to employees working at adverse circadian phases and the recent FAA reports of air traffic controllers sleeping while scheduled to work at night are related to the work schedule (5 shifts in 4 days) and night-time work. The mathematical models and the available software implementing these models can be used to simulate and quantitatively evaluate different scenarios of sleep/wake schedules and light exposure to predict the resulting circadian phase and amplitude, subjective alertness and performance in an individual. Our software has been requested by members of academia, government and industry, including airline, safety, medical, and military applications. Its use could help produce improved work schedules for both astronauts and ground-crew.

The ease of use of the modeling has been improved by the recent incorporation of actigraphy as input of actual sleep/wake time to the mathematical model. The use of actigraphy as a tool to record sleep has improved the confidence levels on the daily assessment of sleep when compared to the use of sleep logs, as well as reduced the user requirements for maintaining daily logs. The interface between actigraphy and the Circadian Performance Simulation Software (CPSS) enables faster and possibly more accurate predictions of circadian phase and performance parameters. The Shifter software now includes optimal countermeasure design, so that countermeasures can be planned for times of predicted poor performance and alertness. The schedule/countermeasure design program allows users to interactively design schedules and implement mathematically optimal light countermeasures (including intensity, duration and placement) to minimize worker fatigue. This scheduling software will be valuable to those who work at night, on rotating schedules, on non-24-hr schedules or extended duty schedules. The software allows individuals to design countermeasures for their assigned work schedules so that their sleep and wake rhythms will be adjusted for optimal performance at desired times, both with respect to scheduled work events and with their circadian phase. Improving sleep duration and quality can also decrease the risk of accidents and errors, as well as decrease the long-term risks of cardiovascular, metabolic, immune and psychological pathologies.

The mathematical modeling has been used for basic scientific research. Inclusion of mathematical models in the planning process to optimize measures to be studied in experimental protocols enables more efficient use of research resources and directs new research. If the modeling of existing experimental data is found to be unsatisfactory, then model assumptions may need to be revised; this revision may include identification of a new physiological process not previously described.

The mathematical modeling efforts and software have also been used in educational programs and in the popular press to teach students, teachers and health care professionals about circadian rhythms and sleep, work schedules and their effects on alertness and performance.

Task Progress & Bibliography Information FY2011 
Task Progress: Specific Aim 1 (predicting sleep-wake within scheduled sleep). We have integrated the existing circadian/performance model with a physiological model of sleep/wake transitions. This integrated model can predict whether individuals are able to conform to enforced work schedules, including estimated likelihood of insomnia during scheduled sleep periods or difficulty remaining awake during working hours. In the current year, we have been validating this integrated model against human data from a variety of sleep/wake schedule protocols. The model has now been used to relate inter-individual differences in sleep timing (e.g., self-reported chronotype) to differences in underlying physiology and provides a novel method for improving parameter estimates on an individual basis.

Specific Aim 2 (actigraphy) We have integrated the output from actigraphy data with the input required to run our Circadian Performance Simulation Software (CPSS), which utilizes our mathematical model of the human circadian pacemaker, performance and alertness, that includes the key processes of circadian rhythms, sleep/wake homeostasis and sleep inertia as well as the effects of light on circadian rhythms. Pre-processing tools have been developed to generate the sleep/wake schedule and light levels from raw or processed actigraphy data. The sleep/wake and lighting schedule thus generated may be used as input to CPSS. In the current year, we have been testing the ability of outpatient actigraphy as input to CPSS to predict inpatient circadian phase for individuals with habitual sleep/wake schedules (sleep at night and wake during the day).

Specific Aim 3 (Statistical modeling of individual circadian, sleep, performance and alertness parameters): We have concentrated on statistical modeling of individual circadian parameters of our circadian, performance and alertness models.to obtain a set of parameters for the performance and alertness models unique to each individual. We are using other data collected from the individual, such as age, gender, habitual sleep time, morningness/eveningness preference, etc. to determine correlations between model parameters and individual characteristics. In the current year of this project, we have been working on a new BWH Division of Sleep Medicine Database, supported by both this NSBRI grant and a NIH grant to Dr. Klerman to facilitate the development of individualized models.

Specific Aim 4 (Work with NASA and NSBRI personnel to revise features of our current software to meet their specifications for administratively scheduling sleep, wake and countermeasure design to minimize fatigue and performance issues.): We have had discussions with NASA and NSBRI personnel to revise features of our current software to meet their specifications for administratively scheduling sleep, wake and countermeasure design to minimize fatigue and performance issues, as well as incorporating the models into other modeling work performed by NASA.

Bibliography Type: Description: (Last Updated: 02/16/2021) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Phillips A, Czeisler C, Klerman E. "Investigating the causes of spontaneous internal desynchrony using a physiologically based sleep model." 12th Biennial Meeting, Society for Research in Biological Rhythms (SRBR), Destin, FL, May 22-26, 2010.

Program and Abstracts. 12th Biennial Meeting, Society for Research in Biological Rhythms (SRBR), Destin, FL, May 22-26, 2010. Abstract P94, p. 126. , May-2010

Abstracts for Journals and Proceedings Phillips AJ, Czeisler CA, Klerman EB. "Predicting sleep/wake schedule compliance using a physiologically based model of sleep." SLEEP 2010. 24th Annual Meeting of the Associated Professional Sleep Societies, LLC, San Antonio, TX, June 5-9, 2010.

Sleep 2010;33 Suppl:A71-2. http://www.journalsleep.org/PDF/AbstractBook2010.pdf , May-2010

Abstracts for Journals and Proceedings Phillips AJ, Klerman EB. "Understanding internal desynchrony and the physiological effects of self-selected schedules using a quantitative model of sleep physiology." SLEEP 2010. 24th Annual Meeting of the Associated Professional Sleep Societies, LLC, San Antonio, TX, June 5-9, 2010.

Sleep 2010;33 Suppl:A60. http://www.journalsleep.org/PDF/AbstractBook2010.pdf , May-2010

Abstracts for Journals and Proceedings Phillips AJK, Breslow E, Huang J, St Hilaire MA, Klerman EB. "Adding melatonin countermeasures to a model of human sleep/wake and circadian rhythms." 18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011.

18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011. , Apr-2011

Abstracts for Journals and Proceedings Phillips AJK, Fulcher BD, Robinson PA, Klerman EB. "Diurnal and nocturnal preference in a physiologically based model of mammalian sleep." 12th Biennial Meeting, Society for Research in Biological Rhythms (SRBR), Destin, FL, May 22-26, 2010.

Program and Abstracts. 12th Biennial Meeting, Society for Research in Biological Rhythms (SRBR), Destin, FL, May 22-26, 2010. Abstract P59, p. 106. , May-2010

Abstracts for Journals and Proceedings Srinivasan P, Dean DA 2nd, Silva E, Wang W, Beckett SA, Duffy JF, Klerman EB. "Ambulatory Actigraphy Input to a Circadian-Light Model Can Predict Circadian Phase." 18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011.

18th IAA Humans in Space Symposium, Houston, TX, April 11-15, 2011. , Apr-2011

Abstracts for Journals and Proceedings St Hilaire MA, Klerman EB. "Pattern recognition algorithms to classify performance decrement using both subjective and objective measures." SLEEP 2010. 24th Annual Meeting of the Associated Professional Sleep Societies, LLC, San Antonio, TX, June 5-9, 2010.

Sleep 2010;33 Suppl:A96. http://www.journalsleep.org/PDF/AbstractBook2010.pdf , May-2010

Abstracts for Journals and Proceedings St Hilaire MA, Rahman SA, Kronauer RE, Lockley SW, Klerman EB. "The effect of a single continuous two minute bright light pulse on the human circadian pacemaker." 25th Annual Meeting of the Associated Professional Sleep Societies, LLC 2011, Minneapolis, MN, June 11-15, 2011.

Sleep 2011;34 Suppl:A56-7. http://www.journalsleep.org/Resources/Documents/2011abstractsupplement.pdf , May-2011

Abstracts for Journals and Proceedings St Hilaire MA, Wang W, Klerman EB. "Inter-individual variability in the parameters of a mathematical model of neurobehavioral performance and alertness: relationships with subject characteristics." SLEEP 2010. 24th Annual Meeting of the Associated Professional Sleep Societies, LLC, San Antonio, TX, June 5-9, 2010.

Sleep 2010;33 Suppl:A94. http://www.journalsleep.org/PDF/AbstractBook2010.pdf , May-2010

Abstracts for Journals and Proceedings Dean DA, Beckett SA, Klerman EB, Landrigan CP. "Simulations of rotation schedules for teams of resident-physicians can identify potential areas of low performance and guide residency schedule design." 25th Annual Meeting of the Associated Professional Sleep Societies, LLC 2011, Minneapolis, MN, June 11-15, 2011.

Sleep 2011;34 Suppl:A342-3. http://www.journalsleep.org/Resources/Documents/2011abstractsupplement.pdf , May-2011

Articles in Peer-reviewed Journals St Hilaire MA, Sullivan JP, Anderson C, Cohen DA, Barger LK, Lockley SW, Klerman EB. "Classifying performance impairment in response to sleep loss using pattern recognition algorithms." Sleep (revision requested), status as of April 2011. , Apr-2011
Awards Klerman E. "Elected to Sleep Research Society Board, April 2011." Apr-2011
Awards Klerman E. "Member, Association for Patient Oriented Research (APOR) Board, April 2011." Apr-2011
Awards Klerman E. "Nomination for 2010-2011 Harvard Medical School Excellence in Mentoring Award, October 2010." Oct-2010
Papers from Meeting Proceedings Beckett SA, Dean DAII, Klerman EB, Landrigan CP. "Performance simulations of current and proposed schedules highlight the need for reform." 20th International Symposium on Shiftwork and Working Time-- Biological mechanisms and risk management in the 24h society, Stockholm, Sweden, June 28-July 1, 2011.

20th International Symposium on Shiftwork and Working Time-- Biological mechanisms and risk management in the 24h society, Stockholm, Sweden, June 28-July 1, 2011. , Jul-2011

Papers from Meeting Proceedings Citi L, Klerman EB, Brown EN, Barbieri R. "Point Process Heart Rate Variability Assessment during Sleep Deprivation." Computing in Cardiology 2010, Belfast, Ireland, September 26-29, 2010.

Computing in Cardiology. 2010;37:721-4. http://www.cinc.org/archives/2010/pdf/0721.pdf , Sep-2010

Papers from Meeting Proceedings Mankowski P, Mueller R, Srinivasan P, Wang W, Klerman EB. "A framework for the integration and management of complex longitudinal multi-source datasets from outpatient and inpatient physiological monitoring studies." Great Lakes Bioinformatics (GLBIO) Conference 2011, Athens, Ohio, May 2-4, 2011.

Great Lakes Bioinformatics (GLBIO) Conference 2011, Athens, Ohio, May 2-4, 2011. https://www.iscb.org/cms_addon/conferences/glbio2011/track/oral.php#OP41 , May-2011

Project Title:  Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness in Space Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 05/21/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Klerman, Elizabeth B. M.D., Ph.D. / Brigham and Women's Hospital/Harvard Medical Center 
Address:  Department of Medicine 
Division of Sleep Medicine 
Boston , MA 02115-5804 
Email: ebklerman@hms.harvard.edu 
Phone: 617-732-8145  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham and Women's Hospital/Harvard Medical Center 
Joint Agency:  
Comments:  
Project Information: Grant/Contract No. NCC 9-58-HFP01603 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01603 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) BHP:Behavioral Health & Performance (archival in 2017)
Human Research Program Risks: (1) Sleep:Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload (IRP Rev F)
Human Research Program Gaps: (1) Sleep Gap 04:We need to identify indicators of individual vulnerabilities and resiliencies to sleep loss and circadian rhythm disruption, to aid with individualized countermeasure regimens, for autonomous, long duration and/or distance exploration missions (IRP Rev E)
(2) Sleep Gap 08:We need to develop individualized scheduling tools that predict the effects of sleep-wake cycles, light and other countermeasures on performance, and can be used to identify optimal (and vulnerable) performance periods during spaceflight (IRP Rev E)
Task Description: Objective neurobehavioral performance, subjective alertness, and sleep are critically important to astronaut and ground-based crew health and to ensure the success of space missions. Neurobehavioral performance and alertness are affected by changes in circadian rhythms, homeostatic sleep/wake regulation and sleep inertia, and the interactions of these processes. During space missions, circadian rhythms and sleep are disrupted, both for those in space and for those on Earth. Problems with sleep, circadian rhythms and performance have been reported in astronauts, and NASA data indicate that sleeping pills are among the most commonly used drugs in space. Therefore, it is imperative that schedules and countermeasures are designed to optimize individual performance, alertness, and sleep quality relative to operational requirements. Our approach to designing countermeasures is to develop new scheduling techniques and software that use mathematical models to describe the underlying physiology of internal timing, performance and sleep.

We have developed and validated a mathematical model of the human circadian pacemaker that includes the key processes of circadian rhythms, sleep/wake homeostasis and sleep inertia, and is able to predict the effects of sleep/wake and circadian phase on performance and alertness. The software implementing this model has been used by NASA and consultants when designing light countermeasures for astronaut pre-launch schedules as well as for designing in-flight schedules. To further improve this mathematical model and this method for optimal design of countermeasures, our specific aims are to: (1) Replace the current assumption that an individual sleeps when scheduled to sleep, with probabilities of sleep and wake during those times; (2) Improve daily assessment of sleep and sleep disruption using actigraphy data; (3) Add statistical features including confidence limits to the predictions; (4) Update the software per astronaut and ground crew requests for specific features and reports. The basic mathematical work will focus on individual, rather than group, predictions and use novel non-linear mathematical and statistical measures. These projects address NASA's objectives to improve the design of individual countermeasures to reduce sleep disruption and improve performance and alertness in space and on Earth. Our current progress is as follows:

The major advance in the last year was the publication of a novel scheduling algorithm called Shifter in PLoS Computational Biology. The algorithm automatically designs optimal light countermeasures for user-defined NASA related schedules. These light interventions have been demonstrated to minimize fatigue, improve performance, and improve sleep in experimental and field studies. Developing Shifter required several mathematical and computational advances, including the development of a novel schedule representation and scheduling algorithm. Shifter for the first times allows individuals who are not circadian experts to design schedules and light interventions. Using Shifter, schedules are produced within a minute; previous design of light interventions, such as for the Mars Day protocol, took approximately two weeks with multiple iterations of CPSS and other software. The scheduling framework has also been designed to be applicable to work schedules including shift-work and transmeridian travel. To this end, we have begun applying our methods to the design of schedules for medical residents, so as to provide schedules that predict optimal performance while meeting new guidelines for restricted physician hours.

We are extending our current models and developing new methods to refine the scheduling algorithm for predicting individual differences in circadian phase and performance. To achieve this, we are individualizing predictions based on easily collected trait information (e.g., age, chronotype), and developing a statistical framework for building individual models. Experimental evidence demonstrates changes in physiology are well correlated with age and specialized questionnaire results (e.g., habitual sleep time is highly correlated with circadian phase). This is important because circadian phase correlates with intrinsic circadian period, which we have shown to be the most important input to generating accurate individualized predictions. Further work will involve identifying other demographics which can be used as proxies for physiological parameters.

The use of sleep aids during NASA missions is indicative of the difficulties astronauts face in sleeping during space flight. To assess the ability of individuals to conform to scheduled work hours, we are integrating the circadian and performance model with a model of the physiological mechanisms which control sleep-wake transitions. This combined model dynamically predicts wake/sleep state across a simulated protocol, allowing predictions of sleep efficiency, and likelihood of falling asleep during scheduled wake periods.

Integral to successfully using these methods in space is the ability to assess physiological state, and make individualized predictions. Since sleep is a core issue in space, we are targeting use of actigraphy, which is an inexpensive and less intrusive alternative to polysomnography. Our current work allows us to predict sleep state, circadian phase and performance directly from actigraphy.

Our plan is to use this information as input to our scheduling algorithm, resulting in individualized countermeasure predictions in real-time. The key benefit of these new methods is the ability to investigate different schedules, and to adaptively respond to changes that are unavoidable, such as launch rescheduling due to inclement weather. Our NSBRI-funded work is broadly applicable to diverse work environments, ranging from NASA missions to industries such as aviation, transportation, and the military.

Research Impact/Earth Benefits: The development of (1) mathematical models of circadian rhythms, sleep, alertness and performance, and (2) software based on these models that aid in schedule design, can improve performance and alertness and thereby effectiveness and public safety for people who work at night, on rotating schedules, on non-24-hr schedules or extended duty schedules (e.g., pilots, train and truck drivers, shift workers, health care workers, public safety officers). Attempting to sleep at adverse circadian phases is difficult, resulting in poor sleep efficiency. Similarly, attempting to work at adverse circadian phases and/or after a long time awake, results in poor worker performance and productivity, and increased errors. For example, the accidents at the Chernobyl and Three Mile Island nuclear reactors and the Exxon Valdez grounding were all partially attributed to employees working at adverse circadian phases. The mathematical models and the available software implementing these models can be used to simulate and quantitatively evaluate different scenarios of sleep/wake schedules and light exposure to predict the resulting circadian phase and amplitude, subjective alertness and performance. Our software has been requested by members of academia, government and industry, including airline, safety, medical, and military applications. Its use could help produce improved work schedules for both astronauts and ground-crew.

The recent incorporation of actigraphy as input to the mathematical model as a tool to record sleep has improved the confidence levels on the daily assessment of sleep when compared to the use of sleep logs. The interface between actigraphy and the Circadian Performance Simulation Software enables faster and possibly more accurate predictions of circadian phase and performance parameters. The software now also includes optimal countermeasure design, so that countermeasures can be planned for times of predicted poor performance and alertness. The schedule/countermeasure design program allows users to interactively design schedules and implement mathematically optimal light countermeasures (including intensity, duration and placement) to minimize worker fatigue. This scheduling software will be valuable to those who work at night, on rotating schedules, on non-24-hr schedules or extended duty schedules. The software allows individuals to design countermeasures for their assigned work schedules so that their sleep and wake rhythms will be adjusted for optimal performance at desired times, both with respect to scheduled work events and circadian phase. Improving sleep duration and quality can also decrease the risk of accidents and errors, as well as decrease the long-term risks of cardiovascular, metabolic, immune and psychological pathologies.

Mathematical modeling has been used for basic scientific research. Inclusion of mathematical models in the planning process to optimize measures to be studied in experimental protocols enables more efficient use of research resources and directs new research. If the modeling of existing experimental data is found to be unsatisfactory, then model assumptions may need to be revised. This revision may include identification of a new physiological process not previously described. As an example, an additional component (non-linear response to ocular light stimuli) was added to our mathematical model to describe data collected in our clinical research facilities, even before the anatomic and physiologic basis of this component was found. Later experiments validated this mathematical prediction. The proposed mathematical model, based on behavioral experimental findings, had uncovered previously unknown additional physiological processes at the cellular level.

The mathematical modeling efforts and software have also been used in educational programs and in the popular press to teach students and teachers about circadian rhythms and sleep and their effects on alertness and performance.

Task Progress & Bibliography Information FY2010 
Task Progress: Specific Aim 1 (predicting sleep-wake within scheduled sleep): We are integrating the existing circadian/performance model with a physiological model of sleep/wake transitions. This integrated model will predict whether individuals will be able to conform to enforced work schedules, including estimated likelihood of insomnia during scheduled sleep periods or difficulty remaining awake during working hours. In the current year of this project, we have been validating this integrated model against human data from a variety of sleep/wake schedule protocols.

Specific Aim 2 (actigraphy): We have integrated the output from actigraphy data with the input required to run our Circadian Performance Simulation Software (CPSS), which utilizes our mathematical model of the human circadian pacemaker, performance and alertness, that includes the key processes of circadian rhythms, sleep/wake homeostasis and sleep inertia as well as the effects of light on circadian rhythms. Pre-processing tools have been developed to generate the sleep/wake schedule and light levels from raw or processed actigraphy data. The sleep/wake and lighting schedule thus generated may be used as input to CPSS.

Specific Aim 3 (Statistical modeling of individual circadian, sleep, performance and alertness parameters): We have concentrated on statistical modeling of individual circadian parameters of our circadian, performance and alertness models. By fitting the model to individual, rather than grouped data, we obtain a set of parameters for the performance and alertness models unique to each individual. We can then use other data collected from the individual, such as age, gender, habitual sleep time, morningness/eveningness preference, etc. to determine correlations between model parameters and individual characteristics.

Specific Aim 4 (Work with NASA and NSBRI personnel to revise features of our current software to meet their specifications for administratively scheduling sleep, wake and countermeasure design to minimize fatigue and performance issues.): We have had discussions with NASA and NSBRI personnel to revise features of our current software to meet their specifications for administratively scheduling sleep, wake and countermeasure design to minimize fatigue and performance issues, as well as incorporating the models into other modeling work performed by NASA. As one example, we developed Shifter, a novel scheduling algorithm that automatically designs optimal light countermeasures for user defined schedules. Appropriate light interventions have been demonstrated to minimize fatigue, improve performance, and improve sleep in experimental and field studies. Developing Shifter required several mathematical and computational advances, including the development of a novel schedule representation and scheduling algorithm. The scheduling framework has also been designed to be applicable to work schedules including shift-work and transmeridian travel.

Bibliography Type: Description: (Last Updated: 02/16/2021) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings St Hilaire MA, Bullock D, Cohen D Czeisler CA, Klerman EB. "Within-session analysis of psychomotor vigilance reveals dependence of anticipations on inter-stimulus interval under act acute sleep deprivation and chronic sleep restriction." 23rd Annual Meeting of the Associated Professional Sleep Societies, LLC, Seattle, Wash., June 6-11, 2009.

23rd Annual Meeting of the Associated Professional Sleep Societies, LLC, Abstract Book, June 2009. , Jun-2009

Abstracts for Journals and Proceedings St Hilaire MA, Bullock D, Cohen D, Czeisler CA, Klerman EB. "Within-session analysis of psychomotor vigilance reveals changes in reaction time as time-on-task increases under acute sleep deprivation and chronic sleep restriction." 23rd Annual Meeting of the Associated Professional Sleep Societies, LLC, Seattle Wash., June 6-11, 2009.

23rd Annual Meeting of the Associated Professional Sleep Societies, LLC, Abstract Book, June 2009. , Jun-2009

Abstracts for Journals and Proceedings St Hilaire MA, Klerman EB. "Pattern recognition algorithms to classify performance on the psychomotor vigilance task." 2009 International Conference on Fatigue Management in Transportation Operations: A Framework for Progress, Boston, Mass., March 24-26, 2009.

2009 International Conference on Fatigue Management in Transportation Operations: A Framework for Progress, Abstract Book, March 2009. , Mar-2009

Abstracts for Journals and Proceedings Torgovitsky R, Wang W, DeGruttola V, Klerman E. "Nonparametric modeling of forced desynchrony data: Subject-specific evaluation of performance." 23rd Annual Meeting of the Associated Professional Sleep Societies, LLC, Seattle, Wash., June 6-11, 2009.

23rd Annual Meeting of the Associated Professional Sleep Societies, LLC, Abstract Book, June 2009. , Jun-2009

Abstracts for Journals and Proceedings Torgovitsky R, Wang W, DeGruttola V, Klerman EB. "Subject-specific evaluation of performance based on forced desynchrony data." 2009 International Conference on Fatigue Management in Transportation Operations: A Framework for Progress, Boston, Mass., March 24-26, 2009.

2009 International Conference on Fatigue Management in Transportation Operations: A Framework for Progress, Abstract Book, March 2009. , Mar-2009

Articles in Peer-reviewed Journals Cohen DA, Wang W, Wyatt JK, Kronauer RE, Dijk DJ, Czeisler CA, Klerman EB. "Uncovering residual effects of chronic sleep loss on human performance." Science Translational Medicine. 2010 Jan 13;2(14):14ra3. PubMed PMID: 20371466 , Jan-2010
Articles in Peer-reviewed Journals Dean DA 2nd, Forger DB, Klerman EB. "Taking the lag out of jet lag through model-based schedule design." PLoS Comput Biol. 2009 Jun;5(6):e1000418. PubMed PMID: 19543382 , Jun-2009
Dissertations and Theses Torgovitsky R. "Resampling methods for high-dimensional data and nonparametric regression with applications to brain imaging, bioinformatics, and sleep / circadian medicine." Dissertation, Harvard University, December 2008. , Dec-2008
Journal/Magazine covers Cohen DA, Wang W, Wyatt JK, Kronauer RE, Dijk DJ, Czeisler CA, Klerman EB. "Cover of online journal Science Translational Medicine for article, 'Uncovering residual effects of chronic sleep loss on human performance.'" Science Translational Medicine. 2010 Jan 13;2(14):14ra3. PubMed PMID: 20371466 http://stm.sciencemag.org/content/2/14.cover-expansion , Jan-2010
Project Title:  Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness in Space Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 06/05/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Klerman, Elizabeth B. M.D., Ph.D. / Brigham and Women's Hospital/Harvard Medical Center 
Address:  Department of Medicine 
Division of Sleep Medicine 
Boston , MA 02115-5804 
Email: ebklerman@hms.harvard.edu 
Phone: 617-732-8145  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham and Women's Hospital/Harvard Medical Center 
Joint Agency:  
Comments:  
Project Information: Grant/Contract No. NCC 9-58-HFP01603 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01603 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) BHP:Behavioral Health & Performance (archival in 2017)
Human Research Program Risks: (1) Sleep:Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload (IRP Rev F)
Human Research Program Gaps: (1) Sleep Gap 04:We need to identify indicators of individual vulnerabilities and resiliencies to sleep loss and circadian rhythm disruption, to aid with individualized countermeasure regimens, for autonomous, long duration and/or distance exploration missions (IRP Rev E)
(2) Sleep Gap 08:We need to develop individualized scheduling tools that predict the effects of sleep-wake cycles, light and other countermeasures on performance, and can be used to identify optimal (and vulnerable) performance periods during spaceflight (IRP Rev E)
Task Description: Objective neurobehavioral performance, subjective alertness, and sleep are critically important to astronaut and ground-based crew health and to ensure the success of space missions. Neurobehavioral performance and alertness are affected by changes in circadian rhythms, homeostatic sleep/wake regulation and sleep inertia, and the interactions of these processes. During space missions, circadian rhythms and sleep are disrupted, both for those in space and for those on Earth. Astronaut problems with sleep, circadian rhythms and performance have been reported. NASA data indicate that sleeping pills are among the most commonly used drugs in space. Therefore, it is imperative that schedules and countermeasures are designed to optimize individual performance, alertness, and quality sleep relative to operational requirements.

We have developed and validated a mathematical model of the human circadian pacemaker, performance and alertness that includes the key processes of circadian rhythms, sleep/wake homeostasis and sleep inertia. The software implementing this model has been used by NASA and consultants when designing light countermeasures for astronaut pre-launch schedules.

For our current NSBRI project, we have developed a mathematical method for optimal design of countermeasures and schedules after a change in timing of sleep, light or critical tasks. Our specific aims are to: (1) Replace the current assumption that an individual sleeps when scheduled to sleep, with probabilities of sleep and wake during those times; (2) Improve daily assessment of sleep and sleep disruption using actigraphy data; (3) Add statistical features including confidence limits to the predictions; (4) Update the software per astronaut and ground crew requests for specific features and reports. The basic mathematical work will focus on individual, rather than group, predictions and use novel non-linear mathematical and statistical measures. These projects address NASA's objectives to improve the design of individual countermeasures to reduce sleep disruption and improve performance and alertness in space and on Earth.

Research Impact/Earth Benefits: The development (1) of mathematical models of circadian rhythms, sleep, alertness and performance and (2) of software based on these models that aid in schedule design can improve performance and alertness and thereby effectiveness and public safety for people who work at night, on rotating schedules, on non-24-hr schedules or extended duty schedules (pilots, train and truck drivers, shift workers, health care workers, public safety officers, etc.). Attempting to sleep at adverse circadian phases is difficult and sleep efficiency is poor. Attempting to work at adverse circadian phases and/or after long durations of time awake results in poor worker performance and productivity, increased accidents and decreased safety for workers and for others affected by the workers. For example, the accidents at the Chernobyl and Three Mile Island nuclear reactors and the Exxon Valdez grounding all were partially caused by workers working at adverse circadian phases (~ 4 am). The mathematical modeling and the available Circadian Performance Simulation Software (CPSS) can be used to simulate and quantitatively evaluate different scenarios of sleep/wake schedules and light exposure to predict the resulting circadian phase and amplitude, subjective alertness and performance. CPSS has been requested by members of academia, government and industry (transportation (especially airline personnel), safety, medical, military). Its use could help produce improved schedules for working for people in space and on earth.

The software also now includes optimal countermeasure design, so that countermeasures can be planned for times of predicted poor performance and alertness. The schedule/countermeasure design program that allows a user to interactively design a schedule and to automatically design a mathematically optimal countermeasure regime (intensity, duration and placement). This will be valuable to those who schedule people who work at night, on rotating schedules, on non-24-hr schedules or extended duty schedules. Individuals can design countermeasures for their assigned work schedules so that their sleep and wake rhythms will be adjusted for optimal performance at desired times. In addition, if the countermeasure design includes shifting the circadian rhythms to be appropriately aligned with environmental time, then performance, alertness and sleep will all improve. Improving sleep duration and quality can also decrease the risk of accidents and errors, as well as cardiovascular, metabolic, immune and psychological pathologies.

The mathematical modeling has been used for basic scientific research. Inclusion of mathematical models in the planning process to optimize measures to be studied in experimental protocols enables more efficient use of research resources and directs new research. If the modeling of existing data is unsatisfactory, then the model assumptions need to be revised. This revision may include identification of a new physiological process not previously described. As an example, an additional component (non-linear response to ocular light stimuli) was added to the circadian rhythms component of our mathematical model to describe data collected in our clinical research facilities, even before the anatomic and physiologic basis of this component of the mathematical model was found. Later experiments validated this mathematical finding. The mathematical model had demonstrated that previously unknown additional physiological processes were involved.

The modeling work on the differential effects of different wavelength of light on circadian rhythms and alertness can be used for designing artificial (indoor) lighting systems that can maximize circadian or alerting response.

The mathematical modeling efforts and CPSS have also been used in educational programs and in the popular press to teach students and teachers about circadian rhythms and sleep and their effects on alertness and performance.

Task Progress & Bibliography Information FY2009 
Task Progress: For our first year, we have concentrated on Specific Aim 2, with preliminary work on the other Specific Aims.

Specific Aim 2 (Improve the assessment of sleep and sleep disruption through the development of an improved actigraphy-to-sleep/wake classification algorithm): We developed a new sleep-wake classification algorithm that has been tested on actigraphy data collected under various conditions. A new algorithm exploits the assumption that there exists an implicit bimodal distribution in the actigraphy time series and that the extraction of this can clearly segregate sleep and wake cycles. A statistical bimodal distribution is not possible to obtain directly from the time series due to the presence of both inflated zeros and over-dispersion that result in a zero-inflated negative binomial distribution. Therefore we have developed a new method by which bimodal distribution obtained can be indirectly related to sleep-wake epochs of the activity count data.

Specificity, sensitivity, accuracy and predictive value of sleep and wake are determined by comparing epoch by epoch of actigraph data with that of polysomnographic data to test the algorithm Both high specificity and sensitivity are obtained by the application of present algorithm; in contrast, most of the published algorithms have either high sensitivity or specificity, but not both. This algorithm also has high sensitivity and specificity using the data collected from two different instruments (Actiwatch and Motionlogger): therefore this algorithm works well irrespective of the instrument or the way data is collected.

As future work, actigraphy data collected under habitual conditions, under conditions of quiet extended wake (which is difficult to distinguish from sleep), under conditions of forced desynchrony of sleep/wake cycle and circadian rhythms (to explore the effect of circadian phase) and under conditions of extended sleep (which induces insomnia or quiet wake during scheduled sleep, which is also difficult to differentiate from sleep) will be determined to further test the performance of the algorithm and will be compared with other threshold algorithms. Two manuscripts of this work are in preparation.

Specific Aim 3 (Statistical modeling of individual circadian, sleep, performance and alertness parameters): We have begun the first step in this work by concentrating on statistical modeling of individual circadian parameters.

Specific Aim 4 (Work with NASA and NSBRI personnel to revise features of our current software to meet their specifications for administratively scheduling sleep, wake and countermeasure design to minimize fatigue and performance issues.): We have had discussions with NASA and NSBRI personnel to revise features of our current software to meet their specifications for administratively scheduling sleep, wake and countermeasure design to minimize fatigue and performance issues, as well as incorporating the models into other modeling work performed by NASA.

Bibliography Type: Description: (Last Updated: 02/16/2021) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Dead DA, Wyatt JK, Dijk D, Czeisler CA, Klerman EB. "Quantifying practice effects within groups and individuals: examples from a month long forced desynchrony protocol." Sleep 2008, 22nd Annual Meeting, Balitimore, MD, June 7-12, 2008.

Sleep. 2008;31(Suppl): A54. , Jun-2008

Abstracts for Journals and Proceedings St Hilaire MA, Klerman EB. "Robustness of parameters in a circadian and neurobehavioral performance and alertness model suggest trait-like characteristics of the homeostatic process." Sleep 2008, 22nd Annual Meeting, Balitimore, MD, June 7-12, 2008.

Sleep 2008:31(Suppl):A117. , Jun-2008

Abstracts for Journals and Proceedings St Hilaire MA, Klerman EB. "Pattern recognition algorithms to classify performance on the psychomotor vigilance task." 2009 International Conference on Fatigue Management in Transportation Operations: A Framework for Progress, Boston, MA, March 24-26, 2009.

2009 International Conference on Fatigue Management in Transportation Operations: A Framework for Progress, Abstract Book, March 2009. , Mar-2009

Abstracts for Journals and Proceedings Torgovitsky R, Wang W, De Gruttola V, Klerman EB. "Subject-specific evaluation of performance based on forced desynchrony data." 2009 International Conference on Fatigue Management in Transportation Operations: A Framework for Progress, Boston, MA, March 24-26, 2009.

2009 International Conference on Fatigue Management in Transportation Operations: A Framework for Progress, Abstract Book, March 2009. , Mar-2009

Project Title:  Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness in Space Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 06/02/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Klerman, Elizabeth B. M.D., Ph.D. / Brigham and Women's Hospital/Harvard Medical Center 
Address:  Department of Medicine 
Division of Sleep Medicine 
Boston , MA 02115-5804 
Email: ebklerman@hms.harvard.edu 
Phone: 617-732-8145  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Brigham and Women's Hospital/Harvard Medical Center 
Joint Agency:  
Comments:  
Project Information: Grant/Contract No. NCC 9-58-HFP01603 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01603 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) BHP:Behavioral Health & Performance (archival in 2017)
Human Research Program Risks: (1) Sleep:Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload (IRP Rev F)
Human Research Program Gaps: (1) Sleep Gap 04:We need to identify indicators of individual vulnerabilities and resiliencies to sleep loss and circadian rhythm disruption, to aid with individualized countermeasure regimens, for autonomous, long duration and/or distance exploration missions (IRP Rev E)
(2) Sleep Gap 08:We need to develop individualized scheduling tools that predict the effects of sleep-wake cycles, light and other countermeasures on performance, and can be used to identify optimal (and vulnerable) performance periods during spaceflight (IRP Rev E)
Task Description: Objective neurobehavioral performance, subjective alertness and sleep are critically important to astronaut and ground-based crew health and to ensure the success of space missions. Neurobehavioral performance and alertness are affected by changes in circadian rhythms, homeostatic sleep/wake regulation and sleep inertia, and the interactions of these processes.

During space missions, circadian rhythms and sleep are disrupted, both for those working in space and for those on Earth. Astronaut problems with sleep, circadian rhythms and performance have been reported, and NASA data indicate that sleeping pills are among the most commonly used drugs in space. Therefore, it is imperative that schedules and countermeasures are designed to optimize individual performance, alertness and quality sleep relative to operational requirements.

We have developed and validated a mathematical model of the human circadian pacemaker, performance and alertness that includes the key processes of circadian rhythms, sleep/wake homeostasis and sleep inertia. The software implementing this model has been used by NASA to design light countermeasures for astronaut pre-launch schedules. In our previous NSBRI project, we developed a mathematical method for optimal design of countermeasures and schedules after a change in timing of sleep, light or critical tasks.

Specific Aims

1. Replace the current assumption that an individual sleeps when scheduled to sleep, with probabilities of sleep and wake during those times;

2. Improve daily assessment of sleep and sleep disruption using actigraphy data;

3. Add statistical features including confidence limits to the predictions; and

4. Update the software per astronaut and ground crew requests for specific features and reports.

The basic mathematical work will focus on individual, rather than group, predictions and will use novel, non-linear mathematical and statistical measures. This project addresses NASA's objectives to improve the design of individual countermeasures to reduce sleep disruption and improve performance and alertness in space and on Earth.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2008 
Task Progress: New project for FY2008.

Bibliography Type: Description: (Last Updated: 02/16/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2008