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Project Title:  Ultra-Short Light Pulses as Efficient Countermeasures for Circadian Misalignment and Objective Performance and Subjective Alertness Decrements Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 08/01/2012  
End Date: 02/29/2016  
Task Last Updated: 07/20/2016 
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: 
Wang, Wei  Brigham and Women's Hospital 
Lockley, Steven  Brigham and Women's Hospital 
Project Information: Grant/Contract No. NCC 9-58-HFP02802 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NCC 9-58-HFP02802 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
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 05:We need to identify environmental specifications and operational regimens for using light to prevent and mitigate health and performance decrements due to sleep, circadian, and neurobehavioral disruption, for flight, surface and ground crews, during all phases of spaceflight operations (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date change to 2/29/2016 per NSBRI (Ed., 2/1/16)

NOTE: End date change to 12/31/2015 per NSBRI (Ed., 10/14/15)

NOTE: End date change to 9/30/2015 per NSBRI (Ed., 2/6/15)

Task Description: Lighting protocols have been recognized by NSBRI (National Space Biomedical Research Institute), NASA, and NIH (National Institutes of Health) as important countermeasures for circadian rhythm and sleep disruptions and their associated effects on performance and alertness for both crews in space and workers on Earth. The current light-based countermeasures involve one or more hours of bright light exposure. We have recently demonstrated significant circadian phase shifting with an ultra-short 2-minute bright light stimulus. The use of such a short duration stimulus as a countermeasure would significantly preserve the ability to work in the International Space Station (ISS) lighting environment and reduce crew resource requirements. We proposed to test the relative efficacy of both ultra-short and longer-duration light protocol countermeasures using the newly approved ISS lighting system to induce both adaptive circadian resetting and direct alerting effects. Experiments were conducted jointly with Dr. S. Lockley and his NSBRI project "The ISS Dynamic Lighting Schedule: An in-flight lighting countermeasure to facilitate circadian adaptation, improve sleep and enhance alertness and performance on the International Space Station." These studies will further our understanding of the physiologic mechanisms that mediate exposure-duration-dependent and wavelength-dependent effects of photic stimuli on circadian phase and performance. Furthermore, results from these experiments will be added to our validated physiologically-based mathematical models of light, sleep/wake and circadian rhythms effects on performance and alertness, including a software application used for determining the optimal timing of light exposure to be employed as a countermeasure for predicted times of poor performance and alertness. The experimental and modeling results will have direct Earth-based applications for workers on early-rising, night, or rotating schedules, as well as for people experiencing jet lag. The work directly addresses one of the NSBRI NASA Research Announcement (NRA) research objectives and two NASA Human Research Program Integrated Research Plan (IRP) Risks. This proposal will also address other NSBRI goals: training of future scientists, collaboration among NSBRI investigators, and a combination of basic science with space-based applications and potential commercial applications.

NOTE: Follow-on continues as a directed research project as "Ultra-Short Light Pulses as Efficient Countermeasures for Circadian Misalignment and Objective Performance and Subjective Alertness Decrements--HFP00006."

Research Impact/Earth Benefits: Light is the major environmental time cue that resets the circadian pacemaker in the the mammalian hypothalamus. Light information is captured exclusively by the eyes using specialized cells containing a blue-light sensitive photopigment. Each day the light-dark cycle resets the internal clock, which in turn synchronizes the physiology, psychology, and behavior controlled by the clock. Failure to receive this light-dark information, as experienced for example by totally blind individuals, causes the circadian pacemaker to revert to its endogenous non-24-hour period and possibly become desynchronized from the 24-hour light-dark cycle. Exposure to irregular light-dark cycles, as experienced for example by psychiatric patients with irregular sleep-wake cycles, can also disrupt circadian rhythms. Light also suppresses the hormone melatonin and has a direct arousal effect on the brain, improving alertness and performance. This property of light can be useful as a non-pharmacological treatment for fatigue in a number of conditions, and if timed appropriately, these effects can complement the circadian phase resetting effects of light, for example in treating shiftwork and jet-lag disorders, to help maintain alertness at the correct time and subsequently improve sleep. The results of our experiments in which gradual vs. slam-shift changes in schedule along with continuous or intermittent light exposure are tested for their effects on circadian rhythms, sleep, hormones, subjective alertness, and objective performance will be applicable to conditions such as jet lag, and shift-work or night-work. Millions of workers in the safety, security, transportation, healthcare, and industrial sectors are affected by these conditions yearly, with effects on health and safety.

The development of (i) mathematical models of circadian rhythms, sleep, alertness, and performance, and (ii) 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, healthcare 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 (Federal Aviation Administration) 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 NASA, 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 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. NIRS monitoring may be useful in identifying individuals who might be at increased risk of sleep-related errors and occupational injuries. The cost-effective and minimally intrusive NIRS (Near Infrared Spectroscopy) assessment of regional brain activity may be applicable in personnel in safety-sensitive occupations, for better understanding the physiology underlying attentional failures, and for developing countermeasures for these failures.

Task Progress & Bibliography Information FY2016 
Task Progress: 1) Experimental: We began our recruitment efforts in Jan 2013 and we have successfully completed all planned studies. Thirty participants have completed the protocol out of whom 18 (9 females) were studied in the first (advance) arm of Experiment 1a and 12 (6 females) in the second (delay) arm of Experiment 1b. A total of 5 participants were admitted but then disempanelled from the study. We then studied an additional 6 participants (3 females), none disempanelled, under the Experiment 2 (intermittent light exposure condition).

2) Modeling: The mathematical model is continuing to be updated with information from the experimental work and data from the Division of Sleep and Circadian Disorders database. The mathematical model was also used to inform the design of Experiment 1, including to optimize the timing of the lighting to maximize circadian phase shifts. We have also continued development of the linked circadian, sleep, and performance model to include the use of multiple countermeasures (e.g., sleep, light, pharmaceuticals) in tandem. These additions will greatly improve the utility of the models in real-world conditions, including long duration spaceflights, where chronic sleep restriction is common. The significance of the modeling will be better understanding and prediction of the effects of light on human circadian rhythms, sleep, hormones, performance, and alertness. In addition, we have developed a new, physiologically-based model of the effects of chronic sleep restriction. This new model has been designed so that it can be easily integrated within our existing linked model.

3) NIRS: Additionally, prefrontal cortex hemodynamic responses to PVT stimuli and sleep are monitored using Near Infrared Spectroscopy (NIRS). We have monitored via NIRS from 6 participants in the first experiment and 7 in the second. Progress also addresses other goals within NSBRI: training of future scientists, collaboration between and among NSBRI teams, combination of basic science, space-based applications, and other, potentially commercial, applications.

NOTE: Follow-on continues as a directed research project as "Ultra-Short Light Pulses as Efficient Countermeasures for Circadian Misalignment and Objective Performance and Subjective Alertness Decrements--HFP00006." See that project for subsequent reporting.

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

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Sano A, Phillips AJ, Taylor S, McHill AW, O'Brien C, Buie J, Hidalgo CA, Barger L, Czeisler CA, Klerman EB, Picard RW. "Influence of Sleep Regularity on Self-Reported Mental Health and Wellbeing." SLEEP 2016, 30th Annual Meeting of the Associated Professional Sleep Societies, Denver, CO, June 11-15, 2016.

Sleep. 2016;39(Abstract Suppl):A68. Abstract 0183. , Jun-2016

Abstracts for Journals and Proceedings Phillips AJ, Tracy M, Klerman EB. "A model-based analysis of light-induced circadian arrhythmia in the Siberian hamster." SRBR 2016. 15th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Palm Harbor, FL, May 21-25, 2016.

Program and Abstracts. SRBR 2016. 15th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Palm Harbor, FL, May 21-25, 2016. Abstract M87, p. 289. , May-2016

Abstracts for Journals and Proceedings McHill AW, McMullan C, Hull JT, Scheer FAJL, Czeisler CA, Klerman EB. "Chronic Sleep Restriction Increases the Change in Systolic Blood Pressure between Circadian Night and Day" SRBR 2016. 15th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Palm Harbor, FL, May 21-25, 2016.

Program and Abstracts. SRBR 2016. 15th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Palm Harbor, FL, May 21-25, 2016. Abstract S113, p. 229-230. , May-2016

Abstracts for Journals and Proceedings McHill AW, Hull JT, Wang W, Czeisler CA, Klerman EB. "Deterioration of neurobehavioral performance during chronic sleep restriction in the absence of extended wake episodes." SLEEP 2016, 30th Annual Meeting of the Associated Professional Sleep Societies, Denver, CO, June 11-15, 2016.

Sleep. 2016;39(Abstract Suppl):A92. Abstract 0253. , Jun-2016

Abstracts for Journals and Proceedings Wang W, Liu H, Duffy JF, Cohen A, Hull JT, Czeisler CA, Klerman EB. "Comparing subjective and objective sleep assessments." SLEEP 2016, 30th Annual Meeting of the Associated Professional Sleep Societies, Denver, CO, June 11-15, 2016.

Sleep. 2016;39(Abstract Suppl):A361. Abstract 1009. , Jun-2016

Abstracts for Journals and Proceedings Clerx WM, Phillips AJ, Lockley SW, O'Brien CS, Klerman EB, Czeisler CA. "Irregular sleep in college students." SLEEP 2015, 29th Annual Meeting of the Associated Professional Sleep Societies, Seattle, WA, June 6-10, 2015.

Sleep. 2015;38(Abstract Suppl):A78-A79. Abstract 0214. , Jun-2015

Abstracts for Journals and Proceedings Elmenhorst E-M, Wang W, Gronfier C, Klerman EB. "Performance and alertness after combined exposure to chronic and acute sleep loss and circadian misalignment." Worldsleep 2015. 7th World Congress of the World Sleep Federation, Istanbul, Turkey, October 31-November 3, 2015.

Worldsleep 2015. 7th World Congress of the World Sleep Federation, Istanbul, Turkey, October 31-November 3, 2015. , Nov-2015

Abstracts for Journals and Proceedings Schneider J, Saenz-Otero, Klerman E, Stirling L. "A Pilot Study of Fatigue and Situation Awareness During Simulated Small Satellite Operations." 87th Aerospace Medical Association Annual Meeting, Atlantic City, NJ, April 24-28, 2016.

Aerospace Medicine and Human Performance. 2016 Mar;87(3). , Mar-2016

Abstracts for Journals and Proceedings Lane JM, Chang A, Consortium C, Aeschbach D, Cain SW, Czeisler CA, Klerman EB, Lockley SW, St. Hilaire M Shea SA, Duffy JF, Buxton OM, Redline S, Scheer FA, Saxena R. "Impact of common variation at diabetes trait loci MTNR1B and CRY2 on sleep, circadian, and melatonin physiology." SLEEP 2015, 29th Annual Meeting of the Associated Professional Sleep Societies, Seattle, WA, June 6-10, 2015.

Sleep. 2015;38(Abstract Suppl):A5-A6. Abstract 0013. , Jun-2015

Abstracts for Journals and Proceedings Lee ML, Strangman GE, Hull JT, Kamath TV, Wang W, Ivkovic V, Zhang Q, Czeisler CA, Klerman EB. "Prefrontal brain response to neurobehavioral testing is correlated with cognitive performance." SLEEP 2015, 29th Annual Meeting of the Associated Professional Sleep Societies, Seattle, WA, June 6-10, 2015.

Sleep. 2015;38(Abstract Suppl):A115. Abstract 0320. , Jun-2015

Abstracts for Journals and Proceedings Lee ML, Strangman GE, Hull JT, Kamath TV, Wang W, Ivkovic V, Zhang Q, Czeisler C, Klerman EB. "Prefrontal brain response to neurobehavioral testing is correlated with cognitive performance." 2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015.

2015 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 13-15, 2015. , Jan-2015

Abstracts for Journals and Proceedings Mankowski PW, Phillips AJ, Klerman EB. "New methods for defining NREM/REM sleep cycles in human sleep episodes." SLEEP 2015, 29th Annual Meeting of the Associated Professional Sleep Societies, Seattle, WA, June 6-10, 2015.

Sleep. 2015;38(Abstract Suppl):A137. Abstract 0382. , Jun-2015

Abstracts for Journals and Proceedings Phillips AJK, Swaminathan K, Klerman EB. "Are individual differences in sleep and circadian timing amplitude by use of artificial light?" Worldsleep 2015. 7th World Congress of the World Sleep Federation, Istanbul, Turkey, October 31-November 3, 2015.

Worldsleep 2015. 7th World Congress of the World Sleep Federation, Istanbul, Turkey, October 31-November 3, 2015. , Nov-2015

Articles in Peer-reviewed Journals Sano A, Yu AZ, McHill AW, Phillips AJ, Taylor S, Jaques N, Klerman EB, Picard RW. "Prediction of Happy-Sad mood from daily behaviors and previous sleep history." Conf Proc IEEE Eng Med Biol Soc. 2015;2015:6796-9. http://dx.doi.org/10.1109/EMBC.2015.7319954 ; PubMed PMID: 26737854; PubMed Central PMCID: PMC4768795 (2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Milan, Italy, August 25-29, 2015.) , Aug-2015
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 Lane JM, Chang AM, Bjonnes AC, Aeschbach D, Anderson C, Cade BE, Cain SW, Czeisler CA, Gharib SA, Gooley JJ, Gottlieb DJ, Grant SF, Klerman EB, Lauderdale DS, Lockley SW, Munch M, Patel S, Punjabi NM, Rajaratnam SM, Rueger M, St Hilaire MA, Santhi N, Scheuermaier K, Van Reen E, Zee PC, Shea SA, Duffy JF, Buxton OM, Redline S, Scheer FA, Saxena R. "Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology." Diabetes. 2016 Jun;65(6):1741-51. Epub 2016 Feb 11. http://dx.doi.org/10.2337/db15-0999 ; PubMed PMID: 26868293; PubMed Central PMCID: PMC4878414 , Jun-2016
Articles in Peer-reviewed Journals Vijayan S, Klerman EB, Adler GK, Kopell NJ. "Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia." J Neurophysiol. 2015 Sep;114(3):1923-30. http://dx.doi.org/10.1152/jn.00280.2015 ; PubMed PMID: 26245315; PubMed Central PMCID: PMC4575971 , Sep-2015
Articles in Peer-reviewed Journals Shaw ND, McHill AW, Schiavon M, Kangarloo T, Mankowski PW, Cobelli C, Klerman EB, Hall JE. "Effect of slow-wave sleep disruption on metabolic parameters in adolescents." Sleep. 2016 Aug 1;39(8):1591-9. http://dx.doi.org/10.5665/sleep.6028 ; PubMed PMID: 27166229; PubMed Central PMCID: PMC4945319 , Aug-2016
Articles in Peer-reviewed Journals Klerman EB, Beckett SA, Landrigan CP. "Applying mathematical models to predict resident physician performance and alertness on traditional and novel work schedules." BMC Med Educ. 2016 Sep 13;16(1):239. http://dx.doi.org/10.1186/s12909-016-0751-9 ; PubMed PMID: 27623842; PubMed Central PMCID: PMC5022151 , Sep-2016
Articles in Peer-reviewed Journals Bianchi MT, Phillips AJ, Wang W, Klerman EB. "Statistics for sleep and biological rhythms research: From distributions and displays to correlation and causation." J Biol Rhythms. 2017 Feb;32(1):7-17. Epub 2016 Oct 25. https://doi.org/10.1177/0748730416670050 ; PubMed PMID: 27836938; PubMed Central PMCID: PMC5501416 , Feb-2017
Articles in Peer-reviewed Journals Klerman EB, Wang W, Phillips AJ, Bianchi MT. "Statistics for sleep and biological rhythms research: Longitudinal analysis of biological rhythms data." J Biol Rhythms. 2017 Feb;32(1):18-25. Epub 2016 Oct 25. https://doi.org/10.1177/0748730416670051 ; PubMed PMID: 27836939; PubMed Central PMCID: PMC5483995 , Feb-2017
Articles in Peer-reviewed Journals Swaminathan K, Klerman EB, Phillips AJK. "Are individual differences in sleep and circadian timing amplified by use of artificial light sources?" J Biol Rhythms. 2017 Apr;32(2):165-76. http://doi.org/10.1177/0748730417699310 ; PubMed PMID: 28367676 , Apr-2017
Articles in Peer-reviewed Journals Rahman SA, St Hilaire MA, Chang AM, Santhi N, Duffy JF, Kronauer RE, Czeisler CA, Lockley SW, Klerman EB. "Circadian phase resetting by a single short-duration light exposure." JCI Insight. 2017 Apr 6;2(7):e89494. https://doi.org/10.1172/jci.insight.89494 ; PubMed PMID: 28405608; PubMed Central PMCID: PMC5374060 , Apr-2017
Articles in Peer-reviewed Journals Phillips AJK, Clerx WM, O'Brien CS, Sano A, Barger LK, Picard RW, Lockley SW, Klerman EB, Czeisler CA. "Irregular sleep/wake patterns are associated with poorer academic performance and delayed circadian and sleep/wake timing." Sci Rep. 2017 Jun 12;7(1):3216. https://doi.org/10.1038/s41598-017-03171-4 ; PubMed PMID: 28607474; PubMed Central PMCID: PMC5468315 , Jun-2017
Articles in Peer-reviewed Journals Phillips AJK, Klerman EB, Butler JP. "Modeling the adenosine system as a modulator of cognitive performance and sleep patterns during sleep restriction and recovery." PLoS Comput Biol. 2017 Oct 26;13(10):e1005759. eCollection 2017 Oct. https://doi.org/10.1371/journal.pcbi.1005759 ; PubMed PMID: 29073206; PubMed Central PMCID: PMC5675465 , Oct-2017
Articles in Peer-reviewed Journals McHill AW, Phillips AJ, Czeisler CA, Keating L, Yee K, Barger LK, Garaulet M, Scheer FA, Klerman EB. "Later circadian timing of food intake is associated with increased body fat." Am J Clin Nutr. 2017 Nov;106(5):1213-9. Epub 2017 Sep 6. https://doi.org/10.3945/ajcn.117.161588 ; PubMed PMID: 28877894; PubMed Central PMCID: PMC5657289 , Nov-2017
Articles in Peer-reviewed Journals Gottlieb DJ, Ellenbogen JM, Bianchi MT, Czeisler CA. "Sleep deficiency and motor vehicle crash risk in the general population: A prospective cohort study." BMC Med. 2018 Mar 20;16(1):44. https://doi.org/10.1186/s12916-018-1025-7 ; PubMed PMID: 29554902; PubMed Central PMCID: PMC5859531 , Mar-2018
Articles in Peer-reviewed Journals Rahman SA, St Hilaire MA, Gronfier C, Chang AM, Santhi N, Czeisler CA, Klerman EB, Lockley SW. "Functional decoupling of melatonin suppression and circadian phase resetting in humans." J Physiol. 2018 Jun;596(11):2147-57. https://doi.org/10.1113/JP275501 ; PubMed PMID: 29707782; PubMed Central PMCID: PMC5983136 , Jun-2018
Articles in Peer-reviewed Journals McHill AW, Hull JT, Wang W, Czeisler CA, Klerman EB. "Chronic sleep curtailment, even without extended (>16-h) wakefulness, degrades human vigilance performance." Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):6070-5. https://doi.org/10.1073/pnas.1706694115 ; PubMed PMID: 29784810; PubMed Central PMCID: PMC6003377 , Jun-2018
Articles in Peer-reviewed Journals McHill AW, Hull JT, McMullan CJ, Klerman EB. "Chronic insufficient sleep has a limited impact on circadian rhythmicity of subjective hunger and awakening fasted metabolic hormones." Front Endocrinol (Lausanne). 2018 Jun 12;9:319. eCollection 2018. https://doi.org.10.3389/fendo.2018.00319 ; PubMed PMID: 29946297; PubMed Central PMCID: PMC6005823 , Jun-2018
Articles in Peer-reviewed Journals McHill AW, Hull JT, Cohen DA, Wang W, Czeisler CA, Klerman EB. "Chronic sleep restriction greatly magnifies performance decrements immediately after awakening." Sleep. 2019 May 1;42(5). pii: zsz032. https://doi.org/10.1093/sleep/zsz032 ; PubMed PMID: 30722039 ; PubMed Central PMCID: PMC6519907 , May-2019
Articles in Peer-reviewed Journals McHill AW, Czeisler CA, Phillips AJK, Keating L, Barger LK, Garaulet M, Scheer F, Klerman EB. "Caloric and macronutrient intake differ with circadian phase and between lean and overweight young adults." Nutrients. 2019 Mar 11;11(3):587. https://doi.org/10.3390/nu11030587 ; PubMed PMID: 30862011 , Mar-2019
Articles in Peer-reviewed Journals Chang AM, Duffy JF, Buxton OM, Lane JM, Aeschbach D, Anderson C, Bjonnes AC, Cain SW, Cohen DA, Frayling TM, Gooley JJ, Jones SE, Klerman EB, Lockley SW, Munch M, Rajaratnam SMW, Rueger M, Rutter MK, Santhi N, Scheuermaier K, Van Reen E, Weedon MN, Czeisler CA, Scheer F, Saxena R. "Chronotype genetic variant in PER2 is associated with intrinsic circadian period in humans." Sci Rep. 2019 Mar 29;9(1):5350. Published online 29 March 2019. https://doi.org/10.1038/s41598-019-41712-1 ; PubMed PMID: 30926824; PubMed Central PMCID: PMC6440993 , Mar-2019
Articles in Peer-reviewed Journals Kronauer RE, St Hilaire MA, Rahman SA, Czeisler CA, Klerman EB. "An exploration of the temporal dynamics of circadian resetting responses to short- and long-duration light exposures: Cross-species consistencies and differences." J Biol Rhythms. 2019 Oct;34(5):497-514. Epub 2019 Aug 1. https://doi.org/10.1177/0748730419862702 ; PubMed PMID: 31368391; PMCID: PMC7363039 , Oct-2019
Articles in Peer-reviewed Journals Barger LK, Sullivan JP, Blackwell T, O'Brien CS, St Hilaire MA, Rahman SA, Phillips AJK, Qadri S, Wright KP, Segar JL, McGuire JK, Vitiello MV, de la Iglesia HO, Poynter SE, Yu PL, Zee P, Sanderson AL, Halbower AC, Lockley SW, Landrigan CP, Stone KL, Czeisler CA. "Effects on resident work hours, sleep duration and work experience in a Randomized Order Safety Trial Evaluating Resident-physician Schedules (ROSTERS)." Sleep. 2019 Aug 1;42(8):zsz110. https://doi.org/10.1093/sleep/zsz110 ; PubMed PMID: 31106381; PubMed Central PMCID: PMC6685326 , Aug-2019
Articles in Peer-reviewed Journals Fischer D, McHill AW, Sano A, Picard RW, Barger LK, Czeisler CA, Klerman EB, Phillips AJK. "Irregular sleep and event schedules are associated with poorer self-reported well-being in US college students." Sleep. 2020 Jun 15;43(6):zsz300. https://doi.org/10.1093/sleep/zsz300 ; PMID: 31837266; PMCID: PMC7294408 , Jun-2020
Articles in Peer-reviewed Journals Cochrane C, Ba D, Klerman EB, St Hilaire MA. "An ensemble mixed effects model of sleep loss and performance." J Theor Biol. 2021 Jan 21;509:110497. Available online 2020 Sep 20. https://doi.org/10.1016/j.jtbi.2020.110497 ; PMID: 32966825 , Jan-2021
Articles in Peer-reviewed Journals McHill AW, Hilditch CJ, Fischer D, Czeisler CA, Garaulet M, Scheer F, Klerman EB. "Stability of the timing of food intake at daily and monthly timescales in young adults." Sci Rep. 2020 Nov 30;10(1):20849. https://doi.org/10.1038/s41598-020-77851-z ; PMID: 33257712; PMCID: PMC7705740 , Nov-2020
Awards Gupta M, Beckett SA, Klerman EB. "Best paper ('On-line EEG Denoising Using Correlated Sparse Recovery.') prize for IEEE 2016 10th International Symposium on Medical Information and Communication Technology (ISMICT), Worcester, MA, March 20-23, 2016." Mar-2016
Awards International Space Station Flexible Lighting Team. "NASA Johnson Space Center (JSC) Director's Innovation Award, February 2015." Feb-2015
NASA Technical Documents Klerman E, Dinges D, Ohnesorge K, Whitmire A. "Summary Report: Sleep on Earth and in Space: Risk Factors, Health and Performance Outcomes, and Countermeasures." Washington, DC : NASA Headquarters, 2015. 20 p. NASA/TM-2015-218588. , Aug-2015
Papers from Meeting Proceedings Gupta M, Beckett SA, Klerman EB. "On-line EEG Denoising Using Correlated Sparse Recovery." IEEE 2016 10th International Symposium on Medical Information and Communication Technology (ISMICT), Worcester, MA, March 20-23, 2016.

Proceedings of the IEEE 2016 10th International Symposium on Medical Information and Communication Technology (ISMICT), Worcester, MA, March 20-23, 2016. http://dx.doi.org/10.1109/ISMICT.2016.7498892 , Mar-2016

Papers from Meeting Proceedings Sano A, Phillips AJK, Zhao A, McHill AW, Taylor S, Jaques N, Czeisler CA, Klerman EB, Picard RW. "Recognizing academic performance, sleep quality, stress level, and mental health using personality traits, wearable sensors, and mobile phones." 2015 IEEE 12th International Conference on Wearable and Implantable Body Sensor Networks (BSN), Cambridge, MA, June 9-12, 2015.

2015 IEEE 12th International Conference on Wearable and Implantable Body Sensor Networks (BSN), Cambridge, MA, June 9-12, 2015. http://dx.doi.org/10.1109/BSN.2015.7299420 , Jun-2015

Project Title:  Ultra-Short Light Pulses as Efficient Countermeasures for Circadian Misalignment and Objective Performance and Subjective Alertness Decrements Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 08/01/2012  
End Date: 02/29/2016  
Task Last Updated: 09/08/2014 
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: 
Wang, Wei  Brigham and Women's Hospital 
Lockley, Steven  Brigham and Women's Hospital 
Project Information: Grant/Contract No. NCC 9-58-HFP02802 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NCC 9-58-HFP02802 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
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 05:We need to identify environmental specifications and operational regimens for using light to prevent and mitigate health and performance decrements due to sleep, circadian, and neurobehavioral disruption, for flight, surface and ground crews, during all phases of spaceflight operations (IRP Rev E)
Flight Assignment/Project Notes: NOTE: End date change to 2/29/2016 per NSBRI (Ed., 2/1/16)

NOTE: End date change to 12/31/2015 per NSBRI (Ed., 10/14/15)

NOTE: End date change to 9/30/2015 per NSBRI (Ed., 2/6/15)

Task Description: Lighting protocols have been recognized by NSBRI (National Space Biomedical Research Institute), NASA, and NIH (National Institutes of Health) as important countermeasures for circadian rhythm and sleep disruptions and their associated effects on performance and alertness for both crews in space and workers on Earth. The current light-based countermeasures involve one or more hours of bright light exposure. We have recently demonstrated significant circadian phase shifting with an ultra-short 2-minute bright light stimulus. The use of such a short duration stimulus as a countermeasure would significantly preserve the ability to work in the International Space Station (ISS) lighting environment and reduce crew resource requirements. We propose to test the relative efficacy of both ultra-short and longer-duration light protocol countermeasures using the newly approved ISS lighting system to induce both adaptive circadian resetting and direct alerting effects. Experiments will be conducted jointly with Dr. S. Lockley and his NSBRI project "The ISS Dynamic Lighting Schedule:An in-flight lighting countermeasure to facilitate circadian adaptation, improve sleep and enhance alertness and performance on the International Space Station." These studies will further our understanding of the physiologic mechanisms that mediate exposure-duration-dependent and wavelength-dependent effects of photic stimuli on circadian phase and performance. Furthermore, results from these experiments will be added to our validated physiologically based mathematical models of light, sleep/wake, and circadian rhythms effects on performance and alertness, including a software application used for determining the optimal timing of light exposure to be employed as a countermeasure for predicted times of poor performance and alertness. The experimental and modeling results will have direct Earth-based applications for workers on early-rising, night, or rotating schedules, as well as for people experiencing jet lag. The proposed work directly addresses one of the NSBRI NASA Research Announcement (NRA) research objectives and two NASA Human Research Program Integrated Research Plan (IRP) Risks. This proposal will also address other NSBRI goals: training of future scientists, collaboration among NSBRI investigators, and a combination of basic science with space-based applications and potential commercial applications.

Research Impact/Earth Benefits: Light is the major environmental time cue that resets the circadian pacemaker in the Suprachiasmatic Nucleus (SCN) of the mammalian hypothalamus. Light information is captured exclusively by the eyes using specialized intrinsically photosensitive retinal ganglion cells containing the novel blue-light sensitive photopigment melanopsin and transduced directly to the SCN via a dedicated neural pathway, the retinohypothalamic tract. Each day the light-dark cycle resets the internal clock, which in turn synchronizes the physiology, psychology, and behavior controlled by the clock. Failure to receive this light-dark information, as experienced for example by totally blind individuals, causes the circadian pacemaker to revert to its endogenous non-24-hour period and possibly become desynchronized from the 24-hour light-dark cycle. Exposure to irregular light-dark cycles, as experienced for example by psychiatric patients with irregular sleep-wake cycles, can also disrupt circadian rhythms. In addition to its circadian resetting and melatonin suppression effects, light has a direct arousal effect on the brain, improving alertness and performance. This property of light can be useful as a non-pharmacological treatment for fatigue in a number of conditions, and if timed appropriately, these effects can complement the circadian phase resetting effects of light, for example in treating shiftwork and jet-lag disorders, to help maintain alertness at the correct time and subsequently improve sleep. The results of our experiments in which gradual vs. slam-shift changes in schedule along with continuous or intermittent light exposure are tested for their effects on circadian rhythms, sleep, hormones, subjective alertness, and objective performance will be applicable to conditions such as jet lag, and shift-work or night-work. Millions of workers in the safety, security, transportation, healthcare, and industrial sectors are affected by these conditions yearly, with effects on health and safety. The development of (i) mathematical models of circadian rhythms, sleep, alertness, and performance, and (ii) 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, healthcare 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 Federal Aviation Administration (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 NASA, 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 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 FY2014 
Task Progress: 1) Experimental: We began our recruitment efforts in Jan 2013 and to date we have screened 81 potential participants, 32 participants have been excluded based on study inclusion/exclusion criteria, 18 participants have completed the study, and an additional 10 participants are completing the screening portion of the study. One participant was disempanelled from the study. We expect to complete studies in an additional 18 participants by the end of July 2015. Participants are randomized to either the gradual or slam shift arms of the study on the day of admission. The dynamic lighting is generated using the Solid State Lighting Module for Research (SSLM-R), a functional ISS lighting analog that mimics both the geometry of the light sources aboard ISS and the light source and spectra that will eventually be deployed.

Primary outcome measures of the study include: a) Circadian phase shifts: Shift in endogenous circadian phase (Dim Light Melatonin Onset; DLMO) between initial and final phase assessment. b) Cognitive performance: Subjective sleepiness measured using the Karolinska Sleepiness Scale. Objective measures of alertness include the visual and auditory psychomotor vigilance tests (PVT) and EEG correlates of alertness. c) Sleep structure and architecture: Polysomnographic assessment of sleep structure and architecture including latency and efficiency. Additionally, prefrontal cortex hemodynamic responses to PVT stimuli and sleep are monitored using Near Infrared Spectroscopy (NIRS). We have monitored via NIRS from 6 participants. We expect to monitor an additional 18 participants by the end of July 2015.

2) Modeling: The mathematical model is continuing to be updated with information from the experimental work and data from the Division of Sleep and Circadian Disorders database. The mathematical model was also used to inform the design of Experiment 1, including to optimize the timing of the lighting to maximize circadian phase shifts. We have also continued development of the linked circadian, sleep, and performance model to include the use of multiple countermeasures (e.g., sleep, light, pharmaceuticals) in tandem. These additions will greatly improve the utility of the models in real-world conditions, including long duration spaceflights, where chronic sleep restriction is common. The significance of the modeling will be better understanding and prediction of the effects of light on human circadian rhythms, sleep, hormones, performance, and alertness. In addition, we have developed a new, physiologically based model of the effects of chronic sleep restriction. This new model has been designed so that it can be easily integrated within our existing linked model. Progress also addresses other goals within NSBRI: training of future scientists, collaboration between and among NSBRI teams, combination of basic science, space based applications and other, potentially commercial, applications.

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

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Bermudez E, Klerman EB, Cohen DA, Wyatt JK, Czeisler CA, Phillips AJK. "The Relationship Between Subjective Alertness and Objective Performance during Chronic Sleep Restriction." SLEEP 2014, Minneapolis MN, May 31-June 4, 2014.

Sleep. 2014;37(Abstract Suppl):A84. Abstract 0232. , Jun-2014

Abstracts for Journals and Proceedings Clerx WM, Phillips AJK, Lockley SW, O'Brien CS, Klerman EB, Czeisler CA. "Impact of irregularity of sleep-wake schedules on circadian phase and amplitude in college undergraduates." SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014.

Program and Abstracts. SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014. Abstract P187, p. 228. http://srbr.org/wp-content/uploads/2015/02/SRBR2014ShortProgramv4.pdf , Jun-2014

Abstracts for Journals and Proceedings Cohen DA, Wang W, Wyatt JK, Czeisler CA, Klerman EB. "Sleep Inertia during Chronic Sleep Restriction Is Affected by Circadian Phase, Length of Time Awake, and Duration of Sleep Restriction." SLEEP 2014, Minneapolis MN, May 31-June 4, 2014.

Sleep. 2014;37(Abstract Suppl):A86. Abstract 0239. , Jun-2014

Abstracts for Journals and Proceedings Lee ML, Strangman GE, Hull JT, Rahman SA, Lockley SW, Ivkovic V, Zhang Q, Klerman EB. "Assessing the Impact of Chronic Sleep Restriction and Acute Sleep Deprivation on Performance-Associated Regional Brain Activation using Near Infrared Spectroscopy." 2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014.

2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014. http://www.hou.usra.edu/meetings/hrp2014/pdf/3284.pdf , Feb-2014

Abstracts for Journals and Proceedings Lee ML, Strangman GE, Hull JT, Rahman SA, Lockley SW, Ivkovic V, Zhang Q, Klerman EB. "Assessing the Impact of Chronic Sleep Restriction and Acute Sleep Deprivation on Performance-Associated Regional Brain Activation using Near Infrared Spectroscopy." SLEEP 2014, Minneapolis MN, May 31-June 4, 2014.

Sleep. 2014;37(Abstract Suppl):A82-A83. Abstract 0228. , Jun-2014

Abstracts for Journals and Proceedings Lee ML, Strangman GE, Hull JT, Kamath T, Rahman SA, Lockley SW, Lockhandwala.J, Zhang Q, Czeisler C, Klerman EB. "Assessing the Impact of Chronic Sleep Restriction and Acute Sleep Deprivation on Performance-Associated Regional Brain Activation using Near Infrared Spectroscopy." SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014.

Program and Abstracts. SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014. Abstract P10, p. 122. http://srbr.org/wp-content/uploads/2015/02/SRBR2014ShortProgramv4.pdf , Jun-2014

Abstracts for Journals and Proceedings Mankowski P, Phillips AJP, Klerman EB. "Robust Methods for Scoring NREM/REM Sleep Cycles in Complex Human Sleep Episodes." SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014.

Program and Abstracts. SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014. Abstract P213, p. 243. http://srbr.org/wp-content/uploads/2015/02/SRBR2014ShortProgramv4.pdf , Jun-2014

Abstracts for Journals and Proceedings Phillips AJK, Butler JP, St. Hilaire MA, Klerman EB. "Dynamics of an adenosine-receptor-based model of sleep homeostasis for acute and chronic sleep restriction." SLEEP 2014, Minneapolis MN, May 31-June 4, 2014.

Sleep. 2014;37(Abstract Suppl):A92-A93. Abstract 0257. , Jun-2014

Abstracts for Journals and Proceedings Phillips AJK, St Hilaire MA, Butler JP, Klerman EB. "Modeling the Effects of Chronic Sleep Restriction and Circadian Rhythms on Sleep, Performance, and Alertness." 2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014.

2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014. http://www.hou.usra.edu/meetings/hrp2014/pdf/3273.pdf , Feb-2014

Abstracts for Journals and Proceedings Rahman SA, St Hilaire M, Flynn-Evans EE, Barger LK, Brainard GC, Czeisler CA, Lockley SW. "The ISS dynamic lighting schedule: An in-flight lighting countermeasure to facilitate circadian adaptation, improve sleep and enhance alertness and performance on the International Space Station." 2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014.

2014 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014. http://www.hou.usra.edu/meetings/hrp2014/pdf/3181.pdf , Feb-2014

Abstracts for Journals and Proceedings Rahman SA, St Hilaire MA, Chang AM, Santhi N, Gronfier C, Kronauer RE, Czeisler CA, Klerman EB, Lockley SW. "Functional decoupling of melatonin supression and circadian phase resetting in humans." SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014.

Program and Abstracts. SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014. Abstract P126, p. 190-191. http://srbr.org/wp-content/uploads/2015/02/SRBR2014ShortProgramv4.pdf , Jun-2014

Abstracts for Journals and Proceedings Rahman SA, St Hilaire MA, Lockley SW, Klerman EB. "The effect of ultra short duration light pulses on the human circadian pacemaker." SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014.

Program and Abstracts. SRBR 2014. 14th Biennial Meeting, Society for Research on Biological Rhythms (SRBR), Big Sky, Montana, June 14-18, 2014. Abstract P153, p. 207. http://srbr.org/wp-content/uploads/2015/02/SRBR2014ShortProgramv4.pdf , Jun-2014

Abstracts for Journals and Proceedings Wang W, Duffy JF, Czeisler CA, Klerman EB. "Sex Differences in Sleep Quantified Using Survival Analyses of Sleep and Wake Bouts: A Meta-Analysis across Forced Desynchrony Protocols." SLEEP 2014, Minneapolis MN, May 31-June 4, 2014.

Sleep. 2014;37(Abstract Suppl):A46. Abstract 0126. , Jun-2014

Articles in Peer-reviewed Journals Faghih RT, Dahleh MA, Adler GK, Klerman EB, Brown EN. "Deconvolution of serum cortisol levels by using compressed sensing." PLoS One. 2014 Jan 28;9(1):e85204. eCollection 2014. http://dx.doi.org/10.1371/journal.pone.0085204 ; PubMed PMID: 24489656; PubMed Central PMCID: PMC3904842 , Jan-2014
Articles in Peer-reviewed Journals Phillips AJ, Fulcher BD, Robinson PA, Klerman EB. "Mammalian rest/activity patterns explained by physiologically based modeling." PLoS Comput Biol. 2013 Sep;9(9):e1003213. http://dx.doi.org/10.1371/journal.pcbi.1003213 ; PubMed PMID: 24039566; PubMed Central PMCID: PMC3764015 , Sep-2013
Awards Klerman E. "Elected to International Academy of Astronautics as Corresponding Member for Section 3 Life Sciences, July 2013." Jul-2013
Books/Book Chapters Alameddine Y, Klerman EB, Bianchi MT. "Caffeine and Naps as Countermeasures for Sleep Loss." in "Sleep Deprivation and Disease: Effects on the Body, Brain and Behavior." Ed. M.T. Bianchi. New York : Springer Publishers, 2014. p. 231-242. http://dx.doi.org/10.1007/978-1-4614-9087-6_17 , Jan-2014
Books/Book Chapters Klerman EB, Bianchi MT. "Methods for Human Sleep Deprivation Experiments." in "Sleep Deprivation and Disease: Effects on the Body, Brain and Behavior." Ed. M.T. Bianchi. New York : Springer Publishers, 2014. p. 27-32. http://dx.doi.org/10.1007/978-1-4614-9087-6_3 , Jan-2014
Project Title:  Ultra-Short Light Pulses as Efficient Countermeasures for Circadian Misalignment and Objective Performance and Subjective Alertness Decrements Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 08/01/2012  
End Date: 07/31/2015  
Task Last Updated: 08/12/2013 
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: 
Wang, Wei  Brigham and Women's Hospital 
Lockley, Steven  Brigham and Women's Hospital 
Project Information: Grant/Contract No. NCC 9-58-HFP02802 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NCC 9-58-HFP02802 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
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 05:We need to identify environmental specifications and operational regimens for using light to prevent and mitigate health and performance decrements due to sleep, circadian, and neurobehavioral disruption, for flight, surface and ground crews, during all phases of spaceflight operations (IRP Rev E)
Task Description: Lighting protocols have been recognized by NSBRI, NASA, and NIH as important countermeasures for circadian rhythm and sleep disruptions and their associated effects on performance and alertness for both crews in space and workers on Earth. The current light-based countermeasures involve one or more hours of bright light exposure. We have recently demonstrated significant circadian phase shifting with an ultra-short 2-minute bright light stimulus. The use of such a short duration stimulus as a countermeasure would significantly preserve the ability to work in the ISS lighting environment and reduce crew resource requirements. We propose to test the relative efficacy of both ultra-short and longer-duration light protocol countermeasures using the newly approved ISS lighting system to induce both adaptive circadian resetting and direct alerting effects. Experiments will be conducted jointly with Dr. S. Lockley and his NSBRI project. These studies will further our understanding of the physiologic mechanisms that mediate exposure-duration-dependent and wavelength-dependent effects of photic stimuli on circadian phase and performance. Furthermore, results from these experiments will be added to our validated physiologically-based mathematical models of light, sleep/wake and circadian rhythms effects on performance and alertness, including a software application used for determining the optimal timing of light exposure to be employed as a countermeasure for poor performance and alertness as predicted by the other mathematical models. The experimental and modeling results will have direct Earth-based applications for workers on early-rising, night or rotating schedules, as well as for people experiencing jet lag. The proposed work directly addresses one of the NSBRI NRA research objectives and two NASA Human Research Program IRP Risks. This proposal will also address other NSBRI goals: training of future scientists, collaboration among NSBRI investigators, and a combination of basic science with space-based applications and potential commercial applications.

Research Impact/Earth Benefits: Light is the major environmental time cue that resets the circadian pacemaker in the Suprachiasmatic Nucleus (SCN) of the mammalian hypothalamus. Light information is captured exclusively by the eyes using specialized intrinsically photosensitive retinal ganglion cells containing the novel blue-light sensitive photopigment melanopsin and transduced directly to the SCN via a dedicated neural pathway, the retinohypothalamic tract. Each day the light-dark cycle resets the internal clock, which in turn synchronizes the physiology, psychology, and behavior controlled by the clock. Failure to receive this light-dark information, as experienced for example by totally blind individuals, causes the circadian pacemaker to revert to its endogenous non-24-hour period and possibly become desynchronized from the 24-hour light-dark cycle. Exposure to irregular light-dark cycles, as experienced for example by psychiatric patients with irregular sleep-wake cycles, can also disrupt circadian rhythms. In addition to its circadian resetting and melatonin suppression effects, light has a direct arousal effect on the brain, improving alertness and performance. This property of light can be useful as a non-pharmacological treatment for fatigue in a number of conditions, and if timed appropriately, these effects can complement the circadian phase resetting effects of light, for example in treating shiftwork and jet-lag disorders, to help maintain alertness at the correct time and subsequently improve sleep. The results of our experiments in which gradual vs. slam-shift changes in schedule along with continuous or intermittent light exposure are tested for their effects on circadian rhythms, sleep, hormones, subjective alertness, and objective performance will be applicable to conditions such as jet lag, and shift-work or night-work. Millions of workers in the safety, security, transportation, healthcare, and industrial sectors are affected by these conditions yearly, with effects on health and safety. The development of (i) mathematical models of circadian rhythms, sleep, alertness and performance, and (ii) 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, healthcare 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 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 FY2013 
Task Progress: 1) Experimental: We began our recruitment efforts in Jan 2013 and to date we have screened 29 potential participants, 13 participants were excluded based on study inclusion/exclusion criteria, eight participants have completed the study, and an additional seven subjects are completing the screening portion of the study, waiting to start the inpatient phase of the study. One participant was disempaneled from the study. We expect to complete studies in 12 participants by the end of July 2013. Participants are randomized to either the gradual or slam shift arms of the study on the day of admission. The dynamic lighting is generated using the Solid State Lighting Module for Research (SSLM-R), a functional ISS lighting analog that mimics both the geometry of the light sources aboard ISS and the light source and spectra that will eventually be deployed. Primary outcome measures of the study include: a) Circadian phase shifts: Shift in endogenous circadian phase (Dim Light Melatonin Onset; DLMO) between initial and final phase assessment. b) Cognitive performance: Subjective sleepiness measured using the Karolinska Sleepiness Scale. Objective measures of alertness include the visual and auditory psychomotor vigilance tests (PVT) and EEG correlates of alertness. c) Sleep structure and architecture: Polysomnographic assessment of sleep structure and architecture including latency and efficiency.

2) The mathematical model is being updated with the effects of light on the human circadian pacemaker with information from the experimental work and a Division of Sleep Medicine study database. The mathematical model was also used to inform the design of Experiment 1. Using the predictions of the mathematical model, we optimized the timing of the dynamic lighting exposure to maximize circadian phase shifts following an 8-hour advance in the sleep-wake schedule on both the gradual and slam shifts. We have also continued development of the linked circadian, sleep, and performance model to include the effects of chronic sleep restriction and melatonin pharmacokinetics. These additions will greatly improve the utility of the models in real-world conditions, including long duration spaceflights, where chronic sleep restriction is common. The significance of the modeling will be better understanding and prediction of the effects of light on human circadian rhythms, sleep, hormones, performance, and alertness. Progress also addresses other goals within NSBRI: training of future scientists, collaboration between and among NSBRI teams, combination of basic science, space based applications, and other, potentially commercial, applications.

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

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Aeschbach DA, Cohen DA, Czeisler CA, Klerman EB. "Distinct non-additive effects of acute and chronic sleep loss and circadian phase on inadvertent attentional failures." SLEEP 2013—27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A87. Abstract 0237. , May-2013

Abstracts for Journals and Proceedings Buxton OM, Pavlova M, Wang W, Scheer FA, Klerman EB, O'Connor SP, Porter J, McLaren D, Cooper D, Ellenbogen JM. "Examining the Effects of Daytime Eszopiclone Administration on Daytime Sleep and Nighttime Wakefulness: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial in Shift Workers." SLEEP 2013—27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A184-A185. Abstract 0533. , May-2013

Abstracts for Journals and Proceedings Flynn-Evans EE, Barger LK, Kubey A, Wright KP Jr, Klerman EB, Czeisler CA. "Sleep Duration and Medication Use Among Astronauts During Predicted Circadian Misalignment on Long Duration Missions aboard the International Space Station." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2012

Abstracts for Journals and Proceedings Klerman EB, St Hilaire MA, Phillips AJK, Beckett S, Mankowski P, Wang W. "Designing Individual Countermeasures to Reduce Sleep Disruption and Improve Performance and Alertness." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2013

Abstracts for Journals and Proceedings Klerman EB, Wyatt JK, Cohen, DA, Aeschbach D, Gronfier C, Wang W, Czeisler CA. "Effects of Prior Time Awake and Time Asleep on Sleep Structure: Analyses across Forced Desynchrony Protocols with Different Sleep/Wake Cycle Durations." SLEEP 2013—27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A42. Abstract 0107. , May-2013

Abstracts for Journals and Proceedings Klerman EB, Zeitzer JM, Wang W. "Survival-Based Analyses of Monkey Sleep." SLEEP 2013—27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A40-A41. Abstract 0103. , May-2013

Abstracts for Journals and Proceedings Lee ML, Zhang Q, Strangman GE, Klerman EB. "Assessing the Impact of Chronic Sleep Restriction on Sleep and Performance-Associated Regional Brain Activation Using Near Infrared Spectroscopy." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2013

Abstracts for Journals and Proceedings Phillips AJK, Breslow ER, Klerman EB. "Multiple Performance Countermeasures in a Single Modeling Framework." SLEEP 2013—27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A110. Abstract 0307. , May-2013

Abstracts for Journals and Proceedings Phillips AJK, Robinson PA, Klerman EB. "One Homeostat, Two Rebounds: A Parsimonious Hypothetical Mechanism for Wake/Sleep and REM/NREM Sleep Regulation." SLEEP 2013—27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A40. Abstract 0102. , May-2013

Abstracts for Journals and Proceedings Rahman SA, St Hilaire MA, Flynn-Evans EE, Barger LK, Brainard GC, Czeisler CA, Lockley SW. "The ISS Dynamic Lighting Schedule: An In-Flight Lighting Countermeasure to Facilitate Circadian Adaptation, Improve Sleep and Enhance Alertness and Performance on the International Space Station." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2013

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, Klerman EB, Anderson JA. "Modeling the morning light effects of 465nm vs. 595nm suggests a direct alerting mechanism in Seasonal Affective Disorder (SAD) patients." SLEEP 2013—27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A316. Abstract 0924. , May-2013

Abstracts for Journals and Proceedings Wang W, Wyatt JK, Cohen DA, Aeschbach D, Gronfier C, Beckett SA, Mankowski P, Czeisler CA Klerman EB. "Modeling Circadian Influences on Actigraphy Data With Zero-inflated Poisson Distribution." SLEEP 2013—27th Associated Professional Sleep Societies LLC (APSS) Annual Meeting, Baltimore, MD, June 1-5, 2013.

Sleep. 2013;36(Abstract Suppl):A50. Abstract 0131. , May-2013

Articles in Peer-reviewed Journals Breslow ER, Phillips AJ, Huang JM, St Hilaire MA, Klerman EB. "A mathematical model of the circadian phase-shifting effects of exogenous melatonin." J Biol Rhythms. 2013 Feb;28(1):79-89. http://dx.doi.org/10.1177/0748730412468081 ; PubMed PMID: 23382594 , Feb-2013
Articles in Peer-reviewed Journals Gooley JJ, Ho Mien I, St Hilaire MA, Yeo SC, Chua EC, van Reen E, Hanley CJ, Hull JT, Czeisler CA, Lockley SW. "Melanopsin and rod-cone photoreceptors play different roles in mediating pupillary light responses during exposure to continuous light in humans." J Neurosci. 2012 Oct 10;32(41):14242-53. http://dx.doi.org/10.1523/JNEUROSCI.1321-12.2012 ; PubMed PMID: 23055493 , Oct-2012
Articles in Peer-reviewed Journals Phillips AJ, Robinson PA, Klerman EB. "Arousal state feedback as a potential physiological generator of the ultradian REM/NREM sleep cycle." J Theor Biol. 2013 Feb 21;319:75-87. Epub 2012 Dec 5. http://dx.doi.org/10.1016/j.jtbi.2012.11.029 ; PubMed PMID: 23220346 , Feb-2013
Articles in Peer-reviewed Journals Ruger M, St Hilaire MA, Brainard GC, Khalsa SB, Kronauer RE, Czeisler CA, Lockley SW. "Human phase response curve to a single 6.5 h pulse of short-wavelength light." J Physiol. 2013 Jan 1;591(Pt 1):353-63. Epub 2012 Oct 22. http://dx.doi.org/10.1113/jphysiol.2012.239046 ; PubMed PMID: 23090946 , Jan-2013
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." Accident Analysis and Prevention. 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 Breslow E. "John Dowling Prize for Best Thesis in Neurobiology, June 2013." Jun-2013
Awards Breslow E. "Received Honorable Mention and People's Choice Award at the National Collegiate Research Conference, March 2013." Mar-2013
Awards Breslow E. "Summa Cum Laude for thesis, Sensitivity of the Human Circadian Clock to Phase-Resetting Stimuli: Interactions of Melatonin, Light, and Sleep, June 2013." Jun-2013
Awards Klerman E. "Pictured on cover of the BWH Center for Faculty Development and Diversity's Office of Research Career's 2013 Brochure, in recognition of mentoring efforts. May 2013." May-2013
Project Title:  Ultra-Short Light Pulses as Efficient Countermeasures for Circadian Misalignment and Objective Performance and Subjective Alertness Decrements Reduce
Fiscal Year: FY 2012 
Division: Human Research 
Research Discipline/Element:
HRP BHP:Behavioral Health & Performance (archival in 2017)
Start Date: 08/01/2012  
End Date: 07/31/2015  
Task Last Updated: 10/23/2012 
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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: 
Lockley, Steven  Brigham And Women's Hospital, Inc. 
Wang, Wei  Brigham And Women's Hospital, Inc. 
Duda, Kevin  Charles Stark Draper Laboratory Inc. 
Project Information: Grant/Contract No. NCC 9-58-HFP02802 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2011 Crew Health NNJ11ZSA002NA 
Grant/Contract No.: NCC 9-58-HFP02802 
Project Type: GROUND 
Flight Program:  
TechPort: Yes 
No. of Post Docs:  
No. of PhD Candidates:  
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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 05:We need to identify environmental specifications and operational regimens for using light to prevent and mitigate health and performance decrements due to sleep, circadian, and neurobehavioral disruption, for flight, surface and ground crews, during all phases of spaceflight operations (IRP Rev E)
Task Description: Lighting protocols have been recognized by NSBRI, NASA, and NIH as important countermeasures for circadian rhythm and sleep disruptions and their associated effects on performance and alertness for both crews in space and workers on Earth. The current light-based countermeasures involve one or more hours of bright light exposure. We have recently demonstrated significant circadian phase shifting with an ultra-short 2-minute bright light stimulus. The use of such a short duration stimulus as a countermeasure would significantly preserve the ability to work in the ISS lighting environment and reduce crew resource requirements. We propose to test the relative efficacy of both ultra-short and longer-duration light protocol countermeasures using the newly approved ISS lighting system to induce both adaptive circadian resetting and direct alerting effects. The inpatient experiments will involve healthy volunteers whose circadian rhythms and subjective and objective performance and alertness will be studied before, during and after 2-minute or longer exposures to ISS lighting modes. Objective alertness and performance measures will include the Psychomotor Vigilance Task, the Karolinska Drowsiness Test (an EEG-based measure of alertness), Slow Eye Movements (an EOG-based measure of alertness) and lunar lander simulator flight performance, an operational task-specific measure developed by NSBRI investigators. These studies will further our understanding of the physiologic mechanisms that mediate exposure-duration-dependent and wavelength-dependent effects of photic stimuli on circadian phase and performance. Furthermore, results from these experiments will be added to our validated mathematical models: (i) a model of the effects of light on the human circadian pacemaker, (ii) a linked model of effects of circadian phase and length-of-time awake on objective performance and subjective alertness; and (iii) a linked software application used for determining the optimal timing of light exposure to be employed as a countermeasure for poor performance and alertness as predicted by the other two mathematical models. The experimental and modeling results will have direct Earth-based applications for workers on early-rising, night or rotating schedules, as well as for people experiencing jet lag. The proposed work directly addresses one of the NSBRI NRA research objectives and two NASA Human Research Program IRP Risks. This proposal will also address other NSBRI goals: training of future scientists, collaboration among NSBRI investigators, and a combination of basic science with space-based applications and potential commercial applications.

Our specific aims are to (1A) test the phase shifting effect of three different ISS lighting-based protocols compared with a dim light control: (i) continuous General Illumination mode during a 16-hr wake episode; (ii) continuous Phase Shift mode during a 6.5-hr time window centered in a 16-hr wake episode with General Illumination during the rest of the 16-hr wake episode; and (iii) multiple intermittent 2-minute Phase Shift mode exposures within a 6.5-hr time window centered in a 16-hr wake episode with General Illumination during the rest of the 6.5-hr window and during the rest of the 16-hr wake episode; (1B) quantify the relative phase-shifting efficacy of these different lighting conditions; (2) test the melatonin suppression effect of each of the different lighting protocols compared with the dim light control; (3) test the subjective and objective performance and alertness response to each of the different lighting protocols compared with the dim light control; and (4) amend our mathematical model of the effects of light on the human circadian pacemaker and the linked model of the effects of length of time awake and circadian phase on performance and alertness to include the circadian phase-shifting results, the measures from an operationally-relevant task and the direct alerting effects of light.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2012 
Task Progress: New project for FY2012.

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

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 None in FY 2012