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Fiscal Year: FY 2007  Task Last Updated:  10/05/2007 
PI Name: Czeisler, Charles A. 
Project Title: Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral Performance During Extended Duration Space Flight 
   
Division Name: Human Research 
Program/Discipline: NSBRI Teams 
Element/Subdiscipline: Human Performance Factors, Sleep, and Chronobiology Team 
Joint Agency Name:  
Human Research Program Elements: None
Human Research Program Risks:: None
Human Research Program Gaps: None
PI Email: cacadmin@rics.bwh.harvard.edu  Fax:  617-732-4015 
PI Organization Type: UNIVERSITY  Phone: 617-732-4013  
Organization Name: Brigham and Women's Hospital/Harvard Med Ctr 
PI Address 1: Division of Sleep Medicine 
PI Address 2: 221 Longwood Ave., Ste. 438 
PI Web Page:  
City: Boston  State: MA 
Zip Code: 02115-5804  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2003 Biomedical Research & Countermeasures 03-OBPR-04 
Start Date: 03/01/2004  End Date:  04/30/2008 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment: NOTE: Received NCE to 4/30/2008 per K. Major/NSBRI (3/08)

 

Key Personnel Changes/Previous PI:  
COI Name (Institution):  
Grant/Contract No.: NCC 9-58-HPF00402 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: The success of human exploration missions outlined in the goals for the Vision for Space Exploration and in the Global Exploration Strategy and Lunar Architecture announcement will depend on the crew’s ability to remain alert and vigilant while operating sophisticated equipment and following complex procedures. Unfortunately, the space exploration often involves disruptions to planned sleep-wake schedules and/or non-24 hr sleep-wake schedule during these missions. This can impair circadian entrainment to the subsequent sleep-wake cycle which results in sleep impairment, endocrine disturbance, impaired daytime alertness and neurobehavioral function. Our data suggests that most astronauts would exhibit circadian misalignment in the space flight lighting conditions of <25 lux on the windowless middeck of the space shuttle.

Preliminary data from our laboratory reveal that intermittent bright light exposure is effective in maintaining entrainment of the circadian pacemaker to longer-than-24 h days. Other preliminary results demonstrate that blue light (~460 nm wavelength) is more efficient than white light or green light (~ 555 nm wavelength) of equal photon density in resetting the human circadian pacemaker. Given that bright light pulses might not of practical use on the lunar or Martian habitats — due to time and energy constraints — these results demonstrate the need to develop practical and cost-effective countermeasures for addressing the challenges to the human circadian pacemaker during space missions.

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

Seven healthy subjects participated in a 71-day inpatient protocol consisting of 3 baseline days (16:8 h wake:sleep) followed by 60 experimental days (24.65 h, 16.43:8.22 h). Light intensity during the experimental days was ~ 100 lux (n=2) and ~50 lux (n = 5) at 137 cm height in the horizontal angle. Circadian phase was measured by the Dim Light Melatonin Onset (DLMO) measured 6 times under dim light (~ 1.8 lux at 137 cm height in the horizontal angle ) and postural control (before and after the experimental days, and on experimental Days 6, 20, 34, & 48) and during several segments on the experimental days. The critical manipulation in the study was the timing of sleep on the first experimental day was shifted 12 h compared to baseline; equivalent to a slam shift. To assess entrainment, phase angle was calculated from the difference between DLMO and scheduled bedtime. The results showed that the average phase angle for subjects on the first 24.65h day was 12.5 + .26 hours for the 50 lux group and 8.96 + .96 hours for the 100 lux group, which is indicative of acute circadian misalignment. The average phase angle on the 6th experimental day was 5.8 + 1.6h for the 50 lux group and 7 + 3.7 h for the 100 lux group, showing that subjects continued to be misaligned. The average phase angle on the 15th experimental day was 1.5 + .46. Thereafter they stabilized. The average phase angle was 2.4 + .31h on experimental day 34 and 2.2 + .26h on experimental day 48 (p>.05). The analysis of the cognitive data under these conditions is ongoing.

It is important to note the following: First, our results showed that crew members would be most vulnerable to the detrimental effects of circadian misalignment during the first two weeks of a mission. This is important, because the duration of short-term mission such as those to the ISS and the moon are approximately two weeks long. Second, the data reveal that light intensities that are similar to the lighting conditions during space flight are insufficient to induce rapid entrainment during a short-term mission. Therefore, we concluded that it was critical to develop countermeasures that would facilitate sleep and circadian adaptation rapidly.

We refocused our research efforts on the circadian and sleep-wake challenges associated with short duration lunar exploration. To do so, we modified our studies during the remainder of this grant period to explore this initial period of vulnerability further and test the effectiveness of our proposed countermeasure (blue enriched light) in short term missions. The progress toward developing the blue light countermeasures is moving forward with the continuing work on the modified 12-day protocol. We have completed 6 subjects in the protocol, have 2 subjects currently in the laboratory and several subjects who are being screened into the protocol.

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

 

Research Impact/Earth Benefits: Since the finding that appropriately scheduled light/dark exposure is a powerful means of resetting the human circadian pacemaker, bright light has been used in various clinical settings to induce physiologic adaptation in individuals suffering from circadian rhythm disorders (e.g. night shift workers, people with Advanced and Delayed Sleep Phase Syndromes). We have found that appropriately timed exposure to bright light can produce rapid physiologic adaptation of the circadian pacemaker to a single week of night work and facilitate rapid entrainment to a rotating work schedule, as well as enhance the alertness of night workers during their work shifts. Advanced and Delayed Sleep Phase Syndromes (ASPS and DSPS, respectively) are characterized by a marked difficulty in maintaining appropriate timing of sleep during the desired hours, and there is evidence suggesting that circadian misalignment may underlie the pathophysiology of this condition. We and others have reported data from clinical studies which suggest that evening exposure to bright light or early morning exposure to bright light are successful in the treatment of Advanced Sleep Phase Syndrome or Delayed Sleep Phase Syndrome, respectively. Since the current study is designed to evaluate the effectiveness of blue-enriched light exposure over white light as a countermeasure for circadian misalignment during exploration class mission to mars, it has implications for the development of effective and energy-efficient methods for treatment of circadian rhythm disorders. Optimizing the wavelength of light holds the potential for producing shorter, more efficient light treatment regimens. Shorter treatment regimens would not only increase compliance in clinical populations, but would make light treatment more practical in industrial/work settings.

 

Task Progress: In our current NSBRI project, we initially proposed to test a countermeasure of "blue-enriched" light to entrain the human circadian pacemaker to the 24.65-h Martian day. As of this past year seven healthy subjects have successfully completed the 71-day inpatient protocol. Our results showed that crew members would be most vulnerable to the detrimental effects of circadian misalignment during the first two weeks of a mission. This is important, because the duration of short-term mission such as those to the ISS and the moon are approximately two weeks long. Moreover, the data reveal that light intensities that are similar to the lighting conditions during space flight are insufficient to induce rapid entrainment during a short-term mission. Based on these results, we felt that it was critical to develop countermeasures that would facilitate sleep and circadian adaptation rapidly. To do so, we modified our protocol from 71 to 12 days to explore this initial period of vulnerability further and specifically test the effectiveness of our proposed countermeasure (blue enriched light) to hasten circadian adaptation to short term missions and thereby improve sleep during scheduled sleep episodes and improve performance during scheduled wake episodes. The progress toward developing the blue light countermeasures is moving forward with the continuing work on the modified 12-day protocol. We have completed 6 subjects in the protocol, have 2 subjects currently in the laboratory and several subjects who are being screened into the protocol. In the coming year we plan to complete the project and complete the analysis of the physiological and neurobehavioral data.

 

Bibliography Type: Description: (Last Updated: 06/29/2010) Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Ayas NT, Barger LK, Cade BE, Hashimoto DM, Rosner B, Cronin JW, Speizer FE, Czeisler CA. "Extended work duration and the risk of self-reported percutaneous injuries in interns." JAMA. 2006 Sep 6;296(9):1055-62. PMID: 16954484 , Sep-2006
Articles in Peer-reviewed Journals Lockley SW, Landrigan CP, Barger LK, Czeisler CA; Harvard Work Hours Health and Safety Group. "When policy meets physiology: the challenge of reducing resident work hours." Clin Orthop Relat Res. 2006 Aug;449:116-27. Review. PMID: 16770285 , Aug-2006
Articles in Peer-reviewed Journals Wright KP Jr, Hull JT, Hughes RJ, Ronda JM, Czeisler CA. "Sleep and wakefulness out of phase with internal biological time impairs learning in humans." J Cogn Neurosci. 2006 Apr;18(4):508-21. PMID: 16768357 , Mar-2006
Articles in Peer-reviewed Journals Wertz AT, Ronda JM, Czeisler CA, Wright KP Jr. "Effects of sleep inertia on cognition." JAMA. 2006 Jan 11;295(2):163-4. Erratum in: JAMA. 2006 Feb 15;295(7):760. PMID: 16403927 , Jan-2006
Awards Czeisler CA. "10th Annual J.Gerald Reves Duke Heart Center Lecture, Duke Medical Center, NC. February 2007." Feb-2007
Awards Czeisler CA. "National Sleep Foundation, 2006 Healthy Sleep Community Award (Harvard Work Hours and Health and Safety Group). February 2006." Feb-2006
Awards Czeisler CA. "NIOSH Director's Award for Scientific Leadership in Occupational Safety And Health. January 2005." Jan-2005
 
Fiscal Year: FY 2006  Task Last Updated:  01/08/2007 
PI Name: Czeisler, Charles A. 
Project Title: Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral Performance During Extended Duration Space Flight 
   
Division Name: Human Research 
Program/Discipline: NSBRI Teams 
Element/Subdiscipline: Human Performance Factors, Sleep, and Chronobiology Team 
Joint Agency Name:  
Human Research Program Elements: None
Human Research Program Risks:: None
Human Research Program Gaps: None
PI Email: cacadmin@rics.bwh.harvard.edu  Fax:  617-732-4015 
PI Organization Type: UNIVERSITY  Phone: 617-732-4013  
Organization Name: Brigham and Women's Hospital/Harvard Med Ctr 
PI Address 1: Division of Sleep Medicine 
PI Address 2: 221 Longwood Ave., Ste. 438 
PI Web Page:  
City: Boston  State: MA 
Zip Code: 02115-5804  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2003 Biomedical Research & Countermeasures 03-OBPR-04 
Start Date: 03/01/2004  End Date:  02/29/2008 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution):  
Grant/Contract No.: NCC 9-58-HPF00402 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: NASA's planned exploration class mission to Mars will require crewmembers to adapt to a 24.65-h solar day throughout their >540 day stay on Mars. The ability of astronauts to sustain a high level of performance during their mission will be critically dependent upon adaptation of their circadian pacemaker to the 24.65-h day. Our data suggest that most astronauts would exhibit circadian misalignment if the space flight lighting conditions of <25 lux on the windowless middeck of the space shuttle were present during their stay on Mars. Circadian misalignment would result in sleep impairment, endocrine disturbances, and impaired neurobehavioral function. Preliminary data from our laboratory reveal that intermittent bright light exposure is effective in maintaining entrainment of the circadian pacemaker to longer-than-24 h days. They also suggest that lighting levels of ~25 lux - ~100 lux are insufficient to maintain a normal phase angle of entrainment. Other preliminary results demonstrate that blue light (460 nm) is more efficient than white light in resetting the human circadian pacemaker. Given that bright light pulses might not of practical use on Mars—due to time and energy constraints—these results demonstrate the need to develop practical and cost-effective countermeasures to adapt the human circadian pacemaker of all crewmembers to the 24.65-h day.

In the current grant we proposed to test a countermeasure of "blue-enriched" light to entrain the human circadian pacemaker to a 24.65-h day. Specifically, we proposed to test the following hypotheses: i) that synchronization of the human circadian pacemaker to a 24.65-h day initiated at an adverse phase will not be appropriate in the presence of ~100 lux of white light; ii) that inappropriate circadian synchronization will result in the secretion of the sleep-promoting hormone melatonin during waketime, abnormal somatotropic and corticotropic activity, disturbed sleep, and impaired performance and daytime alertness; and iii) that exposure to "blue enriched" light during the daytime will establish a normal entrained circadian phase in subjects scheduled to a 24.65-h day.

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

The results showed that the average phase angle for subjects on the first 24.65h day was 12.5 + .26 hours for the 50 lux group and 8.96 + .96 hours for the 100 lux group, which is indicative of acute circadian misalignment. The average phase angle on the 6th experimental day was 5.8 + 1.6h for the 50 lux group and 7 + 3.7 h for the 100 lux group, showing that subjects continued to be misaligned. The average phase angle on the 15th experimental day was 1.5 + .46. Thereafter they stabilized. The average phase angle was 2.4 + .31h on experimental day 34 and 2.2 + .26h on experimental day 48 (p>.05). The analysis of the cognitive performance data under these conditions is ongoing.

It is important to note the following about these results. First, our results show that crew members would be most vulnerable to the detrimental effects of circadian misalignment during the first two weeks of a mission. This is important, because the duration of short-term mission such as those to the ISS and the moon are approximately two weeks long. Second, the data reveal that light intensities that are similar to the lighting conditions during space flight are insufficient to induce rapid entrainment during a short term mission. Therefore, we feel that it is critical to develop countermeasures that would facilitate sleep and circadian adaptation rapidly. Based on our current results and based on the Vision for Space exploration outlined by President Bush, we feel that it is important to refocus our research efforts on the circadian and sleep-wake challenges associated with short duration lunar exploration. To do so, we plan to modify our studies during the remainder of this grant period to explore this initial period of vulnerability further and specifically test the effectiveness of our proposed countermeasure (blue enriched light) to hasten circadian adaptation to short term missions and thereby improve sleep during scheduled sleep episodes and improve performance during scheduled wake episodes.

The results of the proposed studies will answer fundamental questions on the mechanisms underlying circadian entrainment in humans and could have a profound effect on the health, productivity and safety of astronauts during space exploration missions.The current project, aimed at evaluating the effectiveness of blue-enriched light exposure over white light as a countermeasure for circadian misalignment during planned missions to the ISS, Moon and further destinations (as outlined in the Vision for Space exploration)using the proposed Crew Exploration Vehicle (CEV) will help us address these key issues.

 

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

 

Task Progress: In the current grant we proposed to test a countermeasure of "blue-enriched" light to entrain the human circadian pacemaker to a 24.65-h day.

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

We have so far analyzed the plasma melatonin data. To assess entrainment, phase angle was calculated from the difference between DLMO and scheduled bedtime. The results showed that the average phase angle for subjects on the first 24.65h day was 12.5 + .26 hours for the 50 lux group and 8.96 + .96 hours for the 100 lux group, which is indicative of acute circadian misalignment. The average phase angle on the 6th experimental day was 5.8 + 1.6h for the 50 lux group and 7 + 3.7 h for the 100 lux group, showing that subjects continued to be misaligned. The average phase angle on the 15th experimental day was 1.5 + .46. Thereafter they stabilized. The average phase angle was 2.4 + .31h on experimental day 34 and 2.2 + .26h on experimental day 48 (p>.05). The Analysis of the cognitive performance data under these conditions is ongoing.

It is important to note the following about these results. First, our results show that crew members would be most vulnerable to the detrimental effects of circadian misalignment during the first two weeks of a mission. This is important, because the duration of short-term mission such as those to the ISS and the moon are approximately two weeks long. Second, the data reveal that light intensities that are similar to the lighting conditions during space flight are insufficient to induce rapid entrainment during a short term mission. Therefore, we feel that it is critical to develop countermeasures that would facilitate sleep and circadian adaptation rapidly.

 

Bibliography Type: Description: (Last Updated: 06/29/2010) Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Frey DJ, Badia P, Wright K P Jr. "Relationships among neurobehavioral performance measures during two nights of sleep deprivation." Associated Professional Sleep Societies 17th Annual Meeting, Chicago, Illinois, June 3-8, 2003.

Sleep. 2003;26:A197. , Jun-2003

Abstracts for Journals and Proceedings Umali M, Ronda J M, Czeisler C A, Wright K P Jr. "Sleep EEG measure of slow wave activity during the first five recovery nights." Associated Professional Sleep Societies 17th Annual Meeting, Chicago, Illinois, June 3-8, 2003.

Sleep. 2003;26:A188. , Jun-2003

Abstracts for Journals and Proceedings Wright K P Jr, Hull J T, Hughes R J, Ronda J M, Czeisler C A. "Chronic sleep loss and circadain misalignment impairs learning." Associated Professional Sleep Societies 17th Annual Meeting, Chicago, Illinois, June 3-8, 2003.

Sleep. 2003;26:A199. , Jun-2003

Articles in Peer-reviewed Journals Barger LK, Cade BE, Ayas NT, Cronin JW, Rosner B, Speizer FE, Czeisler CA; Harvard Work Hours, Health, and Safety Group. "Extended work shifts and the risk of motor vehicle crashes among interns." N Engl J Med. 2005 Jan 13;352(2):125-34. PMID: 15647575 , Jan-2005
Articles in Peer-reviewed Journals Barger LK, Wright KP Jr, Hughes RJ, Czeisler CA. "Daily exercise facilitates phase delays of circadian melatonin rhythm in very dim light." Am J Physiol Regul Integr Comp Physiol. 2004 Jun;286(6):R1077-84. PMID: 15031136 , Jun-2004
Articles in Peer-reviewed Journals Czeisler CA, Walsh JK, Roth T, Hughes RJ, Wright KP, Kingsbury L, Arora S, Schwartz JR, Niebler GE, Dinges DF; U.S. Modafinil in Shift Work Sleep Disorder Study Group. "Modafinil for excessive sleepiness associated with shift-work sleep disorder." N Engl J Med. 2005 Aug 4;353(5):476-86. Erratum in: N Engl J Med. 2005 Sep 8;353(10):1078. PMID: 16079371 , Aug-2005
Articles in Peer-reviewed Journals Hull JT, Wright KP Jr, Czeisler CA. "The influence of subjective alertness and motivation on human performance independent of circadian and homeostatic regulation." J Biol Rhythms. 2003 Aug;18(4):329-38. PMID: 12932085 , Aug-2003
Articles in Peer-reviewed Journals Lockley SW, Evans EE, Scheer FA, Brainard GC, Czeisler CA, Aeschbach D. "Short-wavelength sensitivity for the direct effects of light on alertness, vigilance and waking electroencephalogram in humans." Sleep. 2006 Feb 1;29(2):161-8. PMID: 16494083 , Feb-2006
Articles in Peer-reviewed Journals Wright KP Jr, Gronfier C, Duffy JF, Czeisler CA. "Intrinsic period and light intensity determine the phase relationship between melatonin and sleep in humans." J Biol Rhythms. 2005 Apr;20(2):168-77. PMID: 15834113 , Apr-2005
Articles in Peer-reviewed Journals Wyatt JK, Cajochen C, Ritz-De Cecco A, Czeisler CA, Dijk DJ. "Low-dose repeated caffeine administration for circadian-phase-dependent performance degradation during extended wakefulness." Sleep. 2004 May 1;27(3):374-81. PMID: 15164887 , May-2004
Awards "National Sleep Foundation's 2006 Healthy Sleep Community Award." Jan-2006
Awards "NIOSH Director's Award for Scientific Leadership in Occupational Safety and Health." Jan-2006
 
Fiscal Year: FY 2005  Task Last Updated:  10/21/2005 
PI Name: Czeisler, Charles A. 
Project Title: Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral Performance During Extended Duration Space Flight 
   
Division Name: Human Research 
Program/Discipline: NSBRI Teams 
Element/Subdiscipline: Human Performance Factors, Sleep, and Chronobiology Team 
Joint Agency Name:  
Human Research Program Elements: None
Human Research Program Risks:: None
Human Research Program Gaps: None
PI Email: cacadmin@rics.bwh.harvard.edu  Fax:  617-732-4015 
PI Organization Type: UNIVERSITY  Phone: 617-732-4013  
Organization Name: Brigham and Women's Hospital/Harvard Med Ctr 
PI Address 1: Division of Sleep Medicine 
PI Address 2: 221 Longwood Ave., Ste. 438 
PI Web Page:  
City: Boston  State: MA 
Zip Code: 02115-5804  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2003 Biomedical Research & Countermeasures 03-OBPR-04 
Start Date: 03/01/2004  End Date:  02/29/2008 
No. of Post Docs: No. of PhD Degrees: 
No. of PhD Candidates: No. of Master' Degrees: 
No. of Master's Candidates: No. of Bachelor's Degrees: 
No. of Bachelor's Candidates: Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution):  
Grant/Contract No.: NCC 9-58-HPF00402 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: NASA's planned exploration class mission to Mars will require crewmembers to adapt to a 24.65-h solar day throughout their >540 day stay on Mars. The ability of astronauts to sustain a high level of performance during their mission will be critically dependent upon adaptation of their circadian pacemaker to the 24.65-h day. Our data suggest that most astronauts would exhibit circadian misalignment if the space flight lighting conditions of <25 lux on the windowless middeck of the space shuttle were present during their stay on Mars. Circadian misalignment would result in sleep impairment, endocrine disturbances, and impaired neurobehavioral function. Preliminary data from our laboratory reveal that intermittent bright light exposure is effective in maintaining entrainment of the circadian pacemaker to longer-than-24 h days. They also suggest that lighting levels of ~25 lux or ~100 lux are insufficient to maintain a normal phase angle of entrainment. Other preliminary results demonstrate that blue light (460 nm) is more efficient than white light in resetting the human circadian pacemaker. Given that bright light pulses might not of practical use on Mars—due to time and energy constraints—these results demonstrate the need to develop practical and cost-effective countermeasures to adapt the human circadian pacemaker of all crewmembers to the 24.65-h day. We propose to test a countermeasure of "blue-enriched" light to entrain the human circadian pacemaker to a 24.65-h day. Specifically, we propose to test the following hypotheses: i) that synchronization of the human circadian pacemaker to a 24.65-h day initiated at an adverse phase will not be appropriate in the presence of ~100 lux of white light; ii) that inappropriate circadian synchronization will result in the secretion of the sleep-promoting hormone melatonin during waketime, abnormal somatotropic and corticotropic activity, disturbed sleep, and impaired performance and daytime alertness; and iii) that exposure to "blue enriched" light during the daytime will establish a normal entrained circadian phase in subjects scheduled to a 24.65-h day. We have proposed a randomized 71-day clinical trial to test these three hypotheses. The results of the proposed studies will answer fundamental questions on the mechanisms underlying circadian entrainment in humans and could have a profound effect on the health, productivity and safety of astronauts during an exploration class mission to Mars.

 

Research Impact/Earth Benefits: The purpose of the proposed studies is to test three specific hypotheses aimed at evaluating the effectiveness of blue-enriched light exposure over white light as a countermeasure for circadian misalignment during exploration class mission to mars. Results from previous studies in our lab indicate exposure to blue-enriched light will be a more effective means of entraining the human circadian pacemaker compared to exposure to white light of similar photon density, or even to light of greater photon density but of inappropriate spectral content (long wavelengths, as on Mars). The funded research project has important implications for earth-based applications, particularly in the development of treatment for circadian rhythm disorders. Since the finding that appropriately scheduled light/dark exposure is a powerful means of resetting the human circadian pacemaker, bright light has been used in various clinical settings to induce physiologic adaptation in individuals suffering from circadian rhythm disorders (e.g. night shift workers, people with Advanced and Delayed Sleep Phase Syndromes). Misalignment of circadian phase and work-sleep schedules can overpower the night-shift worker's ability to remain awake and attentive while at work leading to impaired job performance and higher rates of accidents and injuries. We have found that appropriately timed exposure to bright light can produce rapid physiologic adaptation of the circadian pacemaker to a single week of night work and facilitate rapid entrainment to a rotating work schedule, as well as enhance the alertness of night workers during their work shifts. Advanced and Delayed Sleep Phase Syndromes (ASPS and DSPS, respectively) are characterized by a marked difficulty in maintaining appropriate timing of sleep during the desired hours, and there is evidence suggesting that circadian misalignment may underlie the pathophysiology of this condition. We and others have reported data from clinical studies which suggest that evening exposure to bright light or early morning exposure to bright light are successful in the treatment of Advanced Sleep Phase Syndrome or Delayed Sleep Phase Syndrome, respectively. Since the current study is designed to evaluate the effectiveness of blue-enriched light exposure over white light as a countermeasure for circadian misalignment during exploration class mission to mars, it has implications for the development of effective and energy-efficient methods for treatment of circadian rhythm disorders. Optimizing the wavelength of light holds the potential for producing shorter, more efficient light treatment regimens. Shorter treatment regimens would not only increase compliance in clinical populations, but would make light treatment more practical in industrial/work settings.

 

Task Progress: We have completed two subjects in the proposed 71-Day protocol, one over the last funded year and one this year. A third subject is being studied currently. Two more subjects are scheduled to start the study in June-july. Data collected in the two studies include: Core body temperature, blood samples (melatonin, cortisol, IGF-1), Sleep and waking EEG recordings, Subjective sleep quality, Actigraphy, Light intensity, neurobehavioral performance and mood. The successful collection of these data will allow us to test hypotheses 1, 2, and 3 of the project. Analyses of the collected data are currently in progress.

 

Bibliography Type: Description: (Last Updated: 06/29/2010) Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Hull JT, Wright KP Jr, Czeisler CA. "The influence of subjective alertness and motivation on human performance independent of circadian and homeostatic regulation." J Biol Rhythms. 2003 Aug;18(4):329-38. PMID: 12932085 , Jan-2004
Articles in Peer-reviewed Journals Wright Jr, K. P., Gronfier, C, Duffy, J. F., Czeisler, C. A. "Intrinsic circadian period and strength of the circadian synchronizer determines the phase relationship between melatonin onset, habitual sleep time and light-dark cycles in humans." N/A , Jan-2004
Articles in Peer-reviewed Journals Wright KP Jr, Gronfier C, Duffy JF, Czeisler CA. "Intrinsic period and light intensity determine the phase relationship between melatonin and sleep in humans." J Biol Rhythms. 2005 Apr;20(2):168-77. PMID: 15834113 , Apr-2005
Presentation Gronfier, C "Entrainment of the human circadian timing system to a longer-than-24-h sleep-wake cycle" N/A

Jun-2004

Presentation Gronfier, C "Entrainment of the human circadian timing system to a longer-than-24-h sleep-wake cycle." N/A

May-2004

Presentation Gronfier, C "Use of intermittent bright light for entrainment of the human circadian pacemaker." N/A

Jul-2004

Presentation Gronfier, C. "Circadian entrainment, sleep-wake regulation and neurobehavioral performance during space flight" N/A

Jan-2004

Presentation Wright, K. P. Jr. "Control of Waking Functions by Homeostatic and Circadian Processes." N/A

Jun-2004

Presentation Wright, K. P. Jr. "Entrainment of the Human Biological Clock" N/A

Feb-2004

Presentation Wright, K. P. Jr. "Photic entrainment of the human circadian timing system to the day length of Mars" N/A

Jul-2004

Presentation Wright, K. P. Jr. "Principles of Circadian Entrainment in Humans" N/A

May-2004

 
Fiscal Year: FY 2004  Task Last Updated:  03/23/2006 
PI Name: Czeisler, Charles A. 
Project Title: Circadian Entrainment, Sleep-Wake Regulation and Neurobehavioral Performance During Extended Duration Space Flight 
   
Division Name: Human Research 
Program/Discipline: NSBRI Teams 
Element/Subdiscipline: Human Performance Factors, Sleep, and Chronobiology Team 
Joint Agency Name:  
Human Research Program Elements: None
Human Research Program Risks:: None
Human Research Program Gaps: None
PI Email: cacadmin@rics.bwh.harvard.edu  Fax:  617-732-4015 
PI Organization Type: UNIVERSITY  Phone: 617-732-4013  
Organization Name: Brigham and Women's Hospital/Harvard Med Ctr 
PI Address 1: Division of Sleep Medicine 
PI Address 2: 221 Longwood Ave., Ste. 438 
PI Web Page:  
City: Boston  State: MA 
Zip Code: 02115-5804  Congressional District: 
Comments:  
Project Type: GROUND  Solicitation:  2003 Biomedical Research & Countermeasures 03-OBPR-04 
Start Date: 03/01/2004  End Date:  02/29/2008 
No. of Post Docs:   No. of PhD Degrees:   
No. of PhD Candidates:   No. of Master' Degrees:   
No. of Master's Candidates:   No. of Bachelor's Degrees:   
No. of Bachelor's Candidates:   Monitoring Center:  NSBRI 
Contact Monitor:   Contact Phone:   
Contact Email:  
Flight Program:  
Flight Assignment:

 

Key Personnel Changes/Previous PI:  
COI Name (Institution):  
Grant/Contract No.: NCC 9-58-HPF00402 
Performance Goal No.:  
Performance Goal Text:

 

Task Description: NASA's planned exploration class mission to Mars will require crewmembers to adapt to a 24.65-h solar day throughout their >540 day stay on Mars. The ability of astronauts to sustain a high level of performance during their mission will be critically dependent upon adaptation of their circadian pacemaker to the 24.65-h day. Our data suggest that most astronauts would exhibit circadian misalignment if the space flight lighting conditions of <25 lux on the windowless middeck of the space shuttle were present during their stay on Mars. Circadian misalignment would result in sleep impairment, endocrine disturbances, and impaired neurobehavioral function. Preliminary data from our laboratory reveal that intermittent bright light exposure is effective in maintaining entrainment of the circadian pacemaker to longer-than-24 h days. They also suggest that lighting levels of ~25 lux or ~100 lux are insufficient to maintain a normal phase angle of entrainment. Other preliminary results demonstrate that blue light (460 nm) is more efficient than white light in resetting the human circadian pacemaker. Given that bright light pulses might not of practical use on Mars—due to time and energy constraints—these results demonstrate the need to develop practical and cost-effective countermeasures to adapt the human circadian pacemaker of all crewmembers to the 24.65-h day. We propose to test a countermeasure of "blue-enriched" light to entrain the human circadian pacemaker to a 24.65-h day. Specifically, we propose to test the following hypotheses: i) that synchronization of the human circadian pacemaker to a 24.65-h day initiated at an adverse phase will not be appropriate in the presence of ~100 lux of white light; ii) that inappropriate circadian synchronization will result in the secretion of the sleep-promoting hormone melatonin during waketime, abnormal somatotropic and corticotropic activity, disturbed sleep, and impaired performance and daytime alertness; and iii) that exposure to "blue enriched" light during the daytime will establish a normal entrained circadian phase in subjects scheduled to a 24.65-h day. We have proposed a randomized 71-day clinical trial to test these three hypotheses. The results of the proposed studies will answer fundamental questions on the mechanisms underlying circadian entrainment in humans and could have a profound effect on the health, productivity and safety of astronauts during an exploration class mission to Mars.

 

Research Impact/Earth Benefits:

 

Task Progress: No progress report this reporting period.

 

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