Millions of Americans routinely sleep less than six hours per night, an amount shown to be insufficient for maintaining healthy physiologic function, with documented abnormalities in metabolism, immune function, hormones, mood and performance/alertness. The cumulative cost of chronic sleep deficiency predisposes an individual to attentional lapses, errors, and accidents. The effect of sleep deficiency on performance is pronounced during the biological (circadian) night, particularly when circadian rhythms are not synchronized to the sleep-wake schedule, as may occur in the 15 percent of Americans who are involved in shift work. We recently demonstrated that sleep restriction affects at least two different regulatory processes in the brain that act on different time scales o affect performance. A short-term process builds over hours and can be rapidly recovered within one long sleep episode. A long-term process builds over days-to-weeks of restricted sleep and has a longer time course of recovery. Key unknown information, however, for determining appropriate counter-measures or public health education, is how the finite durations of recent sleep and wake episodes and the overall sleep:wake ratio affect the short-term and long-term consequences of sleep deficiency. The results of the proposed work will allow us to determine the dynamics of the short- and long-term consequences of chronic sleep restriction (CSR) and how they combine with circadian timing to determine performance at any given time. Participants will live on a recurring 20-hr sleep+wake schedule for three weeks to uncouple the sleep-wake cycles from the intrinsic near-24 hour rhythm of alertness and performance. The CSR group will experience the equivalent of 5.6 hrs sleep per 24 hrs (1:3.3 sleep:wake ratio) while a control group will experience a standard "habitual" 1:2 sleep:wake ratio. These data will be statistically compared with already collected data from experiments in the same facility with CSR (1:3.3 sleep:wake) and standard (1:2 sleep:wake) sleep:wake ratios but different absolute sleep and wake durations under 28-hour and 42.85-hr sleep+wake cycle durations. Full understanding of sleep homeostasis requires experimental manipulation of both sleep:wake ratio and durations of sleep and wake, as well as the interaction with circadian phase. There is immediate

Public Health Relevance

to this work. The proposed research will contribute to the understanding of the short-term and long-term consequences of sleep deficiency on performance and how these effects of sleep deficiency are influenced by the natural ~24-hour rhythm of the internal body clock. It is important to understand how sleep restriction and circadian timing interact to determine performance so that (i) work shift regulations can be developed to minimize the chances for fatigue-related industrial accidents and motor vehicle crashes and (ii) individuals can responsibly plan their sleep. This work will also advance research methods that can be used to test the effectiveness of wake-promoting therapeutics and other interventions on these two distinct processes involved in sleep-wake regulation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL114088-03
Application #
8680363
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Twery, Michael
Project Start
2012-05-01
Project End
2016-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
$729,856
Indirect Cost
$320,973
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Klerman, Elizabeth B; Beckett, Scott A; Landrigan, Christopher P (2016) Applying mathematical models to predict resident physician performance and alertness on traditional and novel work schedules. BMC Med Educ 16:239
Shaw, Natalie D; McHill, Andrew W; Schiavon, Michele et al. (2016) Effect of Slow Wave Sleep Disruption on Metabolic Parameters in Adolescents. Sleep 39:1591-9
Bermudez, Eduardo B; Klerman, Elizabeth B; Czeisler, Charles A et al. (2016) Prediction of Vigilant Attention and Cognitive Performance Using Self-Reported Alertness, Circadian Phase, Hours since Awakening, and Accumulated Sleep Loss. PLoS One 11:e0151770
Lane, Jacqueline M; Chang, Anne-Marie; Bjonnes, Andrew C et al. (2016) Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology. Diabetes 65:1741-51
Sano, Akane; Yu, Amy Z; McHill, Andrew W et al. (2015) Prediction of Happy-Sad mood from daily behaviors and previous sleep history. Conf Proc IEEE Eng Med Biol Soc 2015:6796-9
Faghih, Rose T; Dahleh, Munther A; Adler, Gail K et al. (2015) Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing. IEEE Trans Biomed Eng 62:2379-88
Vijayan, Sujith; Klerman, Elizabeth B; Adler, Gail K et al. (2015) Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia. J Neurophysiol 114:1923-30
Balasubramanian, Ravikumar; Cohen, Daniel A; Klerman, Elizabeth B et al. (2014) Absence of central circadian pacemaker abnormalities in humans with loss of function mutation in prokineticin 2. J Clin Endocrinol Metab 99:E561-6
Faghih, Rose T; Dahleh, Munther A; Adler, Gail K et al. (2014) Deconvolution of serum cortisol levels by using compressed sensing. PLoS One 9:e85204
Dean 2nd, Dennis A; Adler, Gail K; Nguyen, David P et al. (2014) Biological time series analysis using a context free language: applicability to pulsatile hormone data. PLoS One 9:e104087

Showing the most recent 10 out of 16 publications