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Principal Investigator:
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Elizabeth B. Klerman, M.D., Ph.D.
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Organization:
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Harvard-Brigham and Women's Hospital
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Project Ended:
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2012
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During missions on the ground and in space, sleep patterns are often disrupted by mission-related work schedules for astronauts and ground support personnel, increasing the risk to crew safety and to mission success. Performance and alertness are strongly influenced by internal circadian rhythms, which are approximately 24 hours, and length of time awake. As a result, performance and alertness are often adversely affected by these schedules. Therefore, it is imperative that schedules and countermeasures be designed to optimize individual performance, alertness and sleep quality.
Dr. Elizabeth B. Klerman and colleagues are developing prediction and countermeasure design strategies through the use of mathematical models. The project goals include updating modeling software to provide specific data and reports, including wrist-worn activity and light monitor data as input, and tailoring the design of countermeasures for each individual's circadian and sleep characteristics.
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Principal Investigator:
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Elizabeth B. Klerman, M.D., Ph.D.
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Organization:
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Harvard-Brigham and Women's Hospital
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Project Ended:
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2012
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Objective neurobehavioral performance, subjective alertness and sleep are critically important to astronaut and ground-based crew health and to ensure the success of space missions. Neurobehavioral performance and alertness are affected by changes in circadian rhythms, homeostatic sleep/wake regulation and sleep inertia, and the interactions of these processes. During space missions, circadian rhythms and sleep are disrupted, both for astronauts and ground-based crew. Problems with sleep, circadian rhythms and performance have been reported in astronauts, and NASA data indicate that sleeping pills are among the most commonly used drugs in space. Therefore, it is imperative that work and sleep/wake schedules, including the timing of countermeasures such as light, are designed to optimize individual performance, alertness, and sleep quality relative to operational requirements. Our approach to designing countermeasures is to develop new scheduling techniques and software that use mathematical models to describe the underlying physiology of internal timing, performance and sleep.
We have developed and validated two linked mathematical models: one of the human circadian pacemaker that includes the influence of light and of non-photic processes, and one of performance and alertness that includes the key processes of circadian rhythms, sleep/wake homeostasis and sleep inertia. Together, these models are able to predict the effects of sleep/wake, sleep inertia and circadian phase on performance and alertness. Each performance or alertness measure has a separate equation, reflecting the underlying physiological processes in the effect of sleep/wake on performance and alertness. Circadian Performance Simulation Software (CPSS), the software implementing this model, has been used by NASA and consultants when designing light countermeasures for astronaut pre-launch schedules as well as for designing in-flight schedules. To further improve this mathematical model and this method for optimal design of countermeasures, our modeling work will focus on individual, rather than group, predictions and use novel non-linear mathematical and statistical methods. These projects address NASA’s objectives to improve the design of individual countermeasures to reduce sleep disruption and improve performance and alertness in space and on Earth.
Current Progress
We developed a novel scheduling algorithm called Shifter that automatically designs optimal light countermeasures for user-defined NASA-related schedules. Light interventions have been demonstrated to minimize fatigue, improve performance, and improve sleep in experimental and field studies. Shifter allows individuals who are not circadian experts to design schedules and light interventions within minutes. Previous design of light interventions, such as for the 24.65-hr Mars Day experimental protocol (NASA and NSBRI supported, Dr. Charles Czeisler, PI), took approximately two weeks. The scheduling framework can be applied to non-NASA-related work schedules including shift-work and transmeridian travel. We are currently applying our methods to the design of schedules for medical residents, so as to provide schedules that predict optimal performance at critical times and meet new national guidelines for restricted physician hours. Abstracts have been accepted on this scheduling work and will be presented at national and international meetings.
We are developing new methods to refine the scheduling algorithm for predicting individual differences in circadian phase and performance. We are individualizing predictions based on easily collected trait information (e.g., age, chronotype), and developing a statistical framework for making individual predictions. Experimental evidence demonstrates changes in physiology are well correlated with age and specialized questionnaire results (e.g., habitual sleep time is highly correlated with circadian phase). The work of Dr. Andrew Phillips (NSBRI postdoctoral fellow) has quantified mechanisms underlying individual differences in physiologically-determined sleep timing and self-reported (subjective) chronotype (e.g., “owl” or “lark”).
Using synergistic support from a NIH “Grand Opportunities” grant to Dr. Klerman, we are developing and populating a database with studies from the Brigham and Women’s Hospital (BWH) Division of Sleep Medicine. The database has enabled a larger data set for our modeling work and will facilitate the building of individual models using demographic data as described above.
To assess the ability of individuals to conform to scheduled work hours, Dr. Phillips is integrating the circadian and performance model with a model of the physiological mechanisms which control sleep-wake transitions. This combined model dynamically predicts wake/sleep state across a simulated protocol, allowing predictions of sleep efficiency, and likelihood of falling asleep during scheduled wake periods. This model has been validated using BWH datasets; several abstracts have been published on this work. Since the model is physiologically based, it is being extended to incorporate pharmaceutical effects, including simulating the effects of melatonin and caffeine at different times and dosages. We are targeting the use of actigraphy, which is an inexpensive and less intrusive alternative to polysomnography, to determine sleep/wake state and then use the mode to predict circadian phase and performance without other inputs. Several abstracts have been published on this work.
Our NSBRI-funded work is broadly applicable to diverse work environments, ranging from NASA missions to industries such as aviation, transportation, and the military. We are also working with the NSBRI Industry Forum to explore ways to facilitate use of our work in these diverse environments. We continue to work with NASA and NSBRI personnel to meet their requests regarding use of the models and software.
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Principal Investigator:
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Elizabeth B. Klerman, M.D., Ph.D.
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Organization:
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Harvard-Brigham and Women's Hospital
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Project Ended:
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2012
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The development of mathematical models of circadian rhythms, sleep, alertness and performance, and of software based on these models that aid in schedule design, can improve performance, alertness, effectiveness and public safety for people who work at night, on rotating schedules, on non-24-hour schedules, or extended duty schedules (e.g., pilots, train and truck drivers, shift workers, health care workers, public safety officers).
Attempting to sleep at adverse circadian phases is difficult, resulting in poor sleep efficiency. Similarly, attempting to work at adverse circadian phases and/or after long durations of time awake results in poor worker performance and productivity, as well as increased errors. For example, the accidents at the Chernobyl and Three Mile Island nuclear reactors and the Exxon Valdez grounding were all partially attributed to employees working at adverse circadian phases.
The mathematical models and the available Circadian Performance Simulation Software (CPSS) can be used to simulate and quantitatively evaluate different scenarios of sleep/wake schedules and light exposure to predict the resulting circadian phase and amplitude, subjective alertness and performance. CPSS has been requested by members of academia, government and industry, including airline, safety, medical and military applications. Its use could help produce improved work schedules for those people working in space and on Earth.
The recent incorporation of actigraphy as input to the mathematical model as a tool to record sleep has improved the confidence levels on the daily assessment of sleep when compared to the use of sleep logs. The interface between actigraphy and CPSS enables faster and possibly more accurate predictions of circadian phase and performance parameters. The software now also includes optimal countermeasure design, so that countermeasures can be planned for times of predicted poor performance and alertness. The schedule/countermeasure design program allows users to interactively design schedules and implement mathematically optimal light countermeasures (including intensity, duration and placement) to minimize worker fatigue. This scheduling software will be valuable to those who work at night, on rotating schedules, on non-24-hour schedules or extended duty schedules. Individuals can design countermeasures for their assigned work schedules, so that their sleep and wake rhythms will be adjusted for optimal performance at desired times, both with respect to scheduled work events and circadian phase. Improving sleep duration and quality can also decrease the risk of accidents and errors, as well as decrease the long-term risks of cardiovascular, metabolic, immune and psychological pathologies.
The mathematical modeling has been used for basic scientific research. Inclusion of mathematical models in the planning process to optimize measures to be studied in experimental protocols enables more efficient use of research resources and directs new research. If the modeling of existing experimental data is found to be unsatisfactory, then model assumptions may need to be revised; this revision may include identification of a new physiological process not previously described.
The mathematical modeling efforts and software have also been used in educational programs and in the popular press to teach students, teachers and health care professionals about circadian rhythms and sleep, work schedules and their effects on alertness and performance.
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