Past Research

Astronauts are required to maintain optimal neurobehavioral functioning despite chronic exposure to the stressors and challenges of spaceflight. Sleep of adequate quality and duration is fundamental to neurobehavioral functioning, however astronauts commonly experience short sleep durations in spaceflight (<6 h). As humans embark on long-duration space exploration missions, there is an outstanding need to identify the consequences of sleep deficiency in spaceflight on neurobehavioral functions. Therefore, we conducted a longitudinal study that examined the sleep-wake behaviors, neurobehavioral functions, and ratings of stress and workload of N=24 astronauts before, during, and after 6-month missions aboard the International Space Station (ISS). The Psychomotor Vigilance (PVT) Self Test (operational name on ISS is Reaction Self Test) was intended to provide astronauts with objective feedback on neurobehavioral changes in vigilant attention, psychomotor speed, state stability, and impulsivity while on ISS missions. The PVT Self Test is ideal for repeated use in spaceflight because unlike other cognitive tests, it is very brief (3-minute) while being free of learning effects and aptitude differences that make interpretation of other cognitive measures difficult. The ultimate goal of the Reaction Self Test project was to validate the sensitivity of the PVT Self Test on astronauts on ISS so they can use it to objectively identify when their performance capability is degraded by various fatigue-related conditions that can occur as a result of ISS operations and time in space. The objectives (specific aims) of the project were:

1) To evaluate the extent to which PVT Self Test performance of astronauts is sensitive to fatigue from sleep loss and circadian disruption during ISS missions. This will include the following conditions evaluated individually and in aggregate: i) extended wake duration between 16 hours; ii) sleep restriction defined as total sleep time >0 and <6 hours per 24-hour period; and iii) circadian perturbation associated with night work and slam shifting.

2) To evaluate the extent to which PVT Self Test performance of astronauts is sensitive to fatigue from work intensity during ISS missions. This will include the following conditions evaluated individually and in aggregate: i) extend work durations up to 16 hours per day; ii) more than 6 consecutive work days without a day off for rest; and iii) work requiring extravehicular activity (EVA).

3) To evaluate the extent to which PVT Self Test performance of astronauts declines with time in mission.

4) To explore the extent to which PVT Self Test performance of astronauts will be sensitive to the carry-over effects of medications for sleep on ISS.

5) To evaluate the extent to which PVT Self Test performance feedback (via a graphical interface) is perceived by ISS astronauts as a useful tool for assessing performance capability.

Reaction Self Test Publications

Jones, C.W., Basner, M., Mollicone, D., Mott, C., Dinges, D. F.: Sleep deficiency in spaceflight is associated with degraded neurobehavioral functions and elevated stress in astronauts on six-month missions aboard the International Space Station. Sleep. 2022 Mar 14;45(3):zsac006. doi: 10.1093/sleep/zsac006. PMID: 35023565; PMCID: PMC8919197.

Tu, D., Basner, M., Smith, M.G., Williams, E.S., Ryder, V.E., Romoser, A.A., Ecker, A., Aeschbach, D., Stahn, A.C., Jones, C.W., Howard, K., Kaizi-Lutu, M., Dinges, D.F., Shou, H.: Dynamic ensemble prediction of cognitive performance in spaceflight. Sci Rep. 2022 Jun 30;12(1):11032. doi: 10.1038/s41598-022-14456-8. PMID: 35773291; PMCID: PMC9246897.

This study utilizes Reaction Self-Test (RST) data collected by the PI and his team in N=24 astronauts on 6-month ISS missions, arguably the largest cognitive data set ever collected in spaceflight. RST consists of a survey module and a3-minute version of the Psychomotor Vigilance Test (PVT). Our main objective is to additionally obtain data on key environmental stressors (i.e., CO2 levels, temperature, noise, and radiation) and combine them with RST data and other operational data collected by the PI and his team. All data will be integrated in one carefully annotated database, which will be delivered to NASA at the end of the project and could be later amended and mined by other researchers. We will then develop an individualized dynamic prediction model that informs future PVT performance based on environmental data, survey data, prior PVT administrations, and person-specific characteristics using state-of-the-art machine learning techniques such as functional concurrent regressions and neural networks for time series forecasting. We will perform model selection and identify those variables that have the highest predictive value for PVT performance and could preferentially be collected on future spaceflight missions to inform relevant changes in cognition and behavioral health. At the end of the study, we will deliver an algorithm to NASA that, for the first time, can predict adverse cognitive conditions in astronauts early and with an unprecedented precision (Deliverable 3). The predictive algorithms can be translated to several settings on Earth where high performing individuals have to sustain high levels of cognitive performance while facing several environmental or other challenges (e.g., US Navy personnel on submarines).

This proposal addresses the risk of Adverse Behavioral Conditions and Psychiatric Disorders, and the need to identify and validate countermeasures and effective methods for modifying the habitat/vehicle environment that promote individual behavioral health and performance during exploration class missions (BMed1, BMed7). We propose to investigate the efficacy of physical exercise (using a cycle ergometer) combined with an interactive virtual environment, i.e. Hybrid Training, as a countermeasure for augmenting sensory stimulation during long-duration space missions. This countermeasure will combine validated tools and VR technologiesin a new way to reveal the full potential of Hybrid Training, and take into account (a) key needs that fulfill sensory stimulation, (b)“hedonic adaptation”, i.e. a reduced affective response to stimuli with continued or repeated exposure, (c) delivery schedule, and (d)size, mass and volume requirements. We plan to investigate a crew of N=9 during two 12-14 month Antarctic winter-over missions in Neumayer station (total N=18). We will investigate both immediate and long-term benefits of Hybrid Training. Our primary outcomes are neurostructural and neurofunctional changes assessed with fMRI, and cognitive performance assessed with the Cognition test battery and a virtual maze. We will also assess biochemical markers of stress and neuroplasticity, objective measures of sleep-wake rhythmicity and sleep structure, subjective symptom reports, and group cohesion with unobtrusive proximity measurements as additional outcomes that will provide insights into mechanisms and consequences of the observed structural and functional brain changes, and their reversibility by Hybrid Training. These data will be compared to historic controls from Neumayer station and other Antarctic stations (Concordia, Halley), space analog environments (e.g., Mars500) and the ISS. At the end of the project, we will have a much clearer understanding whether and to what extent the detrimental effects of ICE environments on neuroplasticity and behavioral health can be mitigated by Hybrid Training.

Astronauts must maintain a high level of cognitive performance capability in spaceflight, which depends on their acquiring adequate daily sleep quantity and sleep quality while in space, and on their ability to respond quickly and effectively to emergency events that can occur when they are asleep. However, chronic sleep restriction (i.e., sleep durations <6.5h) and astronauts’ perceptions of poor sleep quality are common in spaceflight missions. Sleep medications have been used to promote sleep in spaceflight, although they can impair neurobehavioral and cognitive performance of astronauts when an emergency awakening requires them to function effectively. Thus, there is a need to develop alternative countermeasures that can improve sleep quality in space and biologically maximize the performance benefits of sleep without unduly affecting the ability of astronauts to awaken abruptly to an inflight emergency, or the carryover effects of sleep medications.

Evidence suggests that many of the benefits of sleep are associated with sleep EEG slow waves and that subjective sleep quality is related to the size and number of these slow waves. Studies have found that acoustic enhancement of EEG slow waves during sleep not only increases EEG slow-wave activity (EEG power: 0.5-4 Hz band), but also post-sleep cognitive performance. The SmartSleep Deep Sleep Headband, developed by Philips, is an EEG slow-wave enhancing technology that monitors and stages sleep EEG in real-time and delivers auditory stimulation during non-REM sleep in a closed-loop fashion at a volume that is dynamically modulated by sleep depth. Although studies suggest that the EEG slow-wave enhancement can deepen sleep and subsequently improve declarative memory and cognitive performance in non-restricted sleep periods, the utility of acoustic stimulation and the SmartSleep technology during sleep restriction is unknown.

The overarching goal of this project was to evaluate whether the adverse effects of chronic sleep restriction on neurocognitive functions could be mitigated by auditory brain stimulation during sleep using the SmartSleep technology. To achieve this goal, a 7-day (6-night) laboratory was conducted where participants were provided a baseline sleep opportunity of 8 h, followed by 4 consecutive nights of 5 h sleep opportunity (sleep restriction [SR]). Participants wore the SmartSleep headband on study all nights and on SR nights, they received one of three SmartSleep auditory stimulation conditions, as well as one SHAM condition (i.e., no auditory stimulation). The order in which participants received each SmartSleep auditory stimulation condition varied by subject to systematically evaluate the effect of SmartSleep auditory stimulation conditions across nights of SR. Participants completed the Cognition test battery, which includes 10 assays of cognitive performance, three spaceflight-relevant operational performance tasks, and a spatial cognition test repeatedly within and across all days of the laboratory study.

The overarching aim of this study is to investigate the effects of 60 days of head down tilt bed rest (HDBR) with and without artificial gravity as a countermeasure on structural and functional brain plasticity and their behavioral significance. The experiment will comprise the following specific aims:

• Investigate the effects of HDBR with and without artificial gravity on gray and white matter volume, subcortical volume, myelination, functional connectivity and task related brain activation.
• Investigate the effects of HDBR with and without artificial gravity on cognitive performance
• Investigate the effects of HDBR with and without artificial gravity on biochemical markers of stress and neuroplasticity

All experimental procedures will be conducted on N=24 enrolled subjects in an ongoing 60-day HDBR study sponsored by the European Space Agency (ESA) at the DLR: envihab facility. This 2-year project (approx. 1 to 1.5 years data collection; remainder for analysis) will deliver a comprehensive set of neuroimaging, neurocognitive and physiological assessment tools for the evaluation and ultimately prevention of adverse neurostructural and neurobehavioral effects associated with spaceflight.

In the US and other countries, policy limiting duty hours in graduate medical education has undergone significant revision in the last decade and become a central point of debate. Evidence from human chronobiology and sleep argues for shorter shifts because fatigue leads to errors. However, evidence from operations research argues for more continuity because patient handoffs also lead to errors and may reduce the effectiveness of education necessary to produce independent clinicians. The evidence from both fields is compelling, resulting in uncertainty regarding how to best configure duty hour standards for fatigue management, high quality patient care, and trainee education. In 2011, the Accreditation Council for Graduate Medical Education (ACGME) imposed more restrictive duty hour standards for all trainees. The new duty hours added that post-graduate year 1 (PGY1) trainees (interns) work no more than 16h duty periods in a day. This change greatly increased the frequency of patient handoffs. As a result, alternative work schedules have been proposed that combine longer shifts to maintain continuity of patient care with efforts to manage fatigue.

We propose a cluster randomized trial of 58 Internal Medicine (IM) training programs to compare the current duty hour standards (“Curr” throughout this proposal) with a more flexible schedule (“Flex”) that is grounded in contemporary understanding of sleep and patient safety and defined by three rules: [1] work no more than 80 hours per week; [2] call no more frequent than every 3rd night; [3] 1 day off in 7—all averaged over 4 weeks.

Our primary hypothesis addresses patient safety: 30-day patient mortality under Flex will not exceed (will not be inferior to) mortality under Curr. Our secondary hypotheses address education and sleep and fatigue: (a) Interns in Flex will spend greater time in direct patient care and education compared to interns in Curr; (b) Average daily sleep obtained by interns in Flex will not be less than (will not be inferior to) that of interns in Curr.

iCOMPARE (Individualized Comparative Effectiveness of Models Optimizing Patient Safety and Resident Education) will provide the rigorous comparative effectiveness data essential to setting duty hourpolicies that optimize quality of care and the competency of our future physicians. Moreover, the same two schedules, Curr vs. the novel Flex scheme, are being compared in the ongoing FIRST trial in residents in general surgery. The combination of well-designed separate trials in both primarily procedural and nonprocedural fields will fill the unmet need for a high-quality, generalizable body of evidence to inform national duty hour policy.

Despite decades of development of antidepressant treatments, even the most effective interventions often take weeks to achieve symptom relief, and are only effective in a subset of patients who try them. From 40 to 60%of patients with depression experience a rapid and significant improvement of mood with one night of total or partial sleep deprivation (SD). Although the antidepressant effect of SD has been known for decades, the neural mechanisms underlying this effect have not been elucidated. Recent advances in functional neuroimaging have provided new opportunities to investigate state changes in regional brain function, along with a better understanding of the neural networks affected by depression and SD. Previous depression studies from our group as well as others have consistently demonstrated dysfunction in brain networks underlying arousal, emotion regulation, and self-referential processing. Our neuroimaging data in healthy controls shows that SD can change the function of these same networks and these changes are opposite to that seen in depressed patients versus controls. Here we propose to study a group of N=48 antidepressant-free male and female patients with current depression symptom and N=12 healthy controls with no history of mood disorders before and after SD to provide mechanistic insight into the neural substrates underlying the antidepressant effects of SD. We hypothesize that SD-induced concurrent functional activity and connectivity changes in multiple brain networks related to different depressive symptom dimensions including emotion regulation, attention, arousal, self-referential, and reward processing will underlie the rapid and transient antidepressant effects of SD. Using an ABA design, multimodal brain imaging along with more traditional electroencephalographic (EEG) and neurobehavioral testing data will be acquired at baseline after normal sleep, during one night of total SD, and after one night of recovery sleep using a 5-day in laboratory protocol during which subjects will be continuously monitored by trained staff. An interdisciplinary team of researchers with expertise in depression, neuroimaging, sleep, and chronobiology will collaborate to carry out this project using state-of-the-art approaches. Results from this project will not only elucidate neural mechanisms underlying the rapid antidepressant effects of SD, but also yield brain-based biomarkers to predict or monitor individual responses to SD and potentially novel targets for pharmacological and neuromodulatory interventions.

The behavioral health of the crew during a mission to Mars could be challenged due to conditions required by the flight. However, there is no standardized method to detect and quantify the magnitude of the risk or its likelihood. The overarching goal of this project was to build on a successful record of unobtrusive, software-based measurement of behavioral health indicators (e.g., mood, cognitive function, physical and mental fatigue, sleep quality) to develop an integrated standardized suite of behavioral health measurement tools that would be feasible to implement within the constraints of spaceflight research, ground-based analogs (both short- and long-duration), and prolonged missions in isolated, confined, extreme environments lasting up to 12 months or longer. Achievement of this goal was expected to permit a more rapid and reliable assessment and quantification of the NASA’s Human Research Roadmap Risk of Adverse Behavioral Conditions Psychiatric Outcomes for exploration class missions. The suite of behavioral medicine measures developed were integrated on Apple's iPad platform for their standardized use in ground analogs relevant to the spaceflight context (i.e., Standardized Behavioral Measures Tool or SBMT). The suite of SBMT includes (a) the Cognition battery, (b) Visual Analog Scales (VAS) of perceived mental and physical exhaustion, fatigue, stress, workload, conflict and sleep quality, (c) actigraphy for objective monitoring sleep/wake activity, (d) an audio journal, (e) the Robotics On-Board Trainer research (ROBoT-r) as an operational performance measure, and (f) additional non-invasive measures relevant to behavioral medicine informed by a comprehensive literature review. The SBMT was evaluated for its feasibility, including the task of taking the information on measurement feasibility, flexibility, and acceptability during post-mission assessments in the participants studied in spaceflight analog environments, including the Human Exploration Research Analog (HERA), Neumayer-III Antarctic station, and the International Space Station (ISS). The SMBT was improved and an operational document was developed to make its use convenient and unobtrusive for detecting the incident rate of behavioral health risks in space and on Earth.