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 (e.g., zolpidem, ramelteon, etc.) on ISS.

1. Develop improved methods of unobtrusively measuring workload during a mission, working toward an advanced system that could detect inadequate workload (too low or too high) and make recommendations. A method should be developed, tested, and validated for use in a spaceflight environment.

1. Complete a flight study to validate the recommended measures for Crew Resource Management (CRM), Situation Awareness (SA), and Workload that were produced in the previous solicitations. A 1-year mission would be an ideal mission for this validation.

The overarching goal of this project is 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 (SBMT) that would be quite 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.

This task also informs Sensorimotor discipline areas: SM 2.1, SM 6.1, SM 28

This study aims to test and implement the NeuroCATs toolkit on the ISS-12 mission.  This will permit rapid assessment of performance in cognitive, social-emotional and sensorimotor domains and help inform whether cognitive changes may exist over an extended duration in space.

Aim 1. Provide a set of BHP standard measurements for investigators to use in proposed projects.

Aim 2. Enable comparison of multiple missions across analog campaigns to quantify risk using reliable metric-based data.

Aim 3. Provide database for data-mining and integrative modeling and increase research data quality and transfer to LSDA.

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 (e.g., zolpidem, ramelteon, etc.) on ISS.

In their evaluation of rodents, researchers from the University at Rochester have recently discovered that cerebral spinal fluid moves quickly and deeply into the brain to flush out cellular waste and minimize neuronal plaque (the hallmark of Alzheimer's). This process is approximately 80% more efficient when we sleep.

The purpose of this task is to conduct a study using head-down-tilt that evaluates the relationship between chronic sleep loss and changes in the glymphatic system, which is particularly relevant given the fluid shifts that occur in spaceflight. Results from the study will inform the likelihood and consequence of this risk.

In their evaluation of rodents, researchers from the University at Rochester have recently discovered that cerebral spinal fluid moves quickly and deeply into the brain to flush out cellular waste and minimize neuronal plaque (the hallmark of Alzheimer's). This process is approximately 80% more efficient when we sleep.

The purpose of this task is to assess the literature on the relationship between chronic sleep loss and changes in the glymphatic system, which is particularly relevant given the fluid shifts that occur in spaceflight. This effort will help to define follow-on investigations that may be needed.

The intent of this task is to evaluate sleep data from the largest, most systematic assessment of sleep in space (Barger et al., 2014), relative to performance outcomes in space, such as cognitive performance and operational performance (if accessible).

1. Develop improved methods of unobtrusively measuring workload during a mission, working toward an advanced system that could detect inadequate workload (too low or too high) and make recommendations. A method should be developed, tested, and validated for use in a spaceflight environment.

1. Complete a flight study to validate the recommended measures for Crew Resource Management (CRM), Situation Awareness (SA), and Workload that were produced in the previous solicitations. A 1-year mission would be an ideal mission for this validation.

Task design and related hardware and software impose cognitive and physical demands on an operator, and thus drive the workload associated with a task. Astronauts on long-duration missions will potentially have long periods of low workload and short bursts of high workload combined with reduced workload capacity that need to be taken into account for system and mission design. Both high task demand and reduced workload capacity at any phase of a flight may lead to performance errors, which could potentially compromise mission objectives, and consequently the mission. An unobtrusive workload tool is needed during system development to ensure that the use of the system is associated with acceptable workload, as well as during real-time use of systems, to drive schedule modifications or to adapt interfaces based on the current workload the astronaut is experiencing.

1. Based on the current state of the art and recommendations from the Phase1 effort develop a workload tool prototype to measure, assess, and predict astronaut workload unobtrusively.
2. Test and validate the tool. The technology should also be predictive of astronaut workload during long-duration operations.

The task will contribute to gap closure by providing an unobtrusive workload measurement tool for long-duration missions.

Study Aim:  Characterize the behavioral health and performance effects of a simulated Long Duration Exploration Mission (LDEM) in HERA on flight performance, workload, and situation awareness during representative spaceflight operational tasks.

A series of experiments will be conducted using the simulated spaceflight scenarios and real-time metrics engine to quantify performance, workload, and situation awareness in each task during the HERA mission. Analysis will be conducted for each scenario and meta-analysis across scenarios will be conducted to determine commonalities and to determine absolute performance thresholds. These metrics will also be correlated to data collected as part of the BHP Standardized Measures, including sleep/wake cycle, actigraphy, and a cognitive battery.

Deliverables include the analysis of data collected during these HERA missions, in the form of publishable research results, that can be directly used to address the HRR Risks and Gaps.

Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.

Aim 3: Identify physiological or behavioral variables that predict operational performance.

Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.

Aim 1: Perform individualized analyses and modeling of our extensive laboratory data set from inpatient studies ranging from 4-74 days including biomarkers such as sleep (EEG, actigraphy, logs); repeated measures of neurocognitive performance including attention, vigilance, motor control, and short-term memory; repeated measures of alertness (waking EEG, subjective scales); circadian phase (melatonin, cortisol, temperature); stress and activation (heart rate variability, blood pressure, catecholamines, cortisol), metabolism (lipid metabolism, glucose metabolism), immune function (cytokine and chemokine rhythms) and mood (clinical questionnaires, subjective scales) and multiple other physiological and metabolic measures.

Aim 2: Conduct a series of short 7-day inpatient studies on astronaut-aged healthy male and female volunteers to test the sensitivity and specificity of multiple biomarkers to predict inter-individual responses to sleep and circadian challenges.

Aim 3: Evaluate the feasibility and utility of implementing a standardized set of objective and subjective predictive biomarkers for neurocognitive impairment and behavioral health outcomes in Antarctica.

This task is on the BMed Critical Path

Software using mathematical models can help inform assessments related to work-rest schedules and implementation of fatigue countermeasures.  Branches of the military, for example, use the Sleep, Activity, Fatigue and Task Effectiveness (SAFTE) model to predict performance effectiveness relative to sleep-wake history.  Other relevant modeling efforts have included the development of the Circadian Performance Simulation Software (CPSS) by Brigham and Women’s Hospital, and the Individualized Fatigue Meter by Pulsar Informatics.  NASA, the National Space Biomedical Research Institute, and other agencies have supported the development of such software solutions to provide predictions of performance capability relative to sleep-wake history.   Software solutions can inform real-time task scheduling decisions and aid implementation of countermeasures such as caffeine and lighting – especially important, given that the proper scheduling of such countermeasures is essential to their effectiveness.

Mathematical models can therefore be used operationally in future space exploration missions, to inform the scheduling of mission-related tasks and the timing of fatigue-related countermeasures. This topic is soliciting proposals to evaluate the use of such a tool, as a means through which autonomous crews in a simulated spaceflight mission can appropriately implement fatigue-related countermeasures, and for understanding how a crew medical officer (who would be a participant in the study) and/or an individual crewmember will use the information to make countermeasure recommendations and real-time scheduling changes.

This task seeks to assess, in an operational environment (the Habitat Exploration Research Analog, or HERA, at Johnson Space Center), the acceptability, usability, and overall feasibility of sleep-wake models and associated software, to make informed decisions for long-duration space exploration missions (LDEMs), when ground support will be minimized and crews will function more autonomously.

Create a web-based framework for integrating non-coding genomic variation and differential epigenetic states. This EpiSuite interface and set of machine-learning algorithms will help ongoing work with the NASA Twins study and aid future investigations that leverage multi-omics data sets from astronauts. These data will also be linked to gene expression data to gauge the impact of genetic

and epigenetic changes on specific biological networks.

Validate the altered chromatin states in cells from space travel and measure the proportion of cells changed with single-cell ATAC-seq using an assay called single cell (scATAC-seq), which can measure the sites of open and closed chromatin on a cell-by-cell basis. This will validate the sites where epigenetic changes are observed and also provide the first estimate of the proportion of

cells epigenetically impacted by space travel.

Aim 1. Provide a set of BHP standard measurements for investigators to use in proposed projects.

Aim 2. Enable comparison of multiple missions across analog campaigns to quantify risk using reliable metric-based data.

Aim 3. Provide database for data-mining and integrative modeling and increase research data quality and transfer to LSDA.