Appendix A

NASA Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions A. Funding Opportunity Description

1. Introduction Note: All citations of the Human Exploration Research Opportunities (HERO) Overview document refer to the 2019 version posted alongside this Appendix at HERO Overview at https://nspires.nasaprs.com/external/.

To be responsive to this research solicitation, proposed studies should lead to specific products that address at least one of the three specific objectives outlined in the Human Exploration Research Opportunities (HERO) Overview document, section B.2, Goal and Specific Objectives. The proposed studies should lead to new knowledge within accepted scientific standards. Proposals should take into account the impact of sex, age, nutrition, stress, genetic predisposition, or sensitivity on other factors of importance. A thorough statistical section must be included which includes a power analysis for the estimate of sample size. When archival samples are available, the comparison of males and females should be included in the statistical section unless compelling evidence is provided that shows that no sex differences are expected. Please see the Sample Size Specification Guidelines posted on the NASA Solicitation and Proposal Integrated Review and Evaluation System (NSPIRES) solicitation download site alongside the HERO Overview document for additional information concerning sample size calculations. Proposers that request NASA archived data should fill out the Retrospective Data Request Study Feasibility Assessment Form posted alongside the HERO Overview document.

Proposals must be responsive to the research emphases outlined below in order to be reviewed as significant to the goals of this solicitation. The proposed research approach must adhere to all constraints and guidelines outlined in this solicitation.

2. Research Emphases Research in the Human Research Program (HRP) is organized around 32 risks and two concerns as outlined in the Human Research Roadmap (https://humanresearchroadmap.nasa.gov/Risks/). In the current Appendix, HRP is soliciting research for the following topics:

Topic 1: Effects of G-levels between 0 and 1 Induced by Parabolic Flights on Human Neurovestibular and Sensorimotor Systems

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Primary Risk Relevant Gap Risk of Impaired Control of CBS-SM2.1: Determine the changes in sensorimotor function Spacecraft/Associated over the course of a mission and during recovery after landing. Systems and Decreased CBS-SM28: Develop a sensorimotor countermeasure system Mobility Due to integrated with current exercise modalities to mitigate Vestibular/Sensorimotor performance decrements during and after spaceflight. Alterations Associated with CBS-SM6.1: Determine if sensorimotor dysfunction during Spaceflight and after long-duration spaceflight affects ability to control spacecraft and associated systems. CBS-SM24: Determine if the individual capacity to produce adaptive change (rate and extent) in sensorimotor function to transitions in gravitational environments can be predicted with preflight tests of sensorimotor adaptability.

Secondary Risk Relevant Gap Risk of Acute (In-flight) and CBS-CNS-5: How can new knowledge and data from Late Central Nervous System molecular, cellular, tissue and animal models of acute CNS Effects from Radiation adverse changes or clinical human data, including altered motor Exposure and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE? CBS-CNS-8: Are there significant CNS risks from combined space radiation and other physiological or space flight factors, e.g., psychological (isolation and confinement), altered gravity (micro-gravity), stress, sleep deficiency, altered circadian rhythms, hypercapnea, altered immune, endocrine and metabolic function, or other?

Risk of Adverse Cognitive or CBS-BMed2: We need to identify and validate measures to Behavioral Conditions and monitor behavioral health and performance during exploration Psychiatric Disorders class missions to determine acceptable thresholds for these measures.

Risk of Injury and EVA 11: How do EVA operations in exploration environments Compromised Performance increase the risk of crew injury and how can the risk be Due to EVA Operations mitigated

Summary Spaceflight-related studies have shown that perception of self-orientation, gaze, posture, as well as eye, hand, and body movements are altered by 0 G exposure (Clément & Reschke, 2008). The G-threshold, for which these decrements occur, and how these thresholds may adapt or change as

Appendix A - 5 a result of combined spaceflight factors (e.g., stress and radiation effects on CNS), are currently unknown.

With plans underway for returning to the lunar surface in the mid-2020s as a stepping stone to future Mars landings, knowledge on the relationship between sensorimotor and neurovestibular variables (dependent variables) and G-levels between 0 and 1 (independent variables) is required. G-levels of 0, 0.25, 0.50, 0.75, and 1 will be induced by parabolic flights, each G-phase lasting approximately 20 s, except for the 1-G level, which will be longer (straight and level flight). Immediately before and following the partial G levels, subjects will be exposed to increased G’s of up to 1.8 for approximately 20 s. In addition to measures obtained during the partial G phases, measures can also be obtained during the high G phases, which could be of importance for understanding effects of G-transitions from high to low as well as from low to high.

Background NASA is currently in the process of revising its crewed space mission strategies to include lunar landings in the mid-2020s. This will be a perfect stepping stone to test various physiological health outcomes under low, lunar G-exposures. Very little is generally known about the physiological effects of exposures to G-levels between 0 and 1 (Paloski & Charles, 2014; Fig. 1), mainly due to the fact that on the surface of the Earth these G-levels cannot be accurately simulated because of Earth’s ever present gravitational effects of 1 G.

Figure 1. The dose response curve of physiology response versus G-force between 0 and 1 is unknown in humans (adapted from Paloski & Charles, 2014).

The present topic is being specifically issued in order to determine how human neurovestibular and sensorimotor variables of operational relevance to health and space mission success correlate with effects of G’s between 0 and 1.

A well-functioning neurovestibular and sensorimotor system is pivotal for an astronaut to conduct mission related tasks at all phases of a space mission. These systems are particularly sensitive to G-transitions. Much is known about the transition from 1 to 0 G and vice versa, and

Appendix A - 6 in particular the latter effects have been very thoroughly described by Mulavara et al. (2018). These authors have related sensorimotor function to mission-related post-landing task tests. Miller et al. (2018) also investigated the immediate post-flight effects of spaceflight on various functional performance tests and related the outcomes to mission duration. By adding a bed rest component to the study, they could also relate the effects of exercise to post-bed rest performance outcomes and concluded that exercise per se is not sufficient to maintain an intact sensorimotor system.

Specific Research Focus Area Since very little is known about the lunar and Martian gravity effects on the neurovestibular and sensorimotor systems, this topic seeks proposals that focus on the immediate sensorimotor and neurovestibular effects of various G-levels between 0 and 1 in order to establish a dose-response curve between sensorimotor- and neurovestibular-controlled performance outcomes versus the G-levels. This will allow us to detect G-thresholds for preliminary predictions of how much of a decrement in G is needed to affect these neural control systems, and at which G-level the systems are protected by gravity. Since G-transitions occur during parabolic flight, the neurovestibular effects of transitions from an immediate high (1.8) to various immediate low-G levels can also be established, which might be informative for understanding disruptions during landings on various planetary surfaces.

The limitations of using very short-term G-interventions by parabolic flight maneuvers are obvious, so proposals should only aim for monitoring fast responding variables that are sensitive to G’s and which are of relevance to operational performance.

Note that only human subjects are allowed for this topic. Animal models are not allowed.

Research Platform Parabolic flight, which can deliver G-levels of 0.00, 0.25, 0.50, 0.75, and 1.00 (straight and level flying).

Required Deliverables  A dose-response relationship between key human neurovestibular/sensorimotor variables of operational relevance for spaceflight versus G-levels between 0 and 1.  Understanding the G-threshold effects on human sensorimotor/neurovestibular sensitivity and function.

Award Information Please note that a maximum of $200,000/year for two years (total = $400,000) is available for this topic.

A summary of the current evidence for these risks, and a reference list, is available at https://humanresearchroadmap.nasa.gov/evidence/.

For technical, programmatic, and solicitation matters:

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Contact Peter Norsk, M.D.; Element Scientist, Human Health Countermeasures Telephone: 281-244-5405 E-mail: [email protected]

References Clément G, Reschke MF (2008) Neuroscience in Space. Springer: New York.

Paloski WH and Charles JB. 2014 International Workshop on Research and Operational Considerations for Artificial Gravity Countermeasures. NASA/TM-2014-217394.

Mulavara AP et al. (2018) Physiological and Functional Alterations after Spaceflight and Bed Rest. Med. Sci. Sports Exerc. 50: 1961-80.

Miller CA et al. (2018) Functional Task and Balance Performance in Bed Rest Subjects and Astronauts. Aerosp. Med. Hum. Perform. 89: 805-15.

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