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NASA NTRSDate not supplied

Neuroimmune responses to space radiation

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 0.3-0.8Gy 600MeV/n 56Fe ions; as well as to 0.5-1Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by damage to endothelial cells and tight junctions, altered cytokine expression including TNFalpha upregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively induced astrocyte damage and increased blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Furthermore, in our lab we have been exploring the individual variability, genomic associations and secreted biomarkers of responses to space radiation, which could eventually be combined to address personalized CNS health risk and develop individual countermeasures. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗

NASA NTRSDate not supplied

Neuroimmune Responses to Space Radiation

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 600MeV/n 56Fe ions. We observed ionizing radiation-mediated dose-dependent increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by altered cytokine expression including interleukin-1 receptor alpha downregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively increased damage and blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Furthermore, in our lab we have been exploring the individual variability, genomic associations and secreted biomarkers of responses to space radiation, which could eventually be combined to address personalized CNS health risk and develop individual countermeasures. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗

NASA NTRS2021

Chemical Reactivity of In-Situ Lunar Dust for Biotoxicity Assessment

How does the chemical reactivity of in-situ lunar dust compare to Apollo samples currently stored in curation facilities here on Earth? Essential investigations of this question will help us to further mitigate exploration risks for future human explorers on the Moon and will also provide critical information for astrobiologists and space biologists using the Moon for scientific inquiry. Apollo 14 dust biotoxicity studies, carried out by the NASA Lunar Airborne Dust Toxicity Assessment Group (LADTAG), included numerous cellular and animal experiments. Intratracheal instillation and inhalation studies in rats both showed Apollo 14 dust to be intermediate in toxicity compared to low-tox titanium dusts and high-tox quartz dusts of similar particle sizes. The collective results were used in models to establish a safe exposure limit for astronauts. Although LADTAG took extensive steps to preserve what chemical reactivity may still have existed in the samples, it is simply unknown if they possessed true in-situ chemical reactivity or if that reactivity has decayed. Initial gas loss on collection and other alterations, and even intermittent exposure to Earth-normal conditions during subsequent decades of handling, obscure a forensic reconstruction of the initial state. Because a mineral dust’s chemical reactivity influences its biotoxicity, researchers have developed methods to “activate” lunar dust and simulants. Past studies that modeled impact processes and radiation in the lunar environment suggest that in-situ lunar dust is likely to be more chemically reactive than Earth-exposed samples. Because of these results, in-situ measurements are warranted. Since the lunar surface is heterogeneous, dust biotoxicity is expected to vary from site to site due to particle size, mineralogy, physical characteristics, degree of space weathering, and chemical reactivity. This circumstance dictates dust assessments at a suite of lunar sites enabled by CLPS opportunities. Dose, location, and duration of particle exposure will also affect biological responses. In-situ chemical reactivity measurements can inform cross-cutting collaborative research campaigns such as astrobiology studies examining regolith interactions with organisms and its ability to preserve chemical and structural biomarkers, as well as space biology investigations that examine regolith-microbe interactions relating to life support systems, plant growth, biomining, and development of regolith biocomposites.

Jon C Rask↗

NASA NTRSDate not supplied

Beyond Low-Earth Orbit: Characterizing Immune and microRNA Differentials Following Simulated Deep Spaceflight Conditions in Mice

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared to data from astronauts on ISS missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed involvement in immune system dysregulation. Furthermore, a large astronaut cohort showed elevated inflammation during LEO missions, thereby supporting our simulated ground experiments in mice. Herein, circulating immune biomarkers are defined by distinct deep space irradiation types coupled to simulated microgravity and could be targets for future space health initiatives.

deep spaceflight stressors↗

NASA NTRS2003

Ballute aerocapture trajectories at Titan

One of humanity’s oldest questions is whether life exists elsewhere in the universe. The Terrestrial Planet Finder (TPF) mission will survey stars in our stellar neighborhood to search for planets and perform spectroscopic measurements to identify potential biomarkers in their atmospheres. TPF is currently planned for launch around 2015.

Johnson, Wyatt↗

NASA NTRS2004

Terrestrial Planet Finder : technology development plans and progress

Lindensmith, Chris↗

NASA NTRS2001

An interoperable data architecture for data exchange in a biomedical research network

This paper discusses the approach taken to develop a prototype data architecture for the discovery and validation of disease biomarkers within a biomedical research network.

data↗

NASA NTRS2018

Mission Concept for a Europa Lander

A NASA HQ-directed study team led by the Jet Propulsion Laboratory (JPL) with partners including Applied Physics Lab, Marshall Space Flight Center, Goddard Space Flight Center, Langley Research Center and Sandia National Laboratory has recently presented a mission concept for a Europa Lander that would search for bio-signatures and signs of life in the near-subsurface of the Jovian moon. The mission would follow the Europa Clipper multiple-flyby mission, planned for launch in June of 2022, which would provide reconnaissance imagery and other data to the Lander for use in selecting a scientifically compelling site and certifying it for engineering safety. The Europa Lander concept accommodates the Model Payload identified by the Europa Lander Science Definition Team (SDT) and documented in the Europa Lander Study 2016 Report released in February of 2017. The currently envisioned Europa Lander would launch on an SLS Block 1B as early as October of 2025 into a VEGA trajectory, arriving in the Jovian system as early as July of 2030. The baseline design of the integrated flight system includes a dedicated Carrier and Relay Stage, a Deorbit Vehicle composed of a Deorbit Stage consisting of a solid rocket motor (SRM), an MSL-like sky-crane Descent Stage, and a Lander which accommodates the instrument suite. The Lander would be powered by primary batteries over a 20-day surface mission. The science goals envisioned by the SDT require five samples taken from a depth of 10cm, a depth chosen to ensure minimal radiation processing of the potential biomarkers. Mission challenges include the large launch mass, unknown terrain topography, surface composition and materials properties, the high radiation environment, and complying with stringent planetary protection requirements. The mission concept uses a strategy of early risk reduction and overlapping requirements to provide robustness to harsh and uncertain environments. Early risk reduction efforts are aimed at maturing technologies associated with the sampling system, the intelligent landing system, high specific energy batteries, low mass and power motor controllers, and a thermal sterilization system.

Dooley, Jennifer↗

NASA NTRSDate not supplied

Chemical Reactivity of In-Situ Lunar Dust for Biotoxicity Assessment

Introduction: How does the chemical reactivity of in-situ lunar dust compare to Apollo samples currently stored in curation facilities here on Earth? Essential investigations of this question will help us to further mitigate exploration risks for future human explorers on the Moon and will also provide critical information for astrobiologists and space biologists using the Moon for scientific inquiry. Discussion: Apollo 14 dust biotoxicity studies, carried out by the NASA Lunar Airborne Dust Toxici-ty Assessment Group (LADTAG), included numerous physiochemical studies[1] and cellular and animal ex-periments. Intratracheal instillation [2] and inhalation studies [3] in rats both showed Apollo 14 dust to be intermediate in toxicity compared to low-tox titanium dusts and high-tox quartz dusts of similar particle siz-es. The collective results were used in models [4] to establish a safe exposure limit for astronauts [5]. Alt-hough LADTAG took extensive steps to preserve what chemical reactivity may still have existed in the sam-ples, it is simply unknown if they possessed true in-situ chemical reactivity or if that reactivity has de-cayed. Initial gas loss on collection and other altera-tions, and even intermittent exposure to Earth-normal conditions during subsequent decades of handling, obscure a forensic reconstruction of the initial state. Because a mineral dust’s chemical reactivity influ-ences its biotoxicity [6], researchers have developed methods to “activate” lunar dust and simulants [7][8]. Past studies that modeled impact processes and radia-tion [9] in the lunar environment suggest that in-situ lunar dust is likely to be more chemically reactive than Earth-exposed samples. Because of these results, in-situ measurements are warranted [10]. Other studies have examined the hydroxyl generating capability of iron bearing mineral phases [11][12] and further em-phasize the role iron plays in chemical reactivity of lunar material, as well as decay of chemical reactivity in mineral dusts [12]. Recent observations of the lunar surface reveal the presence of hematite [13], a finding that further supports the hypothesis that in-situ lunar dust is reactive. Since the lunar surface is heterogene-ous, dust biotoxicity is expected to vary from site to site [14] due to particle size, mineralogy, physical characteristics, degree of space weathering, and chemi-cal reactivity (Figure 1). This circumstance dictates dust assessments at a suite of lunar sites enabled by upcoming NASA and commercial lunar payload ser-vices (CLPS) opportunities. Dose, location, and dura-tion of particle exposure will also affect biological responses. In-situ chemical reactivity measurements can inform cross-cutting collaborative research cam-paigns such as astrobiology studies examining regolith interactions with organisms and its ability to preserve chemical and structural biomarkers, as well as space biology investigations that examine regolith-microbe interactions relating to life support systems, plant growth, biomining, and development of regolith bio-composites. Figure 1: Environment conditions on the lunar surface that may alter regolith reactivity. Summary A series of in-situ measurements of lu-nar dust free radical chemistry at future Artemis and CLPS landing sites, combined with LADTAG-like studies of freshly collected lunar dust specimens, will reveal the true chemical reactivity of in-situ lunar dust and generate scientific data that can be compared to the chemical reactivity and biotoxicity of samples from Apollo landing sites. Furthermore, results from in situ measurements and biotoxicity studies of freshly col-lected specimens can also be used to validate, or re-quire revision of, the current astronaut permissible exposure limit [15]. References: [1] McKay D et al (2015), Acta As-tronaut 107:163–176. [2] Rask J et al (2013), LPSC, p 3062. [3] Lam CW et al (2013), Inhal Toxicol 25:661–678. [4] James JT, et. al. (2013) , Inhal Toxicol 25:243–256. [5] Scully RR, et.al. (2013), Inhal Toxi-col 25:785–793. [6] Porter, D. W., et.al., (2002), Tox-icology 175, 63–71. [7] Wallace WT, et.al., (2009), Meteorit Planet Sci 44:961–970. [8] Wallace WT, et.al., (2010), Earth Planet Sci Lett 295:571–577. [9] Loftus D, Rask J, et.al., (2010), Earth Moon Planet 107:95–105. [10] Rask J, et.al., (2009) LEAG p 57. [11] Turci F, et.a., (2015), Astrobiology. 2015;15(5):371-380. [12] Hendrix DA, et.al., (2019), Geohealth. 2019;3(1):28-42. [13] Li, S., et.al., (2020), Science advances, 6(36), p.eaba1940. [14] Rask J. (2018), In: Cudnik B. (eds) Encyclopedia of Lunar Science. Springer, Cham. [15] Rask, J, (2020), LPI, Artemis III Sci. def. paper 2120.

chemical reactivity↗

NASA NTRSDate not supplied

MicroRNA Based Countermeasure Rescue Health Risks Associated with Space Radiation and Microgravity

From our earlier work, we demonstrated a circulating microRNA (miRNA) signature that is present and involved with the general increased health risks during spaceflight. From this work we demonstrated that this miRNA signature impacted the overall biology and health with both the microgravity and space radiation components of the space environment. We showed that this miRNA signature can be an optimal biomarker for health risk and also has potential to be utilized as a countermeasure to mitigate the damage caused by the space environment by utilizing a human 3D microvascular tissue model. By applying a novel self-delivery system to target 3 miRNAs (i.e. antagomirs) from our spaceflight miRNA signature impacting cardiovascular health risks, we were able to completely mitigate damage caused by exposure to simulated Galactic Cosmic Ray (GCR) irradiation. Here we further expand on the countermeasure experiments to uncover the specific novel biology involved with this countermeasure and in vivo experiments that demonstrates that these antagomirs rescue damage caused to certain organs due to both microgravity and space radiation. Specifically, the miRNAs rescued damage to the heart and immune suppression that occurred in addition to other key biology. In addition, we have also observed with the 3D microvascular tissue model improved DNA double strand break repair machinery which can also contribute to improved recovery and protection against damage caused by space radiation. This work expands on our previous work and further uncovers how a potential minimally invasive countermeasure can be used to mitigate space environment effects.

Angela Kubik↗

NASA NTRSDate not supplied

Overview of the Translational Radiation Research and Countermeasures (TRRaC) Project in Space Radiation

The Translational Radiation Research and Countermeasures (TRRaC) Project was initiated by the Space Radiation (SR) Element within NASA’s Human Research Program (HRP) to support the SR mission to understand and characterize the space radiation environment, understand and quantify radiation-associated risks, and mitigate the impacts of radiation-induced adverse health outcomes to enable human space exploration. TRRaC’s mission is to translate radiation research results from experimental studies and epidemiological data to humans and astronauts using bioinformatics and computational modeling. TRRaC will leverage existing datasets such as those available from NASA’s GeneLab repository and human medical radiation exposure registries, along with relevant data generated from ground-based research at molecular, cellular, tissue, and system levels, to: (1) refine the radiation dose rate effectiveness factor, (2) characterize radiation quality effects to improve estimates of the risk of exposure-induced death (REID) from space-relevant radiation exposures, and (3) identify pathways and biomarkers for cancer, cardiovascular disease, and central nervous system changes that are impacted by space radiation exposure.

Parastou Eslami↗

NASA NTRSDate not supplied

A MULTI TARGETED DIETARY SUPPLEMENT AS A POTENTIAL COUNTERMEASURE FOR DEEP SPACE EXPLORATION

Future deep space exploration to the Moon and Mars and beyond are currently major goals of NASA. Space flight presents unique challenges to the human physiology from the combined effects of microgravity, social isolation, altered circadian rhythm and radiation. Oxidative stress has been implicated as a crucial factor in space environment induced injury. Elucidating these detrimental effects on the central nervous system and brain is a primary objective, as they may result in adverse changes in astronaut behavior, mood and performance of critical tasks. We were recently funded by HRP Human Factors Behavioral Performance (HFBP) Element to test the hypothesis that Galactic Cosmic Ray Simulation (GCRsim) Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. Countermeasures to offset neurological damaged and cognitive deficits are paramount for protecting astronauts during deep space transits, but many countermeasures have been found to be unsuitable in ground-based model studies. We have developed a multi targeted dietary supplement (MTDS) designed to simultaneously ameliorate oxidative stress, inflammatory processes, energetic shortfalls, and membrane and mitochondrial deterioration. Administration of this MTDS has improved cognition and longevity in age accelerated and normal aging mice. Specifically, the MTDS was found to prevent a decline in mitochondrial complex III activity and cell loss, as well as prevent an increase in protein carbonyls and mitochondrial 3-nitrotyrosine in the brain of these mice. Further, administration of the MTDS was also found to reduce bone marrow chromosomal aberrations, DNA damage, lymphocyte apoptosis after whole body exposure of 2 Gy γ radiation. Mice exposed to a high dose cranially (10 Gy) had decreased cognitive responses (seen as increased latency time to uncover buried food and decreased novel object recognition), increased plasma 8-OHdG levels, increased markers of cell stress in the brain, decreased hippocampal brain-derived neurotrophic factor (BDNF) protein and decreased plasma levels of cytokines, all of which were ameliorated with treatment of the MTDS. As we have shown the supplement is protective in models of cognitive damage similar space environment stressors, particularly increased oxidative stress, we propose it may be a suitable countermeasure for upcoming deep space exploration.

Stephanie Puukila↗

NASA NTRSDate not supplied

B Complex 5-Methyltetrahydrofolate, Riboflavin, Pyridoxine, and Methylcobalamin Supplementation as a Non-Mechanical Countermeasure to Mitigate Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest

A subset of astronauts on International Space Station missions have experienced optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the precise cause of SANS is unknown, it is likely that there are multiple contributing factors, including genetic and environmental factors. Our recent work has shown that crewmembers with SANS have higher concentrations of metabolic biomarkers of impairments in the one-carbon metabolic pathway compared to unaffected astronauts - before, during, and after f light (1). B-vitamin status and the presence of one-carbon pathway single nucleotide polymorphism (SNP) variants predicted the incidence of SANS pathologies, including optic disc edema (2). Specifically, the G allele of methionine synthase reductase (MTRR) A66G and the C allele of serine hydroxymethyltransferase-1 (SHMT1) C1420T were associated with increased incidence of SANS pathologies (2). In a recent 30-d bed rest head-down tilt study with 0.5% CO2 exposure, 5 of 11 subjects developed optic disc edema (4) and the same SHMT1 C1420T and MTRR A66G genetic variants were associated with a larger increase in total retina thickness, a quantitative measure of optic disc edema (5). We published a multi-hit hypothesis of how genetics represents an indispensable element of SANS, which is a multifactorial problem (6). In brief: endothelial dysfunction secondary to genetic, biochemical/nutritional, and physiological (e.g., cardiovascular/fluid shift) f actors could lead to optic disc edema and the other ocular changes that occur in SANS. We expanded this hypothesis to include the possibility that genetic effects on B-vitamin status can alter nitric oxide synthesis and oxidative stress in the endothelium. This in turn could alter the turnover of structural components of the sclera, making it more susceptible to pathologic changes when faced with stressors related to the unrelenting headward fluid shift that occurs in weightlessness and strict head-down tilt bed rest (5). If the relationships that we have observed in flight and ground-based research hold true for the SANS Countermeasure Study, these genetic factors could predict who will be more susceptible to the development of SANS, and more importantly could also provide countermeasure options. As has been shown extensively in the literature, vitamin supplementation can serve to overcome genetic hindrances to one-carbon biochemistry and vascular physiology. Thus, based on our findings, publications, and hypotheses, supported by extensive supporting literature, we had hoped to test in the SANS Countermeasure Study the efficacy of a bioactive B-vitamin complex as a countermeasure to optimize function of the one-carbon pathway and prevent or mitigate optic disc edema during strict 6-degree head down tilt bed rest, and ultimately in space f light. While the supplement is no longer planned to be tested in the SANS Countermeasure Study because of laws regulating supplementation studies like this costing much more than initially planned, we will assess the contribution of one-carbon pathway genetics and B-vitamin status to SANS risk.

S R Zwart↗

NASA NTRSDate not supplied

Sensorimotor Predictors: Examining the Relationship Between Measures of Post-Landing Sensorimotor Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to Earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on sensorimotor functional tasks. To date, we have recruited fifteen astronauts who returned from the International Space Station on Soyuz and participated in sensorimotor field tests and/or posturography within one day following long-duration spaceflight. We are specifically utilizing a combination of three quantitative post-flight functional task outcomes(relative to pre-flight baselines): tandem walk, recovery from fall and dynamic posturography, along with a subjective self-rating of post-flight decrements and recovery. The recovery from fall is performed with eyes open on a stable support, allowing the use of vestibular, visual and proprioceptive feedback for task performance. In contrast, the dynamic posturography measures are performed with eyes closed on asway-referenced unstable support, requiring reliance on vestibular feedback for task performance. Tandem walk is performed on a stable surface with eyes open and eyes closed. Fourteen of the 15 subjects performed the field tests. These were nominally performed during three timepoints on the first postflight day, while posturography was performed only once during the third time point after direct return to JSC. More than 20% were unable to complete the initial field testing in the medical tent, while all participants completed testing during the third time point at JSC. As expected, there was considerable variability among all performance outcome measures, with more variability post-flight relative to preflight. Given the variability in all post-flight outcomes, we have been examining the relationships in performance across tasks. While there is a strong association within tests obtained at different landing daytime points, our preliminary findings suggest that by R+24 hrs performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. This underscores the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that further examining specific behavioral, neuroimaging and genetic sensorimotor biomarkers with post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

S J Wood↗

NASA NTRSDate not supplied

HUMAN FACTORS AND BEHAVIORAL PERFORMANCE EXPLORATION MEASURES: ASSESSING ASTRONAUT RISK

INTRODUCTION: The Human Factors and Behavioral Performance Exploration Measures (HFBP-EM) suite is a set of standardized measures to assess behavioral health and performance risk related to future exploration class missions, and to support reduction of the Human Research Program’s (HRP) Behavioral Medicine (BMed), Team, Sleep, and Human Systems Integration Architecture (HSIA) risks. This presentation will provide an overview of the HFBP-EM program, describe its implementation across spaceflight analogs and the international space station (ISS), and discuss its applicability to audience members. TOPIC: HFBP-EM is a research program designed to develop a standard set of measures that can be used in space and space-analog research to characterize BMed, Team, Sleep, and HSIA risks. It is an ongoing research project that is used examine the validity and reliability of HFBP measures, as well as their shorter forms. It also serves as a test bed for HFBP measures being considered for the spaceflight standard measures. The suite of measures is used to test the efficacy of countermeasures. To date, HFBP-EM has been collected in Human Exploration Research Analogs campaigns 4 and 5, and the SIRIUS 19 mission in the Russian Ground Based Experiment Complex. A subset of the HFBP-EM suite was collected during spaceflight as part of HRP’s Standard Measures in Spaceflight Project. Data was collected from a total of 55 multinational astronaut and astronaut-like crewmembers (mean age: 39.5, SD = 7.6; 31% female; 91% with advanced degrees). Three broad categories of HFBP-EM measures and their relevance to HRP risks will be discussed: 1) surveys that assess team functioning (Teams risk) as well as mood and affect (Bmed risk), 2) performance-based tasks of cognitive functioning and operationally relevant performance (Bmed risk), and 3) physiological biomarkers of sleep (sleep risk) and heart rate (Bmed risk). We will provide an overview of the background of the HFBP-EM program, what the suite currently includes, and next steps in its future development. We will also discuss the application to aerospace practitioners and researchers. APPLICATION: Astronaut teams selected for future space exploration missions will face several challenges that pose significant yet still unknown risks to the behavioral health and performance of astronauts. The HFBP-EM suite provides a comprehensive assessment of behavioral health and performance in space analog and spaceflight settings. This suite can be applied to both operational and research settings to advance risk reduction research for long duration space exploration missions.

S T Bell↗

NASA NTRSDate not supplied

Artificial Neural Networks to Predict Cognitive Impairment of Rodents Subjected to Space Radiation

INTRODUCTION We use artificial neural networks (ANNs) as an example machine learning (ML) tool to predict the cognitive performance impairment of rats induced by irradiation. The experimental data in the analyses is attentional set-shifting (ATSET) test scores from a rodent model exposed to ≤15 cGy of individual galactic cosmic radiation (GCR) ions: 4He, 28Si, or 56Fe, expected for a Lunar or Mars mission [1]. This work investigates rats at a subject-based level and uses applied dose and performance scores taken before irradiation to predict whether a rat will be impaired when irradiated. The results of this study are significant to crewed space missions as they support the potential of predicting an astronaut’s impairment in a specific task before spaceflight through the implementation of appropriately trained ML tools. METHODS Data used in this work are scores from the ATSET, a multi-stage constrained cognitive flexibility test [2]. Our computational model utilizes the number of attempts to reach the criterion to pass a stage as a behavioral performance measure for rats. We use the post-irradiation scores, generate thresholds from cumulative distribution plots of non-irradiated rats, and calculate the percent of irradiated rats whose scores fall below the threshold to infer how each radiation type/dose affects a population. Rats scoring above the threshold are labeled impaired while the others are non-impaired. We then employ ANNs as a typical ML technique, and use each subject’s individual scores taken before radiation along with the applied dose, to predict their personal susceptibility to cognitive impairment due to space radiation exposure. RESULTS AND CONCLUSION A significant finding is the exhibition of a dose-dependent increasing probability of impairment for 1 to 10 cGy of 28Si or 56Fe in the simple discrimination (SD) stage of the ATSET, and for 1 to 10 cGy of 56Fe in the compound discrimination (CD) stage. On a subject-based level, implementing ML classifiers such as ANNs identifies rats that have a higher tendency for impairment after GCR exposure [1]. The receiver operating characteristic (ROC) and the precision-recall (PR) curves of the ML models show a better prediction of impairment when 56Fe is the ion in question in both SD (Figure 1) and CD stages. They, however, do not depict impairment due to 4He in SD (Figure 1) and 28Si in CD, suggesting no dose-dependent impairment response in these cases. In this work, “good” prediction pertains to “better-than-random-chance”, due to the limited sample size and the high inter- and intra-individual variabilities in response to brain stimulation paradigms, as applicable to both animals and humans. More behavioral tests and biomarkers should be investigated on the same subjects, to be fed to the ML models to capture the agents responsible for performance alterations of some individuals versus others.

machine learning↗

NASA NTRSDate not supplied

Machine Learning Models to Predict Cognitive Impairment of Rodents Subjected to Space Radiation

machine learning↗

NASA NTRSDate not supplied

Sensorimotor Predictors: Examining the Relationship Between Measures of Post-Landing Sensorimotor Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to Earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on sensorimotor functional tasks. To date, we have recruited fifteen astronauts who returned from the International Space Station on Soyuz and participated in sensorimotor field tests and/or posturography within one day following long-duration spaceflight. We are specifically utilizing a combination of three quantitative post-flight functional task outcomes(relative to pre-flight baselines): tandem walk, recovery from fall and dynamic posturography, along with a subjective self-rating of post-flight decrements and recovery. The recovery from fall is performed with eyes open on a stable support, allowing the use of vestibular, visual and proprioceptive feedback for task performance. In contrast, the dynamic posturography measures are performed with eyes closed on asway-referenced unstable support, requiring reliance on vestibular feedback for task performance. Tandem walk is performed on a stable surface with eyes open and eyes closed. Fourteen of the 15 subjects performed the field tests. These were nominally performed during three timepoints on the first post flight day, while posturography was performed only once during the third time point after direct return to JSC. More than 20% were unable to complete the initial field testing in the medical tent, while all participants completed testing during the third time point at JSC. As expected, there was considerable variability among all performance outcome measures, with more variability post-flight relative to preflight. Given the variability in all post-flight outcomes, we have been examining the relationships in performance across tasks. While there is a strong association with in tests obtained at different landing daytime points, our preliminary findings suggest that by R+24 hrs performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. This underscores the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that further examining specific behavioral, neuroimaging and genetic sensorimotor biomarkers with post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

Yiri De Dios↗