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NASA NTRS2010

Managing the Risk for Early Onset Osteoporosis in Long-Duration Astronauts Due to Spaceflight

Early Onset Osteoporosis is probably the most recognized but poorly understood long-term health risk due to spaceflight. Osteoporosis management is primarily prophylactic and clinical interventions rely upon the ability to predict fractures which is currently determined by surrogate measures of bone strength. The RMAT for Early Onset Osteoporosis identified some open issues related to the fact that long-duration astronauts compose a unique group of subjects for which clinical approaches for osteoporosis management do not apply. Long-duration astronauts are healthy, young (25 to 55 years of age), predominantly male, and physical fit relative to the typical osteoporosis patient. Moreover, during prolonged space missions (typically 6-month missions) the skeleton not only adapts to weightlessness, but is influenced by numerous risk factors induced by operational constraints, e.g., inability to maintain preflight weight-bearing and aerobic activities, sub-optimal dietary intake (e.g., high sodium content for food stability, lack of fresh fruit and vegetables), suppression of vitamin D metabolism by uv shielding, and remote medicine care. Moreover, adaptation results in novel changes to astronauts bones that cannot be detected by current medically-useful measures. Consequently, a panel of clinicians (recognized leaders and policy-makers in osteoporosis) was convened to review the dataset of bone measures and bone loss risk factors in long-duration astronauts. Driven by the queries in the RMAT, the panel was charged to determine 1) if an intervention is required to prevent this risk, 2) what type and at what time would intervention be optimal, 3) what is the clinical trigger that would require a medical response from flight surgeons and 4) how should research data be used in the clinical care of astronauts. Hence, the RMAT determined that a bone health policy need to be formulated specific for this unique cohort subjected to a novel skeletal condition

Sibonga, Jean D.↗
NASA NTRS2010

Bone Density Following Three Years of Recovery from Long-Duration Space-Flight

Bone loss during long-duration space flight is well recognized, but the long-term implications on bone health following return from flight remain unclear. Among US crew who were involved in long-duration missions in space (Mir and ISS), we have previously shown that at approximately 12 months following return, men, but not women, had BMD values at most sites that were still lower than would be expected had they not been exposed to a prolonged period of microgravity. We now extend our observations to 3 years of follow-up post-flight. Using their age, pre-flight BMD and follow-up time, post-flight BMD values for each US crew were predicted based on the model developed from the community sample. We found BMD measures to be either stable or improve by 3 years relative to their immediate post-flight BMD, however only total hip BMD still remains significantly lower than would be expected had they not been exposed to microgravity. Among male US crew, who have had their BMD measured following at least 3 years of recovery post long-duration flight, they continue to have lower BMD at the hip than would be expected, raising potential concerns regarding future hip fracture risk.

Amin, S.↗
NASA NTRS2011

Full Mission Astronaut Radiation Exposure Assessments for Long Duration Lunar Surface Missions

Risk to astronauts due to ionizing radiation exposure is a primary concern for missions beyond Low Earth Orbit (LEO) and will drive mission architecture requirements, mission timelines, and operational practices. For short missions, radiation risk is dominated by the possibility of a large Solar Particle Event (SPE). Longer duration missions have both SPE and Galactic Cosmic Ray (GCR) risks. SPE exposure can contribute significantly toward cancer induction in combination with GCR. As mission duration increases, mitigation strategies must address the combined risks from SPE and GCR exposure. In this paper, full mission exposure assessments were performed for the proposed long duration lunar surface mission scenarios. In order to accomplish these assessments, previously developed radiation shielding models for a proposed lunar habitat and rover were utilized. End-to-End mission exposure assessments were performed by first calculating exposure rates for locations in the habitat, rover, and during Extra-Vehicular Activities (EVA). Subsequently, total mission exposures were evaluated for the proposed timelines. Mission exposure results, assessed in terms of effective dose, are presented for the proposed timelines and recommendations are made for improved astronaut shielding and safer operational practices.

Adamczyk, Anne↗
NASA NTRS2011

Increased Intracranial Pressure and Visual Impairment Associated with Long-Duration Spaceflight

Although humans have been flying in space since the 1960s, more recent missions have revealed a new suite of physiological adaptations and consequences of space flight. Notably, 60% of long-duration crewmembers (ISS/MIR) and >25% of short-duration (Shuttle) crewmembers have reported subjective degradation in vision (based on debrief comments) (Gibson 2011). Decreased near-visual acuity was demonstrated in 46% of ISS/Mir and 21% of Shuttle crewmembers, resulting in a shift of up to 1-2 diopters in their refractive correction. It is likely that the recently revealed ophthalmic changes have been present since the first days of human space flight, but have been overlooked or attributed to other causations. The reported changes in vision have occurred at various time points throughout missions, with ranging degrees of visual degradation. Although some cases resolved upon return to Earth, several astronauts have not regained preflight visual acuity, indicating that the damage may be permanent. While observing these changes over the years, without other overt symptomology and with the given age range of the flying population, this has largely been attributed to an expected hyperopic shift due to aging. However, the availability of onboard analysis techniques, including visual acuity assessments, retinal imagery, and ultrasounds of the eye and optic nerve tracts, along with more detailed post-flight techniques, has led to the recent recognition of a wider syndrome. Along with vision changes, findings include flattening of the globe, swelling of the optic disc (papilledema), choroidal folds in the retina, swelling of the optic nerve sheath, and visual field defects. It is widely hypothesized that this constellation of findings may be explained by an elevation of intracranial pressure (ICP). Out of the 60% of long-duration astronauts that have reported a subjective degradation in vision, a subset (currently 10 astronauts) have developed this syndrome. The National Aeronautics and Space Administration (NASA) has made it a high priority to understand this syndrome and provide mitigation techniques to protect crewmembers from visual impairment. While there are many possible factors that could contribute to intracranial hypertension associated with spaceflight, the relative contribution of these, as well as the processes by which eye damage occurs as a result of intracranial hypertension, are not fully understood. The observed pathophysiological phenomena are extremely complex and it is likely that multiple factors contribute to their incidence, rather than one simple mechanism. This paper will define and examine the findings in detail, and expound upon the potential contributing factors and their relative contribution to this syndrome.

Marshall-Bowman, Karina↗
NASA NTRS2011

Orthostatic Hypotension After Long-Duration Space Flight: NASA's Experiences from the International Space Station

Our laboratory previously reported that the incidence of orthostatic hypotension (OH) was greater after long- than short-duration spaceflight in astronauts who participated in Mir Space Station and Space Shuttle missions. To confirm and extend these findings, we retrospectively examined tilt test data from International Space Station (ISS) and Shuttle astronauts. We anticipated that the proportion of ISS astronauts experiencing OH would be high on landing day and the number of days to recover greater after long- than short-duration missions. Methods: Twenty ISS and 66 Shuttle astronauts participated in 10-min 80? head-up tilt tests 10 d before launch (L-10), on landing day (R+0) or 1 d after landing (R+1). Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. Many astronauts repeated the test 3 d (R+3) after landing. Fisher?s Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the tilt test on R+0. Cox regression was used to identify cardiovascular parameters that were associated with test completion across all tests, and mixed model analysis was used to compare the change and recovery rates between ISS and Shuttle astronauts. In these analyses, ISS data from R+0 and R+1 were pooled to provide sufficient statistical power. Results: The proportion of astronauts who completed the tilt test on R+0 without OH was less in ISS than in Shuttle astronauts (p=0.03). On R+0, only 2 of 6 ISS astronauts completed the test compared to 53 of 66 (80%) Shuttle astronauts. However, 8 of 9 ISS astronauts completed the test on R+1. On R+3, 13 of 15 (87%) of the ISS and 19 of 19 (100%) of the Shuttle astronauts completed the 10-min test. An index comprised of stroke volume and diastolic blood pressure provided a very good prediction of overall tilt survival. This index was altered by spaceflight similarly for both groups soon after landing (pooled R+0 and R+ 1), but ISS astronauts did not recover at the same rate as Shuttle astronauts (p=0.007). Conclusions: The proportion of ISS astronauts who could not complete the tilt test on R+0 due to OH (4 of 6) is similar to that reported in astronauts who flew on Mir (5 of 6). Further, cardiovascular parameters most closely associated with OH recover more slowly after long- compared to short-duration spaceflight.

Lee, Stuart M. C.↗
NASA NTRS2011

Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Future human space travel will primarily consist of long-duration missions aboard the International Space Station (ISS) or exploration class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage primarily from radiation, but also from psychological stress, reduced physical activity, diminished nutritional status, and, in the case of extravehicular activity, hyperoxic exposure. There is evidence that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this proposal is to identify biomarkers of oxidative and inflammatory stress and to correlate them to indices of atherosclerosis risk before, during, and after long-duration spaceflight. METHODS To meet the objectives of the study, we will study astronauts before, during, and up to 5 years after long-duration missions aboard ISS. Biomarkers of oxidative and inflammatory stress, some of which we have previously shown to be elevated with spaceflight, will be measured before, during, and after spaceflight. Arterial structure will be monitored using ultrasound to measure carotid intima-medial thickness before, during, and after weightlessness. Carotid intima-medial thickness has been shown to be a better indicator than Framingham Risk scores for prediction of atherosclerosis. Arterial function will be monitored using brachial flow-mediated dilation before flight and after landing. Brachial flow-mediated dilation is a good index of endothelium-dependent vasodilation, which is a sensitive predictor of atherosclerotic risk. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight and structural functional measures for up to 5 years after landing. EXPECTED RESULTS We hypothesize that these biomarkers of oxidative and inflammatory stress will be increased with spaceflight and will correlate with increased carotid intima-medial thickness in- and postflight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but that biomarkers of inflammatory stress and vascular indices of atherosclerosis risk will remain elevated.

Lee, Stuart M. C.↗
NASA NTRS2012

Acquisition of Long-Duration, Low-Gravity Slosh Data Utilizing Existing ISS Equipment (SPHERES) for Calibration of CFD Models of Coupled Fluid-Vehicle Behavior

Accurate prediction of coupled fluid slosh and launch vehicle or spacecraft dynamics (e.g., nutation/precessional movement about various axes, attitude changes, ect.) requires Computational Fluid Dynamics (CFD) models calibrated with low-gravity, long duration slosh data. Recently completed investigations of reduced gravity slosh behavior have demonstrated the limitations of utilizing parabolic flights on specialized aircraft with respect to the specific objectives of the experiments. Although valuable data was collected, the benefits of longer duration low-gravity environments were clearly established. The proposed research provides the first data set from long duration tests in zero gravity that can be directly used to benchmark CFD models, including the interaction between the sloshing fluid and the tank/vehicle dynamics. To explore the coupling of liquid slosh with the motion of an unconstrained tank in microgravity, NASA's Kennedy Space Center, Launch Services Program has teamed up with the Florida Institute of Technology (FIT), Massachusetts Institute of Technology (MIT) and the Office of the Chief Technologist (OCT) to perform a series of slosh dynamics experiments on the International Space Station using the SPHERES platform. The Synchronized Position Hold Engage Reorient Experimental Satellites (SPHERES) testbed provides a unique, free-floating instrumented platform on ISS that can be utilized in a manner that would solve many of the limitations of the current knowledge related to propellant slosh dynamics on launch vehicle and spacecraft fuel tanks. The six degree of freedom (6-DOF) motion of the SPHERES free-flyer is controlled by an array of cold-flow C02 thrusters, supplied from a built-in liquid C02 tank. These SPHERES can independently navigate and re-orient themselves within the ISS. The intent of this project is to design an externally mounted tank to be driven inside the ISS by a set of two SPHERES devices (Figure 1 ). The tank geometry simulates a launch vehicle upper stage propellant tank and the maneuvers replicate those of real vehicles. The design includes inertial sensors, data acquisition, image capture and data storage interfaces to the SPHERES VERTIGO computer system on board the flight article assembly. The design also includes mechanical and electronic interfaces to the existing SPHERES hardware, which include self-contained packages that can operate in conjunction with the existing SPHERES electronics.

Schallhorn, Paul↗
NASA NTRS2013

Acquisition of Long-Duration, Low-Gravity Slosh Data Utilizing Existing ISS Equipment (SPHERES) for Calibration of CFD Models of Coupled Fluid-Vehicle Behavior

Accurate prediction of coupled fluid slosh and launch vehicle or spacecraft dynamics (e.g., nutation/precessional movement about various axes, attitude changes, ect.) requires Computational Fluid Dynamics (CFD) models calibrated with low-gravity, long duration slosh data. Recently completed investigations of reduced gravity slosh behavior have demonstrated the limitations of utilizing parabolic flights on specialized aircraft with respect to the specific objectives of the experiments. Although valuable data was collected, the benefits of longer duration low-gravity environments were clearly established. The proposed research provides the first data set from long duration tests in zero gravity that can be directly used to benchmark CFD models, including the interaction between the sloshing fluid and the tank/vehicle dynamics. To explore the coupling of liquid slosh with the motion of an unconstrained tank in microgravity, NASA's Kennedy Space Center, Launch Services Program has teamed up with the Florida Institute of Technology (FIT), Massachusetts Institute of Technology (MIT) and the NASA Game Changing Development Program (GCD) to perform a series of slosh dynamics experiments on the International Space Station using the SPHERES platform. The Synchronized Position Hold Engage Reorient Experimental Satellites (SPHERES) testbed provides a unique, free-floating instrumented platform on ISS that can be utilized in a manner that would solve many of the limitations of the current knowledge related to propellant slosh dynamics on launch vehicle and spacecraft fuel tanks. The six degree of freedom (6-DOF) motion of the SPHERES free-flyer is controlled by an array of cold-flow C02 thrusters, supplied from a built-in liquid C02 tank. These SPHERES can independently navigate and re-orient themselves within the ISS. The intent of this project is to design an externally mounted tank to be driven inside the ISS by a set of two SPHERES devices (Figure 1). The tank geometry simulates a launch vehicle upper stage propellant tank and the maneuvers replicate those of real vehicles. The design includes inertial sensors, data acquisition, image capture and data storage interfaces to the SPHERES VERTIGO computer system on board the flight article assembly. The design also includes mechanical and electronic interfaces to the existing SPHERES hardware, which include self-contained packages that can operate in conjunction with the existing SPHERES electronics

Schallhorn, Paul↗
NASA NTRS2013

Plasma Cytokine Concentrations Indicate In-vivo Hormonal Regulation of Immunity is Altered During Long-Duration Spaceflight

Background: Aspects of immune system dysregulation associated with long‐duration spaceflight have yet to be fully characterized, and may represent a clinical risk to crewmembers during deep space missions. Plasma cytokine concentration may serve as an indicator of in vivo physiological changes or immune system mobilization. Methods: The plasma concentrations of 22 cytokines were monitored in 28 astronauts during long‐duration spaceflight onboard the International Space Station. Blood samples were collected three times before flight, 3‐5 times during flight (depending on mission duration), at landing and 30 days post‐landing. Analysis was performed by bead array immunoassay. Results: With few exceptions, minimal detectable mean plasma levels (<10 pg/ml) were observed at baseline (launch minus 180) for innate inflammatory cytokines or adaptive regulatory cytokines, however IL‐1ra and several chemokines were constitutively present. An increase in the plasma concentration IL‐8, IL‐1ra, Tpo, CCL4, CXCL5, TNF(alpha), GM‐CSF and VEGF was observed associated with spaceflight. Significant post‐flight increases were observed for IL‐6 and CCL2. No significant alterations were observed during or following spaceflight for adaptive/T‐regulatory cytokines (IL‐2, IFN(gamma), IL‐17, IL4, IL‐5, IL‐10). Conclusions: This pattern of cytokine dysregulation suggests multiple physiological adaptations persist during flight, including inflammation, leukocyte recruitment, angiogenesis and thrombocyte regulation.

Crician, Brian E.↗
NASA NTRS2014

Defining the Relationship between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts during and after Long-duration Spaceflight

Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and investigate if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight, and structural and functional measures for up to 5 years after landing. METHODS We will study 12 astronauts before, during, and up to 5 years after long-duration ISS missions. A panel of biomarkers of oxidative and inflammatory stress will be measured twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the postflight recovery phase (approx 3 days after landing). Arterial structure and vascular compliance will be measured at the same times and also at 1, 3, and 5 years after landing (surveillance). Arterial function will be measured using the same preflight, postflight, and surveillance schedule as arterial structure and vascular compliance measures, but will not be measured inflight. Biomarkers, some of which we have previously shown to be elevated with spaceflight, will be measured in venous blood samples and 24-h (in-flight) and 48-h (pre- and post-flight) urine pools. Arterial structure will be assessed from measures of carotid intima-media thickness, which have been shown to be better indicators of atherosclerotic than the Framingham Risk Score. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and is a sensitive predictor of atherosclerotic risk. Arterial pulse pressure measured in the brachial artery and stroke volume measured from cardiac ultrasound will be used to assess hemodynamic status, cardiac function, and systemic vascular compliance. Three astronauts are actively participating in the preflight data collection and training activities. One astronaut has completed all preflight activities and will participate in the first in-flight data collection sessions by the end of 2013. The first post-flight data collection sessions will occur in the spring of 2014. EXPECTED RESULTS We hypothesize that biomarkers of oxidative and inflammatory stress will increased with spaceflight and will correlate with increased carotid intima-media thickness during and after flight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but biomarkers of inflammatory stress and vascular indices of atherosclerotic risk will remain elevated.

Lee, Stuart M. C.↗
NASA NTRS2014

Improving Early Adaptation Following Long Duration Spaceflight by Enhancing Vestibular Information

Crewmember adapted to the microgravity state may need to egress the vehicle within a few minutes for safety and operational reasons after g-transitions. The transition from one sensorimotor state to another consists of two main mechanisms: strategic and plastic-adaptive and have been demonstrated in astronauts returning after long duration space flight. Strategic modifications represent "early adaptation" -immediate and transitory changes in control that are employed to deal with short-term changes in the environment. If these modifications are prolonged then plastic-adaptive changes are evoked that modify central nervous system function, automating new behavioral responses. More importantly, this longer term adaptive recovery mechanism was significantly associated with their strategic ability to recover on the first day after return to Earth G. We are developing a method based on stochastic resonance (SR) to enhance information transfer by improving the brain's ability to detect vestibular signals especially when combined with balance training exercises for rapid improvement in functional skill, for standing and mobility. The countermeasure to improve post-flight balance and locomotor disturbances is a stimulus delivery system that is wearable/portable providing low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system (stochastic vestibular stimulation, SVS). The techniques for improving signal detection using SVS may thus provide additional information to improve such strategic abilities and thus help in significantly reducing the number of days required to recover functional performance to preflight levels after long duration space flight. We have conducted a series of studies to document the efficacy of SVS stimulation on balance/locomotion tasks on unstable surfaces and motion tracking tasks during intra-vestibular system conflicts. In an initial study, we showed that SVS improved overall balance performance while standing on an unstable surface indicating that SVS may be sufficient to provide a comprehensive countermeasure approach for improving postural stability. In a second study, we showed that SVS improved locomotor performance on a treadmill mounted on an oscillating platform indicating that SVS may also be used to maximize locomotor performance during walking in unstable environments. In a third study, SVS was evaluated during an otolith-canal conflict scenario in a variable radius centrifuge at low frequency of oscillation (0.1 Hz) on both eye movements and perceptual responses (using a joystick) to track imposed oscillations. The variable radius centrifuge provides a selective tilting sensation that is detectable only by the otolith organs providing conflicting information from the canal organs of the vestibular system (intra-vestibular conflict). Results show that SVS significantly reduced the timing difference between both the eye movement responses as well as the perceptual tracking responses with respect to the imposed tilt sensations. These results indicate that SVS can improve performance in sensory conflict scenarios like that experienced during space flight. Such a SR countermeasure will act synergistically along with the pre-and in-flight adaptability training protocols providing an integrated, multi-disciplinary countermeasure capable of fulfilling multiple requirements making it a comprehensive and cost effective countermeasure approach to enhance sensorimotor capabilities following long-duration space flight.

Mulavara, Ajitkumar↗
NASA NTRS2014

Novel Exercise Hardware Requirements, Development, and Selection Process for Long-Duration Space Flight

Long-duration space flight poses many hazards to the health of the crew. Among those hazards is the physiological deconditioning of the musculoskeletal and cardiovascular systems due to prolonged exposure to microgravity. To combat the physical toll that exploration space flight may take on the crew, NASAs Human Research Program is charged with developing exercise protocols and hardware to maintain astronaut health and fitness during long-term missions. The goal of this effort is to preserve the physical capability of the crew to perform mission critical tasks in transit and during planetary surface operations. As NASA aims toward space travel outside of low-earth orbit (LEO), the constraints placed upon exercise equipment onboard the vehicle increase. Proposed vehicle architectures for transit to and from locations outside of LEO call for limits to equipment volume, mass, and power consumption. While NASA has made great strides in providing for the physical welfare of the crew, the equipment currently used onboard ISS is too large, too massive, and too power hungry to consider for long-duration flight. The goal of the Advanced Exercise Concepts (AEC) project is to maintain the resistive and aerobic capabilities of the current, ISS suite of exercise equipment, while making reductions in size, mass, and power consumption in order to make the equipment suitable for long-duration missions.

physical exercise↗
NASA NTRS2015

The Effects of Long Duration Bed Rest as a Spaceflight Analogue on Resting State Sensorimotor Network Functional Connectivity and Neurocognitive Performance

Long duration spaceflight has been associated with detrimental alterations in human sensorimotor systems and neurocognitive performance. Prolonged exposure to a head-down tilt position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with neurocognitive performance is largely unknown, but of potential importance to the health and performance of astronauts both during and post-flight. The aims of the present study are 1) to identify changes in sensorimotor resting state functional connectivity that occur with extended bed rest exposure, and to characterize their recovery time course; 2) to evaluate how these neural changes correlate with neurocognitive performance. Resting-state functional magnetic resonance imaging (rsfMRI) data were collected from 17 male participants. The data were acquired through the NASA bed rest facility, located at the University of Texas Medical Branch (Galveston, TX). Participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. RsfMRI data were obtained at seven time points: 7 and 12 days before bed rest; 7, 50, and 65 days during bed rest; and 7 and 12 days after bed rest. Functional connectivity magnetic resonance imaging (fcMRI) analysis was performed to measure the connectivity of sensorimotor networks in the brain before, during, and post-bed rest. We found a decrease in left putamen connectivity with the pre- and post-central gyri from pre bed rest to the last day in bed rest. In addition, vestibular cortex connectivity with the posterior cingulate cortex decreased from pre to post bed rest. Furthermore, connectivity between cerebellar right superior posterior fissure and other cerebellar regions decreased from pre bed rest to the last day in bed rest. In contrast, connectivity within the default mode network remained stable over the course of bed rest. We also utilized a battery of behavioral measures including spatial working memory tasks and measures of functional mobility and balance. These behavioral measurements were collected before, during, and after bed rest. We will report the preliminary findings of correlations observed between brain functional connectivity and behavioral performance changes. Our results suggest that sensorimotor brain networks exhibit decoupling with extended periods of reduced usage. The findings from this study could aid in the understanding and future design of targeted countermeasures to alleviate the detrimental health and neurocognitive effects of long-duration spaceflight.

Cassady, K.↗
NASA NTRS2015

NASA's Rodent Research Project: Validation of Capabilities for Conducting Long Duration Experiments in Space

Research using rodents is an essential tool for advancing biomedical research on Earth and in space. Prior rodent experiments on the Shuttle were limited by the short flight duration. The International Space Station (ISS) provides a new platform for conducting rodent experiments under long duration conditions. Rodent Research (RR)-1 was conducted to validate flight hardware, operations, and science capabilities that were developed at the NASA Ames Research Center. Twenty C57BL6J adult female mice were launched on Sept 21, 2014 in a Dragon Capsule (SpaceX-4), then transferred to the ISS for a total time of 21-22 days (10 commercial mice) or 37 days (10 validation mice). Tissues collected on-orbit were either rapidly frozen or preserved in RNAlater at -80C (n2group) until their return to Earth. Remaining carcasses on-orbit were rapidly frozen for dissection post-flight. The three controls groups at Kennedy Space Center consisted of: Basal mice euthanized at the time of launch, Vivarium controls housed in standard cages, and Ground Controls (GC) housed in flight hardware within an environmental chamber. Upon return to Earth, there were no differences in body weights between Flight (FLT) and GC at the end of the 37 days in space. Liver enzyme activity levels of FLT mice and all control mice were similar in magnitude to those of the samples that were processed under optimal conditions in the laboratory. Liver samples dissected on-orbit yielded high quality RNA (RIN8.99+-0.59, n7). Liver samples dissected post-flight from the intact, frozen FLT carcasses yielded RIN of 7.27 +- 0.52 (n6). Additionally, wet weights of various tissues were measured. Adrenal glands and spleen showed no significant differences in FLT compared to GC although thymus and livers weights were significantly greater in FLT compared to GC. Over 3,000 tissue aliquots collected post-flight from the four groups of mice were deposited into the Ames Life Science Data Archives for future Biospecimen Sharing Program. Together, the RR validation flight successfully demonstrates the capability to support long-duration experimentation on the ISS to achieve both basic science and biomedical objectives.

spaceflight↗
NASA NTRS2016

The Effects of Long Duration Bed Rest on Brain Functional Connectivity and Sensorimotor Functioning

Long duration spaceflight has been associated with detrimental alterations in human sensorimotor functioning. Prolonged exposure to a head-down tilt (HDT) position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with behavior is largely unknown, but of importance to the health and performance of astronauts both during and post-flight. In the present study, we investigate the effects of prolonged exposure to HDT bed rest on resting state brain functional connectivity and its association with behavioral changes in 17 male participants. To validate that our findings were not due to confounding factors such as time or task practice, we also acquired resting state functional magnetic resonance imaging (rs-fMRI) and behavioral measurements from 14 normative control participants at four time points. Bed rest participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. Rs-fMRI and behavioral data were obtained at seven time points averaging around: 12 and 8 days prior to bed rest; 7, 50, and 70 days during bed rest; and 8 and 12 days after bed rest. 70 days of HDT bed rest resulted in significant increases in functional connectivity during bed rest followed by a reversal of changes in the post bed rest recovery period between motor cortical and somatosensory areas of the brain. In contrast, decreases in connectivity were observed between temporoparietal regions. Furthermore, post-hoc correlation analyses revealed a significant relationship between motor-somatosensory network connectivity and standing balance performance changes; participants that exhibited the greatest increases in connectivity strength showed the least deterioration in postural equilibrium with HDT bed rest. This suggests that neuroplastic processes may facilitate adaptation to the HDT bed rest environment. The findings from this study provide novel insights into the neurobiology and future risk assessments of long-duration spaceflight.

Cassady, K.↗
NASA NTRS2015

Evolvable Mars Campaign Long Duration Habitation Strategies: Architectural Approaches to Enable Human Exploration Missions

The Evolvable Mars Campaign (EMC) is the current NASA Mars mission planning effort which seeks to establish sustainable, realistic strategies to enable crewed Mars missions in the mid-2030s timeframe. The primary outcome of the Evolvable Mars Campaign is not to produce "The Plan" for sending humans to Mars, but instead its intent is to inform the Human Exploration and Operations Mission Directorate near-term key decisions and investment priorities to prepare for those types of missions. The FY'15 EMC effort focused upon analysis of integrated mission architectures to identify technically appealing transportation strategies, logistics build-up strategies, and vehicle designs for reaching and exploring Mars moons and Mars surface. As part of the development of this campaign, long duration habitats are required which are capable of supporting crew with limited resupply and crew abort during the Mars transit, Mars moons, and Mars surface segments of EMC missions. In particular, the EMC design team sought to design a single, affordable habitation system whose manufactured units could be outfitted uniquely for each of these missions and reused for multiple crewed missions. This habitat system must provide all of the functionality to safely support 4 crew for long durations while meeting mass and volume constraints for each of the mission segments set by the chosen transportation architecture and propulsion technologies. This paper describes several proposed long-duration habitation strategies to enable the Evolvable Mars Campaign through improvements in mass, cost, and reusability, and presents results of analysis to compare the options and identify promising solutions. The concepts investigated include several monolithic concepts: monolithic clean sheet designs, and concepts which leverage the co-manifested payload capability of NASA's Space Launch System (SLS) to deliver habitable elements within the Universal Payload Adaptor between the SLS upper stage and the Orion/Service module on the top of the vehicle. Multiple modular habitat options for Mars surface and in-space missions are also considered with various functionality and volume splits between modules to find the best balance of reducing the single largest mass which must be delivered to a destination and reducing the number of separate elements which must be launched. Analysis results presented for each of these concepts in this paper include mass/volume/power sizing using parametric sizing tools, identification of unique operational constraints, and limited comments on the additional impacts of reusability/dormancy on system design. Finally, recommendations will be made for promising solutions which will be carried forward for consideration in the Evolvable Mars Campaign work.

Simon, Matthew A.↗
NASA NTRS2016

Field Test: Results of Tandem Walk Performance Following Long-Duration Spaceflight

BACKGROUND: Coordinated locomotion has proven to be challenging for many astronauts following long duration spaceflight. As NASA's vision for spaceflight points toward interplanetary travel, we must prepare for unassisted landings, where crewmembers may need to perform mission critical tasks within minutes of landing. Thus, it is vital to develop a knowledge base from which operational guidelines can be written that define when astronauts can be expected to safely perform certain tasks. Data obtained during the Field Test experiment (FT) will add important insight to this knowledge base. Specifically, we aim to develop a recovery timeline of functional sensorimotor performance during the first 24 hours and several days after landing. METHODS: FT is an ongoing study of 30 long-duration ISS crewmembers. Thus far, 9 have completed the full FT (5 U.S. Orbital Segment [USOS] astronauts and 4 Russian cosmonauts) and 4 more consented and launching within the next year. This is in addition to the eighteen crewmembers that participated in the pilot FT (11 USOS and 7 Russian crewmembers). The FT is conducted three times preflight and three times during the first 24 hours after landing. All crewmembers were tested in Kazakhstan in either the medical tent at the Soyuz landing site (~one hour post-landing), or at the airport (~four hours post-landing). The USOS crewmembers were also tested at the refueling stop (~12 hours post-landing) and at the NASA Johnson Space Center (~24 hours post-landing) and a final session 7 days post-landing. Crewmembers are instrumented with 9 inertial measurement unit sensors that measure acceleration and angular displacement (APDM's Emerald Sensors) and foot pressure-sensing insoles that measure force, acceleration, and center of pressure (Moticon GmbH, Munich, Germany) along with heart rate and blood pressure recording instrumentation. The FT consists of 12 tasks, but here we will focus on the most challenging task, the Tandem Walk, which was also performed as part of pilot FT. To perform the Tandem Walk, subjects begin with their feet together, their arms crossed at their chest and eyes closed. When ready, they brought one foot forward and touched the heel of their foot to their toe, repeating with the other foot, and continuing for about 10 steps. Three trials were collected with the eyes closed and a fourth trial was collected with eyes open. There are four metrics which are used to determine the performance level of the Tandem Walk. The first is percent correct steps. For a step to be counted as correct, the foot could not touch the ground while bringing it forward (no side stepping), eyes must stay closed during the eyes closed trials, the heel and toe should be touching, or almost touching (no large gaps) and there shouldn't be more than a three second pause between steps. Three judges score each step and the median of the three scores is kept. The second metric is the average step speed, or the number of steps/time to complete them. Thirdly, the root mean squared (RMS) error in the resultant trunk acceleration is used to determine the amount of upper body instability observed during the task. Finally, the RMS error of the mediolateral center of pressure as measured by the Moticon insoles is used to determine the mediolateral instability at the foot level. These four parameters are combined into a new overall Tandem Walk Parameter. RESULTS: Preliminary results show that crewmembers perform the Tandem Walk significantly worse the first 24 hours after landing as compared to their baseline performance. We find that each of the four performance metrics is significantly worse immediately after landing. We will present the results of tandem walk performance during the FT thus far. We will also combine these with the 18 crewmembers that participated in the pilot FT, concentrating on the level of performance and recovery rate. CONCLUSION: The Tandem Walk data collected as part of the FT experiment will provide invaluable information on the performance capabilities of astronauts during the first 24 hours after returning from long-duration spaceflight that can be used in planning future Mars, or other deep-space missions with unassisted landings. FT will determine the average sensorimotor recovery timeline and inform return-to-duty guidelines for unassisted landings.

Rosenberg, M. J. F.↗
NASA NTRS2015

NASA's Rodent Research Project on ISS: Validation of a New Platform for Conducting Biomedical and Basic Research into the Consequences of Long Duration Habitation in Space

Rodent research has played a key role in advancing biomedical discoveries both on Earth and in space. The National Research Counsel’s Decadal survey(1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA ARC to support both commercial and government-sponsored rodent research.Rodent Research-1 (RR-1) was the first mission in which animals were delivered and maintained in the ISS for a long duration mission in modified Animal Enclosure Module hardware. Both RR validation and commercial science objectives were pursued on the RR-1 mission. Adult female mice (20 total Flight, FLT) were launched Sept 21, 2014 in RR hardware within a Dragon Capsule (SpaceX4), then after 4 days in transit, were transferred for habitation on the ISS for 17 days (commercial) or 33 days (validation), when animals were euthanized and select tissues recovered on orbit. Various controls groups consisted of: 1) Basal mice from the same cohorts as FLT mice, but tissues were recovered at time of launch, 2) Vivarium (VIV) were housed in standard cages 3) Ground Controls (GC) were housed in flight hardware within an environmental chamber at Kennedy Space Center. The health and behavior of all mice on the ISS were monitored by video feed on a daily basis. Mice were euthanized by injection of Euthasol, then either fast frozen intact or dissected to preserve livers (fast frozen) and spleens (RNAlater). Samples were stored at ≤ -80˚C until their return to Earth for later analyses.Hardware performed nominally throughout the mission and the planned in-flight science operations were completed successfully. FLT mice appeared generally more physically active on orbit than respective GC groups. After 33 days on the ISS, mean body weights of FLT mice did not differ from GC, with both groups showing a 6% rise compared to time of launch, while VIV mice showed an 8% rise over the same period. Importantly, there were no significant differences in body weights between groups at the end of 33 days on the ISS, providing an indication that the RR hardware supported the health of the mice both on Earth and in space. Based on the preliminary data obtained from the livers and spleens of mice after 17 days on the ISS, purified RNA was of high quality (RIN values of spleen: FLT=9.48 +0.40, GC=9.28 +0.44, n=5/group); therefore, RNA quality from samples retrieved on orbit was acceptable for even the most demanding transcriptomic analyses. In addition, liver enzyme activity levels (units/mg protein) of FLT mice (after 17d on ISS) and all control mice were similar in magnitude to samples that were optimally prepared by freezing in liquid nitrogen in the laboratory (enzymes analyzed included catalase, glutathione reductase and glyceraldehyde-3-phosphate dehydrogenase). Validation analyses still in progress include behavior and tissue biochemistries, as well as optimization of science return by post-flight recovery of tissues for biospecimen sharing and global expression analyses.Together, these preliminary findings demonstrate new capability for supporting long duration rodent research on the ISS to achieve both basic science and biomedical objectives.

Globus, R. K.↗