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Building a Shared Definitional Model of Long Duration Human Spaceflight

Objective: To establish the need for a shared definitional model of long duration human spaceflight, that would provide a framework and vision to facilitate communication, research and practice In 1956, on the eve of human space travel, Hubertus Strughold first proposed a "simple classification of the present and future stages of manned flight" that identified key factors, risks and developmental stages for the evolutionary journey ahead. As we look to new destinations, we need a current shared working definitional model of long duration human space flight to help guide our path. Here we describe our preliminary findings and outline potential approaches for the future development of a definition and broader classification system

Arias, Diana↗

SPACEFLIGHT ASSOCIATED NEURO-OCULAR SYNDROME (SANS): 2023 CLINICAL UPDATE

INTRODUCTION Spaceflight Associated Neuro-ocular Syndrome (SANS) is a condition unique to long-duration spaceflight, with an unclear pathogenesis and pathophysiology, and no perfect terrestrial analog. Approximately 66% of long duration spaceflight (LDSF) astronauts present with the earliest indication of SANS, which is defined as development of any of the following signs in at least one eye during or immediately following spaceflight: 1) optic disc edema (ODE; represented by an increase of ≥ 20 microns in peripapillary total retinal thickness [ΔTRT]); 2) chorioretinal folds; 3) globe flattening; and 4) excessive shift in refractive error (≥ +0.75D). Each of these signs presents potential risk to a crewmember’s vision and mission effectiveness, with ODE posing the highest risk overall. It is not yet known what severity and/or duration of these signs might lead to acute or permanent impacts to ocular anatomy or visual performance. Brain anatomical changes also occur during long-duration spaceflight and are being monitored in the astronaut population; however, these changes have not yet been associated with functional decrements or with SANS. An update will be provided on the latest SANS clinical analyses, diagnostics, and program initiatives. METHODS Data were obtained from clinical records and SANS subject matter experts (SMEs) to compile a SANS clinical update. Areas of interest include: 1) prevalence of SANS signs, 2) defining clinical thresholds for SANS, and 3) an overview of current and planned SANS clinical efforts. DISCUSSION SANS Sign Prevalence: Analysis at the time of this abstract submission indicates that the approximate prevalence of primary SANS findings in USOS LDSF crewmembers is: 64% for ODE (≥ 20-micron ΔTRT), 15% for chorioretinal folds, 26% for globe flattening, and 14% for hyperopic shifts in refractive error (≥ +0.75D). Clinical Thresholds:  The Earliest Indication of SANS was presented publicly for the first time at the 2020 NASA Human Research Program Investigators’ Workshop. See definition in Introduction section (above).  Clinically Concerning SANS – Development of any of the following signs during or immediately following spaceflight: 1) ODE (≥ 55-micron ΔTRT* and/or Frisèn grade ≥1*), 2) sharp chorioretinal folds in the vicinity of the macula, or 3) moderate globe flattening.  Pathological SANS with an Acute Functional Impact – Development of any of the following signs/symptoms during or immediately following spaceflight: 1) visual field loss (e.g., enlarged blindspot), 2) distorted centralvision, or 3) shift in refractive error beyond power of available correction (e.g., “space anticipation glasses”).  Pathological SANS affecting Long-Term Health – Development of any of the following signs/symptoms during or following spaceflight: 1) permanent visual field loss, 2) reduced retinal nerve fiber layer (RNFL) thickness, 3) permanently distorted central vision, 4) atrophy of retinal pigment epithelium (RPE) or photoreceptors, or 5) choroidal neovascularization. Current & Planned Clinical Efforts (accurate at time of abstract submission): All SANS diagnostic hardware are performing nominally onboard the International Space Station: vision screening, fundoscope, optical coherence tomography (OCT) device, ultrasound, and tonometer. The Goggle-Based Visual Field (GBVF) device is nearing completion of its clinical validation study at Ohio State University and is planned for parabolic flight testing in fiscal year 2023 (FY23); pending positive results, this sequence may pave the way towards an ISS technology demonstration in FY24.

T J Brunstetter↗

DEVELOPMENT OF AN INFLIGHT COUNTERMEASURE TO MITIGATE POSTFLIGHT GAIT DYSFUNCTION

Following spaceflight crewmembers experience gait and postural instabilities due to inflight adaptive alterations in sensorimotor function. These changes can pose a risk to crew safety if nominal or emergency vehicle egress is required immediately following long-duration spaceflight. At present, no operational countermeasure is available to mitigate postflight locomotor disturbances. Therefore, the goal of this study is to develop an inflight training regimen that facilitates the recovery of locomotor function after long-duration spaceflight. The countermeasure we are developing is based on the concept of variable practice. During this type of training the subject gains experience producing the appropriate adaptive motor behavior under a variety of sensory conditions and response constraints. This countermeasure is built around current ISS treadmill exercise activities. Crewmembers will conduct their nominal inflight treadmill exercise while being exposed to variations in visual flow patterns. These variations will challenge the postural and locomotor systems repeatedly, thereby promoting adaptive reorganization in locomotor behavior. As a result of this training a subject learns to solve a class of motor problems, rather than a specific motor solution to one problem, Le., the subject learns response generalizability or the ability to "learn to learn" under a variety of environmental constraints. We anticipate that this training will accelerate recovery of postural and locomotor function during readaptation to gravitational environments following spaceflight facilitating neural adaptation to unit (Earth) and partial (Mars) gravity after long-duration spaceflight. The study calls for one group of subjects to perform the inflight treadmill training regimen while a control group of subjects performs only the nominal exercise procedures. Locomotor function in both groups is assessed before and after spaceflight using two tests of gait function: The Integrated Treadmill Locomotion Test (ITLT) and the Functional Mobility Test (FMT). The ITLT characterizes alterations in the integrated function of multiple sensorimotor subsystems responsible for the control of locomotion. This test calls for subjects to walk on a motorized treadmill while we assess changes in dynamic postural stability, head-trunk coordination, short-latency head stabilization responses, dynamic visual acuity, lower limb coordination strategies and gait cycle timing. To make these assessments we measure the following parameters while subjects walk on the treadmill: 1) full body 3-dimensional kinematics using a motion capture system (Motion Analysis Corp., Santa Rosa, CA); 2) the shock-wave transmitted from heel-strike to the head using triaxial accelerometers placed on the tibia and head (Entran, Fairfield, NJ); 3) vertical forces using an instrumented treadmill (Kistler Instrument Corp., Amherst, NY); 4) Dynamic visual acuity using Landolt Cs presented on a laptop computer located 4m from the eyes and 5) Gait cycle timing using foot-switches (Motion Lab Systems, Inc., Baton Rouge, LA) attached to the plantar surface of each shoe at the heel and toe. The FMT evaluates a subject's ability to perform challenging locomotor maneuvers similar to those encountered during an egress from a space vehicle. Subjects step over and duck under obstacles along with negotiating a series of pylons set up on a base of 10 cm thick medium density foam. The dependent measures for the FMT are time to complete the course and the number of obstacles touched. To date, we have collected pre and postflight locomotion data from Expeditions 5-9 who will serve as part of the control group for this study. Preliminary results comparing the recovery rates in gait control sub-systems obtained from the ITLT and FMT performance showed two recovery patterns: 1) a concordant recovery trend between gait control parameters and FMT performance indicating a restitution pattern of recovery and 2) gait controecovery that lagged recovery in FMT performance suggesting that improvement in locomotor function was attained through a pattern of substitution. These data suggest that recovery of postflight locomotor function may occur through adaptive mechanisms that lead to either restitution or substitution of function. Understanding the modes of postflight readaptation has implications for countermeasure development and testing and in astronaut postflight rehabilitation.

Bloomberg, J. J.↗

Development of an Inflight Countermeasure to Mitigate Postflight Gait Dysfunction

Following spaceflight crewmembers experience gait and postural instabilities due to inflight adaptive alterations in sensorimotor function. These changes can pose a risk to crew safety if nominal or emergency vehicle egress is required immediately following long-duration spaceflight. At present, no operational countermeasure is available to mitigate postflight locomotor disturbances. Therefore, the goal of this study is to develop an inflight training regimen that facilitates the recovery of locomotor function after long-duration spaceflight. The countermeasure we are developing is based on the concept of variable practice. During this type of training the subject gains experience producing the appropriate adaptive motor behavior under a variety of sensory conditions and response constraints. This countermeasure is built around current ISS treadmill exercise activities. Crewmembers will conduct their nominal inflight treadmill exercise while being exposed to variations in visual flow patterns. These variations will challenge the postural and locomotor systems repeatedly, thereby promoting adaptive reorganization in locomotor behavior. As a result of this training a subject learns to solve a class of motor problems, rather than a specific motor solution to one problem, Le., the subject learns response generalizability or the ability to "learn to learn" under a variety of environmental constraints. We anticipate that this training will accelerate recovery of postural and locomotor function during readaptation to gravitational environments following spaceflight facilitating neural adaptation to unit (Earth) and partial (Mars) gravity after long-duration spaceflight. The study calls for one group of subjects to perform the inflight treadmill training regimen while a control group of subjects performs only the nominal exercise procedures. Locomotor function in both groups is assessed before and after spaceflight using two tests of gait function: The Integrated Treadmill Locomotion Test (ITLT) and the Functional Mobility Test (FMT). The ITLT characterizes alterations in the integrated function of multiple sensorimotor subsystems responsible for the control of locomotion. This test calls for subjects to walk on a motorized treadmill while we assess changes in dynamic postural stability, head-trunk coordination, short-latency head stabilization responses, dynamic visual acuity, lower limb coordination strategies and gait cycle timing. To make these assessments we measure the following parameters while subjects walk on the treadmill: 1) full body 3-dimensional kinematics using a motion capture system (Motion Analysis Corp., Santa Rosa, CA); 2) the shock-wave transmitted from heel-strike to the head using triaxial accelerometers placed on the tibia and head (Entran, Fairfield, NJ); 3) vertical forces using an instumented treadmill (Kistler Instrument Corp., Amherst, NY); 4) Dynamic visual acuity using Landolt Cs presented on a laptop computer located 4m from the eyes and 5) Gait cycle timing using foot-switches (Motion Lab Systems, Inc., Baton Rouge, LA) attached to the plantar surface of each shoe at the heel and toe. The FMT evaluates s. subject's ability to perform challenging locomotor maneuvers similar to those encountered during an egress from a space vehicle. Subjects step over and duck under obstacles along with negotiating a series of pylons set up on a base of 10 cm thick medium density foam. The dependent measures for the FMT are time to complete the course and the number of obstacles touched. To date, we have collected pre and postflight locomotion data from Expeditions 5-9 who will serve as part of the control group for this study. Preliminary results comparing the recovery rates in gait control sub-systems obtained from the ITLT and FMT performance showed two recovery patterns: 1) a concordant recovery trend between gait control parameters and FMT performance indicating a restitution pattern of recovery and 2) gait controecovery that lagged recovery in FMT performance suggesting that improvement in locomotor function was attained through a pattern of substitution. These data suggest that recovery of postflight locomotor function may occur through adaptive mechanisms that lead to either restitution or substitution of function. Understanding the modes of postflight readaptation has implications for countermeasure development and testing and in astronaut postflight rehabilitation.

Bloomberg, J. J.↗

Adaptive Effects on Locomotion Performance Following Exposure to a Rotating Virtual Environment

During long-duration spaceflight, astronauts experience alterations in vestibular and somatosensory cues that result in adaptive disturbances in balance and coordination upon return to Earth. These changes can pose a risk to crew safety and to mission objectives if nominal or emergency vehicle egress is required immediately following long-duration spaceflight. At present, no operational countermeasure is available to mitigate the adaptive sensorimotor component underlying the locomotor disturbances that occur after spaceflight. Therefore, the goal of this study is to develop an inflight training regimen that facilitates recovery of locomotor function after long-duration spaceflight. The countermeasure we are proposing is based on the concept of adaptive generalization. During this type of training the subject gains experience producing the appropriate adaptive motor behavior under a variety of sensory conditions and response constraints. As a result of this training a subject learns to solve a class of motor problems, rather than a specific motor solution to one problem, i.e., the subject learns response generalizability or the ability to "learn to learn." under a variety of environmental constraints. We are developing an inflight countermeasure built around treadmill exercise activities. By manipulating the sensory conditions of exercise by varying visual flow patterns, body load and speed we will systematically and repeatedly promote adaptive change in locomotor behavior. It has been shown that variable practice training increases adaptability to novel visuo-motor situations. While walking over ground in a stereoscopic virtual environment that oscillated in roll, subjects have shown compensatory torso rotation in the direction of scene rotation that resulted in positional variation away from a desired linear path. Thus, postural sway and locomotor stability in 1-g can be modulated by visual flow patterns and used during inflight treadmill training to promote adaptive generalization. The purpose of this study was to determine if adaptive modification in locomotor performance could be achieved by viewing simulated self-motion in a passive-immersive virtual ' environment over a prolonged period during treadmill locomotion.

Mulavara, A. P.↗

Microgreens for Human Nutrition in Spaceflight

For long-duration spaceflight missions, providing adequate nutritional needs of the crew is a documented risk. This can be mitigated with dietary supplementation of nutrient-dense young vegetables including microgreens. Why microgreens? Traditional crops can take months to mature, but microgreens are ready to harvest in within two weeks, and they can be grown in small volumes. This rapid turn-around time makes them practical for any spaceflight scenario where crew time is limited, or when power, mass, and volume limitations prevent growing crops to maturity. In this literature review we will introduce microgreens that have been screened by the USDA for nutritional content, and discuss their nutritional benefits in relation to the specific needs of astronauts, as defined by the NASA Human Research Program. We will specifically highlight the benefits of iron, magnesium, potassium, and carotenoids. We also discuss potential lighting and fertilizer regimens that could be used to further improve nutrient content of microgreens grown in microgravity. Developing microgreens for spaceflight will give us access to crops that are specifically designed to meet crew nutritional needs for future exploration missions.

Johnson, C. M.↗

Contamination Mitigation Strategies for Long Duration Human Spaceflight Missions

Contamination control issues are particularly challenging for long-term human spaceflight and are associated with the search for life, dynamic environmental conditions, human-robotic-environment interaction, sample collection and return, biological processes, waste management, long-term environmental disturbance, etc. These issues impact mission success, human health, planetary protection, and research and discovery. Mitigation and control techniques and strategies may include and integrate long-term environmental monitoring and reporting, contamination control and planetary protection protocols, habitation site design, habitat design, and surface exploration and traverse pathways and area access planning.

enviroment↗

Relationships Among Lower Body Strength, Power, and Performance of Functional Tasks

There is a large degree of variability among crewmembers with respect to decrements in muscle strength and power following long duration spaceflight, ranging from 0 to approx.30% reductions. The purpose of this study was to investigate the influence of varying decrements in lower body muscle strength and power (relative to body weight) on the performance of 2 occupationally relevant tasks (ladder climb and supine egress & walk). Seventeen participants with leg strength similar to US crewmembers performed a leg press power test, an isokinetic knee extension strength test and they were asked to complete the 2 functional tasks as quickly as possible. On additional test days the participants were asked to repeat the functional tasks under 3 conditions where a different external load was applied each time using a weighted suit in order to experimentally manipulate participants strength/body weight and power/body weight ratios. The weight in the suit ranged from 20-120% of body weight and was distributed in proportion to limb segment weights to minimize changes in center of gravity. The ladder task consisted of climbing 40 rungs on a ladder treadmill as fast as possible. The supine egress & walk task consisted of rising from a supine position and walking through an obstacle course. Results show a relatively linear relationship between strength/body weight and task time and power/body weight with task time such that the fastest performance times are associated with higher strength and power with about half the variance in task time is accounted for by a single variable (either strength or power). For the average person, a 20% reduction in power/body weight (from 18 to 14.4 W/kg) induces an increase (slowing) of about 10 seconds in the ladder climb task from 14 to 24 seconds (approx.70%) and a slowing of the supine egress & walk task from 14 to 21 seconds (approx.50%). Similar relationships were observed with strength/body weight and task performance. For the average person, a 20% reduction in strength/body weight (from 2.1 to 1.7 Nm/kg) resulted in a slowing of the ladder climb from 10.5 to 24 seconds (approx.128%) and a slowing of the supine egress & walk from 11 to 20 seconds (approx.82%). These data suggest that the single variable of either low body muscle strength or power, relative to body weight is predictive of about 50% of the variance in task performance time, and that considerable slowing in task performance is associated with relatively typical decrements in muscle performance seen with long duration spaceflight. The observation of a relatively linear relationship between strength/power and task time suggests that across the full spectrum of initial crew strengths and typical decrements in strength previously observed, that task performance would be expected to be slowed following long duration spaceflight. These data will be confirmed in actual spaceflight with subsequent studies.

Ploutz-Snyder, Lori↗

Intracranial Effects of Intermittent Lower Body Negative Pressure with Head Down Tilt Bed Rest: Comparison to Upright Posture

INTRODUCTION Spaceflight-associated neuro-ocular syndrome (SANS) affects a majority of astronauts during long-duration spaceflight. SANS is hypothesized to result from an unrelenting headward fluid shift that occurs in the microgravity environment. Altered intracranial structure and physiology documented in spaceflight and head-down tilt (HDT) experiments(1, 2) are also theorized to be related to chronic headward fluid shift and thereby can provide an independent quantitative assessment related to this mechanism. As a potential countermeasure, lower body negative pressure (LBNP) applied in the supine posture has shown efficacy in reducing headward fluid shift(3). However, it remains unknown if intermittent LBNP simulating daily upright posture fluid redistribution can mitigate SANS and intracranial changes associated with long-duration spaceflight. The goal of this study was to quantify the effects of daily application of LBNP or daily exposure to the upright posture on intracranial structure and physiology during long-term HDT in order to evaluate the potential efficacy of LBNP as a countermeasure to SANS. METHODS 22 healthy volunteers (11 men; 11 women; mean age = 35 years (SD=9.2)(age range = 24 to 52 years); mean BMI = 24.0 kg/m2 (SD=2.8)) completed an MRI study performed at the German Aerospace Facility in Cologne, Germany. Strict six-degree head-down tilt (HDT) bedrest was used as a spaceflight analog to induce a continuous headward fluid shift for 30 days. The subjects were divided equally into two groups of interventions: 1) LBNP for 3-hour sessions twice daily and 2) seated position for 3-hour sessions twice daily. Interventions were divided into morning and afternoon sessions for both groups. The LBNP intervention was maintained at 25 mmHg  2 mmHg. Pulse-gated MRI phase-contrast flow imaging was used to quantify cerebral artery stroke volume (CASV) and peak-to-peak cerebral spinal fluid (CSF) velocity (CSFVp-p) within the cerebral aqueduct. A 3D T1-MPRAGE sequence was used to quantify volumetric changes of the brain and intracranial CSF spaces using MRI Cloud software. MRI acquisitions were obtained at baseline (BDC, supine posture), 15 days into HDT (HDT15), 29 days into HDT (HDT29), and 12 days after recovery (R12, supine posture). The data were analyzed by a mixed model, which included intervention, time (four nominal levels BDC, HDT15, HDT29, R12), and intervention-time interaction as the fixed effects and included subject as a random effect. RESULTS Compared to BDC there was no statistically significant difference in CASV and CSFVp-p during HDT except for CASV at HDT29 (seated group) where there was a 1.7 mL (12%) decrease (P<0.01). Compared to BDC there was a statistically significant increase in intracranial volume (ICV; ICV = white matter + gray matter + CSF) for both interventions at HDT15 (Δ13 mL, 0.9 % (LBNP group); Δ15 mL, 1.0%, (seated group)) and HDT29 (Δ19 mL, 1.2%, (LBNP group); Δ23 mL, 1.5%) (seated group)) (All Ps<.001). Compared to baseline, lateral ventricular volume increased at HDT15 (Δ0.9 mL, 5.5%) and HDT29 (Δ1.8 mL, 10%)) for LBNP only (P=.001 for each). During HDT, white matter volume remained stable compared to baseline for both interventions. There were no significant intervention effects in the overall response to HDT (All Ps >.2). CONCLUSION LBNP had a similar response to the seated posture during 29 days of HDT. Although there was an increase in ICV and lateral ventricular volume with HDT there was no change in intracranial physiological parameters with LBNP suggesting an overall diminished response to the long-term effects of HDT. The lack of any significant increase in white matter volume during HDT with LBNP suggests maintenance of cerebral interstitial fluid transport. Final conclusions are pending the data collection for the control group (no intervention) which will be completed in 2023.

Larry A Kramer↗

Using Tri-Axial Accelerometers to Assess the Dynamic Control of Head Posture During Gait

Long duration spaceflight is known to cause a variety of biomedical stressors to the astronaut. One of the more functionally destabilizing effects of spaceflight involves microgravity-induced changes in vestibular or balance control. Balance control requires the integration of the vestibular, visual, and proprioceptive systems. In the microgravity environment, the normal gravity vector present on Earth no longer serves as a reference for the balance control system. Therefore, adaptive changes occur to the vestibular system to affect control of body orientation with altered, or non-present, gravity and/or proprioceptive inputs. Upon return to a gravity environment, the vestibular system must re-incorporate the gravity vector and gravity-induced proprioceptive inputs into the balance control regime. The result is often a period of postural instability, which may also be associated with space motion sickness (oscillopsia, nausea, and vertigo). Previous studies by the JSC Neuroscience group have found that returning astronauts often employ alterations in gait mechanics to maintain postural control during gait. It is believed that these gait alterations are meant to decrease the transfer of heel strike shock energy to the head, thus limiting the contradictory head and eye movements that lead to gait instability and motion sickness symptoms. We analyzed pre- and post-spaceflight tri-axial accelerometer data from the NASA/MIR long duration spaceflight missions to assess the heel to head transfer of heel strike shock energy during locomotion. Up to seven gait sessions (three preflight, four postflight) of head and shank (lower leg) accelerometer data was previously collected from six astronauts who engaged in space flights of four to six months duration. In our analysis, the heel to head transmission of shock energy was compared using peak vertical acceleration (a), peak jerk (j) ratio, and relative kinetic energy (a). A host of generalized movement variables was produced in an effort to isolate those that best highlighted vestibular adaptation due to spaceflight. Data suggest that astronauts used either head or body centered control to reduce the effects of heel strike shock on head position during normal walking at self-selected speeds. Moreover, the form of that control appears to fall under one of two categories: homeostatic or adaptive. Homeostatic control refers to tight constraint (small error) over the value of a given variable before and after spaceflight with little or no adaptive changes. Adaptive control refers to lesser constraint over a given movement variable with clear adaptation to earth gravity upon return from spaceflight. Heel strike shock absorption (ratio of heel to head peak acceleration) best-discriminated head and body centered control strategies. Further, peak jerk data was useful for illustrating pre- and postflight differences in segmental (shank versus head) movement energy. Results from kinetic energy analysis show high consistency between subjects and across test dates. Whether this result highlights a control strategy or is an artifact of approximating body segments using anthropometric tables is, at this point, unclear.

Lawrence, John H., III↗

TBS (Trabecular Bone Score) Expands Understanding of Spaceflight Effects on the Lumbar Spine of Long Duration Astronauts

Background: Bone loss due to long-duration spaceflight has been characterized by both DXA and QCT serial scans. It is unclear if these spaceflight-induced changes in bone mineral density and structure result in increased fracture incidence. NASA astronauts currently fly on 5-6-month missions on the International Space Station (ISS) and at least one 12-month mission is planned. While NASA has measured areal BMD (by DXA) and volumetric BMD (by QCT), and has estimated hip strength (by finite element models of QCT data, no method has yet been used to examine bone microarchitecture from lumbar spine (LS). DXA scans are routinely performed pre- and post-flight on all ISS astronauts to follow BMD changes associated with space flight. Trabecular Bone Score (TBS) is a relatively new method that measures grey-scale-level texture information extracted from lumbar spine DXA images and correlates with 3D parameters of bone micro-architecture. We evaluated the ability of LS TBS to discriminate changes in astronauts who have flown on ISS missions and to determine if TBS can provide additional information compared to DXA. Methods: LS (L1-4) DXA scans from 51 astronauts (mean age, 47 +/- 4) were divided into 3 groups based on the exercise regimes performed while onboard the ISS. Pre-ARED (exercise using a load-limited resistive exercise device, <300lb), ARED (exercise with a high-load resistive exercise device, up to 600lb) and a Bisphos group (ARED exercise and a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch). DXA scans were performed and analyzed on a Hologic Discovery W using the same technician for the pre- and postflight scans. LSC for the LS in our laboratory is 0.025 g/cm2. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. TBS precision was calculated from 16 comparable test subjects (0.0XX g/cm2). Data were preliminary analyzed using a paired, 2-tailed t-test for the difference between pre- and postflight means.

Sibonga, Jean D.↗

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.↗

Update of the Bisphosphonate ISS Flight Experiment

The bisphosphonate study is an international collaboration between the NASA and JAXA space agencies to investigate the potential value of antiresorptive drugs to mitigate the well-established bone changes associated with long-duration spaceflight. Our hypothesis is that an antiresorptive drug in combination with in-flight exercise will ameliorate bone loss and hypercalcuria during long-duration spaceflight. We have completed data analysis for 7 crewmembers treated with alendronate during flight and 3 of 10 controls without treatment. We previously reported the pre/postflight changes in bone density and the pre versus in-flight changes in various biomarkers in crewmembers taking alendronate during flight. The purpose of this report is to compare these results with the 12- month follow-up data. The table below presents these data as a percentage change from baseline either immediately postflight or in-flight (biochemical markers) with a 1-year follow-up.

LeBlanc, Adrian↗

Computational Modeling of Space Physiology

The Digital Astronaut Project (DAP), within NASAs Human Research Program, develops and implements computational modeling for use in the mitigation of human health and performance risks associated with long duration spaceflight. Over the past decade, DAP developed models to provide insights into space flight related changes to the central nervous system, cardiovascular system and the musculoskeletal system. Examples of the models and their applications include biomechanical models applied to advanced exercise device development, bone fracture risk quantification for mission planning, accident investigation, bone health standards development, and occupant protection. The International Space Station (ISS), in its role as a testing ground for long duration spaceflight, has been an important platform for obtaining human spaceflight data. DAP has used preflight, in-flight and post-flight data from short and long duration astronauts for computational model development and validation. Examples include preflight and post-flight bone mineral density data, muscle cross-sectional area, and muscle strength measurements. Results from computational modeling supplement space physiology research by informing experimental design. Using these computational models, DAP personnel can easily identify both important factors associated with a phenomenon and areas where data are lacking. This presentation will provide examples of DAP computational models, the data used in model development and validation, and applications of the model.

simulation↗

Behavioral Health and Performance Operations at the NASA Johnson Space Center: A Comprehensive Program that Addresses Flight and Spaceflight Duty Adaptability

NASA astronauts on active status require medical certification for aircraft flying duties as well as readiness for long duration spaceflight training, launch to the International Space Station (ISS), and mission continuation during spaceflight operations. Behavioral fitness and adaptability is an inherent component of medical certification at NASA and requires a unique approach that spans the professional life-span of all active astronauts. TOPIC: This presentation will address the Behavioral Health and Performance (BHP) operations program at the Johnson Space Center. Components of BHP operations include astronaut selection, as well as annual, elective, preflight, inflight, and postflight BHP assessments. Each aspect of the BHP operations program will be discussed, with a focus on behavioral fitness determination and resultant outcomes. Specifically, astronaut selection generates a rating of suitability for long duration spaceflight as well as psychiatric qualification; annual, preflight and postflight BHP assessments provoke a decision regarding the presence of any aeromedical concerns; and inflight assessment requires a conclusion pertaining to mission impact. The combination of these elements provide for a unique, comprehensive approach to flight and spaceflight adaptability. APPLICATIONS: Attendees will understand the differing facets of NASA's comprehensive BHP operations program that occurs over the course of an astronaut's career and be able to compare and contrast this to the Adaptability Rating for Military Aviation (ARMA) and proposed models presented by others on this panel.

Beven, G. E.↗

Change in Mouse Bone Turnover in Response to Microgravity on RR-1

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1ap21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23 decrease in bone fraction (p0.005) and 11.91 decrease in bone thickness (p0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n10) and vivarium controls (n10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37-days of spaceflight. To do this, we will analyze differences in bone morphometric parameters using MicroCT. The pelvis, femur, and tibia are key in supporting and distributing weight under normal conditions. Therefore, we expect to see altered remodeling in flight animals in response to microgravity with respect to ground controls. In combination with histomorphometry, these results will help elucidate the complex mechanisms underlying bone tissue maintenance and stem cell regeneration.

bone↗

Changes in Mouse Bone Turnover in Response to Microgravity

Mechanical unloading during spaceflight is known to adversely affect mammalian physiology. Our previous studies using the Animal Enclosure Module on short duration Shuttle missions enabled us to identify a deficit in stem cell based-tissue regeneration as being a significant concern for long-duration spaceflight. Specifically, we found that mechanical unloading in microgravity resulted in inhibition of differentiation of mesenchymal and hematopoietic stem cells in the bone marrow compartment. Also, we observed overexpression of a cell cycle arrest molecule, CDKN1a/p21, in osteoprecursor cells on the bone surface, chondroprogenitors in the articular cartilage, and in myofibers attached to bone tissue. Specifically in bone tissue during both short (15-day) and long (30-day) microgravity experiments, we observed significant loss of bone tissue and structure in both the pelvis and the femur. After 15-days of microgravity on STS-131, pelvic ischium displayed a 6.23% decrease in bone fraction (p=0.005) and 11.91% decrease in bone thickness (p=0.002). Furthermore, during long-duration spaceflight we observed onset of an accelerated aging-like phenotype and osteoarthritic disease state indicating that stem cells within the bone tissue fail to repair and regenerate tissues in a normal manner, leading to drastic tissue alterations in response to microgravity. The Rodent Research Hardware System provides the capability to investigate these effects during long-duration experiments on the International Space Station. During the Rodent Research-1 mission 10 16-week-old female C57Bl/6J mice were exposed to 37-days of microgravity. All flight animals were euthanized and frozen on orbit for future dissection. Ground (n=10) and vivarium controls (n=10) were housed and processed to match the flight animal timeline. During this study we collected pelvis, femur, and tibia from all animal groups to test the hypothesis that stem cell-based tissue regeneration is significantly altered after 37-days of spaceflight. To do this, we will analyze differences in bone morphometric parameters using MicroCT. The pelvis, femur, and tibia are key in supporting and distributing weight under normal conditions. Therefore, we expect to see altered remodeling in flight animals in response to microgravity with respect to ground controls. In combination with histomorphometry, these results will help elucidate the complex mechanisms underlying bone tissue maintenance and stem cell regeneration.

microgravity↗

Reduction in Dynamic Visual Acuity Reveals Gaze Control Changes Following Spaceflight

INTRODUCTION: Exposure to microgravity causes adaptive changes in eye-head coordination that can lead to altered gaze control. This could affect postflight visual acuity during head and body motion. The goal of this study was to characterize changes in dynamic visual acuity after long-duration spaceflight. METHODS: Dynamic Visual Acuity (DVA) data from 14 astro/cosmonauts were collected after long-duration (~6 months) spaceflight. The difference in acuity between seated and walking conditions provided a metric of change in the subjects ability to maintain gaze fixation during self-motion. In each condition, a psychophysical threshold detection algorithm was used to display Landolt ring optotypes at a size that was near each subject s acuity threshold. Verbal responses regarding the orientation of the gap were recorded as the optotypes appeared sequentially on a computer display 4 meters away. During the walking trials, subjects walked at 6.4 km/h on a motorized treadmill. RESULTS: A decrement in mean postflight DVA was found, with mean values returning to baseline within 1 week. The population mean showed a consistent improvement in DVA performance, but it was accompanied by high variability. A closer examination of the individual subject s recovery curves revealed that many did not follow a pattern of continuous improvement with each passing day. When adjusted on the basis of previous long-duration flight experience, the population mean shows a "bounce" in the re-adaptation curve. CONCLUSION: Gaze control during self-motion is altered following long-duration spaceflight and changes in postflight DVA performance indicate that vestibular re-adaptation may be more complex than a gradual return to normal.

Peters, Brian T.↗