Spaceflight Analog Research Articles

Using noninvasive imaging to assess manual lymphatic drainage on lymphatic/venous responses in a spaceflight analog

This retrospective case series (clinicaltrials.gov NCT06405282) used noninvasive imaging devices (NIID) to assess the effect of manual lymphatic drainage (MLD) on dermal/venous fluid distribution, perfusion, and temperature alterations of the head, neck, upper torso, and legs while in the 6-degree head-down tilt validated spaceflight analog. A lymphatic fluid scanner measured tissue dielectric constant levels. Near-infrared spectroscopy assessed perfusion, by measuring tissue oxygenation saturation. Long-wave infrared thermography measured tissue temperature gradients. Fifteen healthy, university students participated. NIID assessments were taken 1 minute after assuming the HDT position and then every 30 minutes, with MLD administered from 180 to 195 minutes. Subjects returned to the sitting position and were assessed at post-225 min NIID demonstrated significant changes from baseline (p < 0.01), although these changes at areas of interest varied. MLD had a reverse effect on all variables. NIID assessment supported the potential use of MLD to mitigate fluid shifts during a spaceflight analog.

Microbiology of human spaceflight: microbial responses to mechanical forces that impact health and habitat sustainability.

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches. Here, we review biological and physical mechanisms that regulate microbial responses to spaceflight and spaceflight analog environments from both the microbe and host-microbe perspective that are relevant to human health and habitat sustainability. We highlight instrumentation and technology used in spaceflight microbiology experiments, their limitations, and advances necessary to enable next-generation research. As spaceflight experiments are relatively rare, we discuss ground-based analogs that mimic aspects of microbial responses to reduced gravity in spaceflight, including those that reduce mechanical forces of fluid flow over cell surfaces which also simulate conditions encountered by microorganisms during their terrestrial lifecycles. As spaceflight mission durations increase with traditional astronauts and commercial space programs send civilian crews with underlying health conditions, microorganisms will continue to play increasingly critical roles in health and habitat sustainability, thus defining a new dimension of occupational health. The ability of microorganisms to adapt, survive, and evolve in the spaceflight environment is important for future human space endeavors and provides opportunities for innovative biological and technological advances to benefit life on Earth.

Effect of artificial gravity on neurocognitive performance during head-down tilt bedrest

This study evaluated the acute and chronic effects of intermittent and continuous Artificial Gravity (AG) on cognitive performance during 60 days of Head-down tilt bedrest (HDTBR), a well-established ground-based spaceflight analogue method. Participants were randomly assigned to three groups: intermittent AG, continuous AG, and HDTBR control group without AG exposure. Task performance and electrophysiological measures of attention and working memory were investigated during Simple and Complex tasks in the Visual and the Auditory modality. Compared to baseline, faster reaction time and better accuracy was present during HDTBR regarding the Complex tasks, however, the practice effect was diminished in the three HDTBR groups compared to an ambulatory control group. Brain potentials showed a modality-specific decrease, as P3a was decreased only in the Auditory, while P3b decreased in the Visual modality. No evidence for acute or chronic AG-related cognitive impairments during HDTBR was found.

Daily use of veno-constrictive thigh cuffs during 30 days of strict 6° head-down tilt bedrest to reverse the headward fluid shift

Introduction: Chronic exposure to weightlessness induces a persistent headward fluid shift, which may contribute to the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). Strict 6° head-down tilt bedrest (HDTBR) is a spaceflight analog that induces a headward fluid shift and development of SANS findings, enabling the evaluation of potential countermeasures. Lower body exercise can induce a sustained post-exercise hyperemia thereby shifting blood away from the central circulation. In addition, veno-constrictive thigh cuffs (VTC) can sequester blood volume in the legs. The purpose of this study was to determine whether 6 hours of daily VTC use following cycling exercise (Ex+VTC) could reverse the headward fluid shift during 30 days of strict 6° HDTBR. We hypothesized that Ex+VTC would sequester fluid in the legs leading to increased thigh circumference and reduced stroke volume (SV), cardiac output (CO), internal jugular vein (IJV) cross-sectional area (CSA) and pressure, and intraocular pressure (IOP). Methods: Participants were randomly assigned to a Control (n=12, 6 female) or Ex+VTC (n=12, 4 female) group and completed baseline data collection (BDC) in the seated and supine posture followed by 30 days of strict 6° HDTBR. The Ex+VTC group completed a maximal exercise test on a cycle ergometer in 6° HDT posture during BDC to establish work rates during HDTBR. The Ex+VTC group performed 10 minutes of light cycle exercise, cycled for 45 minutes at 45% of their max wattage, and then donned VTC to ~50 mmHg for 6 hours on 6 of 7 days per week during HDTBR. Data were collected before exercise and 30 minutes and 6 hours after exercise and donning VTCs on days 3, 17, and 29 of HDTBR. Controls were studied at similar time points. Days were nested within the models. Mixed models were used to determine differences between groups in the change in thigh circumference measured using a flexible tape measure, bilateral IOP measured using tonometry, CO measured using the inert gas rebreathe technique (Innocor), and ultrasound of bilateral IJV CSA and pressure from before to 30 min and 6 hours after use of the countermeasure. Left and right IJV and IOP data were nested within each participant. Results: The Ex+VTC group completed all exercise sessions followed by 6 hours of VTC use. Compared to Control, thigh circumference was greater after 30 minutes (+1.3 vs. -0.2 cm, p&lt;0.001) and 6 hours of VTC use (+2.5 cm vs. -0.1 cm in controls, p&lt;0.001). SV (-38 vs. 2 ml, p&lt;0.001) and CO (-1.5 vs. 0.3 L/min, p&lt;0.001) were reduced at 30 minutes and 6 hours of VTC use (SV: -30 vs. 5 ml, p&lt;0.001; CO: -1.1 vs. 0.6 L/min, p&lt;0.001) compared to Control. IJV CSA and pressure were reduced at 30 minutes (CSA, p&lt;0.001; pressure, p=0.001) and 6 hours of VTC use (CSA, p&lt;0.001; pressure, p=0.007). IOP was not different compared to Control. Conclusions:Use of VTC for 6 hours after 45 minutes of exercise successfully sequestered fluid in the legs, leading to a reduction in central blood volume, IJV CSA, and IJV pressure. Thus, an Ex+VTC countermeasure resulted in a partial fluid shift reversal. This research was supported by the NASA Human Research Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

When people start getting real: The Group Living Skills Survey for extreme work environments.

Group living skills (GLS), that is, being tidy and considerate of others, are an important skillset for teams who live and work together. However, this construct does not have a validated measure to enable an understanding of how group living skills influence team dynamics over time. We developed and validated a short measure of group living skills for teams living in extreme work environments. We collected data from 83 individuals in 24 teams living and working in space and spaceflight analog environments on missions of 45-240 days. We provide evidence of reliability and validity for the GLS Survey over time and identify a two-factor structure. We also demonstrate its use as a measure of team-level dynamics and its utility as a sociometric measure to identify a person's degree of group living skills. We outline recommendations for using this new measure in future research and applied settings to understand this unique aspect of teams living and working together.

Effects of long-term closed and socially isolating spaceflight analog environment on default mode network connectivity as indicated by fMRI

Long-term manned spaceflight and extraterrestrial planet settlement become the focus of space powers. However, the potential influence of closed and socially isolating spaceflight on the brain function remains unclear. A 180-day controlled ecological life support system integrated experiment was conducted, establishing a spaceflight analog environment to explore the effect of long-term socially isolating living. Three crewmembers were enrolled and underwent resting-state fMRI scanning before and after the experiment. We performed both seed-based and network-based analyses to investigate the functional connectivity (FC) changes of the default mode network (DMN), considering its key role in multiple higher-order cognitive functions. Compared with normal controls, the leader of crewmembers exhibited significantly reduced within-DMN and between-DMN FC after the experiment, while two others exhibited opposite trends. Moreover, individual differences of FC changes were further supported by evidence from behavioral analyses. The findings may shed new light on the development of psychological protection for space exploration.

Dynamic changes in perivascular space morphology predict signs of spaceflight-associated neuro-ocular syndrome in bed rest

During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Collaborative System Usability in Spaceflight Analog Environments through Remote Observations

The conventional design cycle in human–computer interaction faces significant challenges when applied to users in isolated settings, such as astronauts in extreme environments. Challenges include obtaining user feedback and effectively tracking human–software/human–human dynamics during system interactions. This study addresses these issues by exploring the potential of remote conversation analysis to validate the usability of collaborative technology, supplemented with a traditional post hoc survey approach. Specifically, we evaluate an integrated timeline software tool used in NASA’s Human Exploration Research Analog. Our findings indicate that voice recordings, which focus on the topical content of intra-crew speech, can serve as non-intrusive metrics for essential dynamics in human–machine interactions. The results emphasize the collaborative nature of the self-scheduling process and suggest that tracking conversations may serve as a viable proxy for assessing workload in remote environments.

Development of optic disc edema during 30 days of hypercapnic head-down tilt bed rest is associated with short sleep duration and blunted temperature amplitude.

Sleep and circadian temperature disturbances occur with spaceflight and may, in part, result from the chronically elevated carbon dioxide (CO2) levels on the international space station. Impaired sleep may contribute to decreased glymphatic clearance and, when combined with the chronic headward fluid shift during actual spaceflight or the spaceflight analog head-down tilt bed rest (HDTBR), may contribute to the development of optic disc edema. We determined if strict HDTBR combined with mildly elevated CO2 levels influenced sleep and core temperature and was associated with the development of optic disc edema. Healthy participants (5 females) aged 25-50 yr, underwent 30 days of strict 6° HDTBR with ambient Pco2 = 4 mmHg. Measures of sleep, 24-h core temperature, overnight transcutaneous CO2, and Frisén grade edema were made pre-HDTBR, on HDTBR days 4, 17, 28, and post-HDTBR days 4 and 10. During all HDTBR time points, sleep, core temperature, and overnight transcutaneous CO2 were not different than the pre-HDTBR measurements. However, independent of the HDTBR intervention, the odds ratios {mean [95% confidence interval (CI)]} for developing Frisén grade optic disc edema were statistically significant for each hour below the mean total sleep time (2.2 [1.1-4.4]) and stage 2 nonrapid eye movement (NREM) sleep (4.8 [1.3-18.6]), and above the mean for wake after sleep onset (3.6 [1.2-10.6]) and for each 0.1°C decrease in core temperature amplitude below the mean (4.0 [1.4-11.7]). These data suggest that optic disc edema occurring during HDTBR was more likely to occur in those with short sleep duration and/or blunted temperature amplitude.NEW & NOTEWORTHY We determined that sleep and 24-h core body temperature were unaltered by 30 days exposure to the spaceflight analog strict 6° head-down tilt bed rest (HDTBR) in a 0.5% CO2 environment. However, shorter sleep duration, greater wake after sleep onset, and lower core temperature amplitude present throughout the study were associated with the development of optic disc edema, a key finding of spaceflight-associated neuro-ocular syndrome.

Vibrotactile feedback as a countermeasure for spatial disorientation.

Spaceflight can make astronauts susceptible to spatial disorientation which is one of the leading causes of fatal aircraft accidents. In our experiment, blindfolded participants used a joystick to balance themselves while inside a multi-axis rotation device (MARS) in either the vertical or horizontal roll plane. On Day 1, in the vertical roll plane (Earth analog condition) participants could use gravitational cues and therefore had a good sense of their orientation. On Day 2, in the horizontal roll plane (spaceflight analog condition) participants could not use gravitational cues and rapidly became disoriented and showed minimal learning and poor performance. One potential countermeasure for spatial disorientation is vibrotactile feedback that conveys body orientation provided by small vibrating devices applied to the skin. Orientation-dependent vibrotactile feedback provided to one group enhanced performance in the spaceflight condition but the participants reported a conflict between the accurate vibrotactile cues and their erroneous perception of their orientation. Specialized vibrotactile training on Day 1 provided to another group resulted in significantly better learning and performance in the spaceflight analog task with vibrotactile cueing. In this training, participants in the Earth analog condition on Day 1 were required to disengage from the task of aligning with the gravitational vertical encoded by natural vestibular/somatosensory afference and had to align with randomized non-vertical directions of balance signaled by vibrotactile feedback. At the end of Day 2, we deactivated the vibrotactile feedback after both vibration-cued groups had practiced with it in the spaceflight analog condition. They performed as well as the group who did not have any vibrotactile feedback. We conclude that after appropriate training, vibrotactile orientation feedback augments dynamic spatial orientation and does not lead to any negative dependence.

Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume.

Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3-4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60d HDTBR at the German Aerospace Center's:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3-4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.

Impact of daily artificial gravity on autonomic cardiovascular control following 60-day head-down tilt bed rest.

Impaired cardiovascular autonomic control following space flight or immobilization may limit the ability to cope with additional hemodynamic stimuli. Head-down tilt bedrest is an established terrestrial analog for space flight and offers the opportunity to test potential countermeasures for autonomic cardiovascular deconditioning. Previous studies revealed a possible benefit of daily artificial gravity on cardiovascular autonomic control following head-down tilt bedrest, but there is a need for efficiency in a long-term study before an artificial gravity facility would be brought to space. We hypothesized that artificial gravity through short-arm centrifugation attenuates functional adaptions of autonomic function during head-down tilt bed rest. 24 healthy persons (8 women, 33.4 ± 9.3 years, 24.3 ± 2.1 kg/m2) participated in the 60-day head-down tilt bed rest (AGBRESA) study. They were assigned to three groups, 30 min/day continuous, or 6(5 min intermittent short-arm centrifugation, or a control group. We assessed autonomic cardiovascular control in the supine position and in 5 minutes 80° head-up tilt position before and immediately after bed rest. We computed heart rate variability (HRV) in the time (rmssd) and frequency domain, blood pressure variability, and baroreflex sensitivity (BRS). RR interval corrected rmssd was reduced supine (p = 0.0358) and during HUT (p = 0.0161). Heart rate variability in the high-frequency band (hf-RRI; p = 0.0004) and BRS (p < 0.0001) decreased, whereas blood pressure variability in the low-frequency band (lf-SBP, p = 0.0008) increased following bedrest in all groups. We did not detect significant interactions between bedrest and interventions. We conclude that up to daily 30 min of artificial gravity on a short-arm centrifuge with 1Gz at the center of mass do not suffice to prevent changes in autonomic cardiovascular control following 60-day of 6° head-down tilt bed rest. Clinical Trial Registration: https://drks.de/search/en/trial/DRKS00015677, identifier, DRKS00015677.

Human gut microbiome and metabolite dynamics under simulated microgravity

ABSTRACT The Artificial Gravity Bed Rest – European Space Agency (AGBRESA) study was the first joint bed rest study by ESA, DLR, and NASA that examined the effect of simulated weightlessness on the human body and assessed the potential benefits of artificial gravity as a countermeasure in an analog of long-duration spaceflight. In this study, we investigated the impact of simulated microgravity on the gut microbiome of 12 participants during a 60-day head-down tilt bed rest at the :envihab facilities. Over 60 days of simulated microgravity resulted in a mild change in the gut microbiome, with distinct microbial patterns and pathway expression in the feces of the countermeasure group compared to the microgravity simulation-only group. Additionally, we found that the countermeasure protocols selectively increased the abundance of beneficial short-chain fatty acids in the gut, such as acetate, butyrate, and propionate. Some physiological signatures also included the modulation of taxa reported to be either beneficial or opportunistic, indicating a mild adaptation in the microbiome network balance. Our results suggest that monitoring the gut microbial catalog along with pathway clustering and metabolite profiling is an informative synergistic strategy to determine health disturbances and the outcome of countermeasure protocols for future space missions.

Palmer Station, Antarctica: A ground-based spaceflight analog suitable for validation of biomedical countermeasures for deep space missions

Astronauts are known to exhibit a variety of immunological alterations during spaceflight including changes in leukocyte distribution and plasma cytokine concentrations, a reduction in T-cell function, and subclinical reactivation of latent herpesviruses. These alterations are most likely due to mission-associated stressors including circadian misalignment, microgravity, isolation, altered nutrition, and increased exposure to cosmic radiation. Some of these stressors may also occur in terrestrial situations. This study sought to determine if crewmembers performing winterover deployment at Palmer Station, Antarctica, displayed similar immune alterations. The larger goal was to validate a ground analog suitable for the evaluation of countermeasures designed to protect astronauts during future deep space missions. For this pilot study, plasma, saliva, hair, and health surveys were collected from Palmer Station, Antarctica, winterover participants at baseline, and at five winterover timepoints. Twenty-six subjects consented to participate over the course of two seasons. Initial sample processing was performed at Palmer, and eventually stabilized samples were returned to the Johnson Space Center for analysis. A white blood cell differential was performed (real time) using a fingerstick blood sample to determine alterations in basic leukocyte subsets throughout the winterover. Plasma and saliva samples were analyzed for 30 and 13 cytokines, respectively. Saliva was analyzed for cortisol concentration and three latent herpesviruses (DNA by qPCR), EBV, HSV1, and VZV. Voluntary surveys related to general health and adverse clinical events were distributed to participants. It is noteworthy that due to logistical constraints caused by COVID-19, the baseline samples for each season were collected in Punta Arenas, Chile, after long international travel and during isolation. Therefore, the Palmer pre-mission samples may not reflect a true normal ‘baseline’. Minimal alterations were observed in leukocyte distribution during winterover. The mean percentage of monocyte concentration elevated at one timepoint. Plasma G-CSF, IL1RA, MCP-1, MIP-1β, TNFα, and VEGF were decreased during at least one winterover timepoint, whereas RANTES was significantly increased. No statistically significant changes were observed in mean saliva cytokine concentrations. Salivary cortisol was substantially elevated throughout the entire winterover compared to baseline. Compared to shedding levels observed in healthy controls (23%), the percentage of participants who shed EBV was higher throughout all winterover timepoints (52–60%). Five subjects shed HSV1 during at least one timepoint throughout the season compared to no subjects shedding during pre-deployment. Finally, VZV reactivation, common in astronauts but exceptionally rare in ground-based stress analogs, was observed in one subject during pre-deployment and a different subject at WO2 and WO3. These pilot data, somewhat influenced by the COVID-19 pandemic, do suggest that participants at Palmer Station undergo immunological alterations similar to, but likely in reduced magnitude, as those observed in astronauts. We suggest that winterover at Palmer Station may be a suitable test analog for spaceflight biomedical countermeasures designed to mitigate clinical risks for deep space missions.

Longitudinal Changes in Cerebral Perfusion, Perivascular Space Volume, and Ventricular Volume in a Healthy Cohort Undergoing a Spaceflight Analog.

A global decrease in brain perfusion has recently been reported during exposure to a ground-based spaceflight analog. Considering that CSF and glymphatic flow are hypothesized to be propelled by arterial pulsations, it is unknown whether a change in perfusion would impact these CSF compartments. The aim of the current study was to evaluate the relationship among changes in cerebral perfusion, ventricular volume, and perivascular space volume before, during, and after a spaceflight analog. Eleven healthy participants underwent 30 days of bed rest at 6° head-down tilt with 0.5% atmospheric CO2 as a spaceflight analog. For each participant, 6 MR imaging brain scans, including perfusion and anatomic-weighted T1 sequences, were obtained before, during, and after the analog period. Global perfusion, ventricular volume, and perivascular space volume time courses were constructed and evaluated with repeated measures ANOVAs. Global perfusion followed a divergent time trajectory from ventricular and perivascular space volume, with perfusion decreasing during the analog, whereas ventricular and perivascular space volume increased (P < .001). These patterns subsequently reversed during the 2-week recovery period. The patterns of change in brain physiology observed in healthy participants suggest a relationship between cerebral perfusion and CSF homeostasis. Further study is warranted to determine whether a causal relationship exists and whether similar neurophysiologic responses occur during spaceflight.

Layperson Physiological Tolerance and Operational Performance in Centrifuge-Simulated Spaceflight.

INTRODUCTION: Prior study has indicated that individuals of varied age, medical history, and limited-to-no experience tolerate spaceflight conditions. We sought to expand upon the understanding of layperson response to hypergravity conditions expected in commercial spaceflight by exposing subjects, following minimal training, to centrifuge-simulated, high-fidelity commercial spaceflight profiles. We further explored how these individuals perform in simulated operational activities during and following hypergravity.METHODS: Volunteer subjects participated in up to five centrifuge runs (maximum +4.0 Gz, +4.5 Gx, 6.1 G resultant; onset rate <0.5 Gz · s-1, ≤1 Gx · s-1). Profiles included two winged spacecraft simulations with sequential and combined +Gx/+Gz and two capsule simulations representing nominal +Gx launch and reentry. The final profile simulated a capsule launch abort, with a more dynamic cycling of +Gx exposures and oscillatory multi-axis exposures simulating parachutes and water motion. Touchscreen tablets were used to administer pattern-replication tasks during and after profiles.RESULTS: A total of 46 subjects participated, including 4 diabetics and 9 with cardiac disease. There was increased frequency of motion sickness, subjectively associated with capsule-type profiles, and increased termination of participation compared to prior studies. There was no association between medical history, age, sex, or motion sickness history and tolerance or noncompletion. Tablet test errors were common; accuracy and time to completion were associated with age. There was no association between any time metric or accuracy and sex.DISCUSSION: This study improves understanding of layperson tolerance in commercial spaceflight analog conditions, and the capsular profiles broaden the applicability of the findings. The frequency of task errors highlights the potential for mistakes in operational activities when performed by laypersons.Blue RS, Ong KM, Ray K, Menon A, Mateus J, Auñón-Chancellor S, Shah R, Powers W. Layperson physiological tolerance and operational performance in centrifuge-simulated spaceflight. Aerosp Med Hum Perform. 2023; 94(8):584-595.

Artificial gravity during a spaceflight analog alters brain sensory connectivity

Spaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated whether AG alters resting-state brain functional connectivity changes during head-down tilt bed rest (HDBR), a spaceflight analog. Participants underwent 60 days of HDBR. Two groups received daily AG administered either continuously (cAG) or intermittently (iAG). A control group received no AG. We assessed resting-state functional connectivity before, during, and after HDBR. We also measured balance and mobility changes from pre- to post-HDBR. We examined how functional connectivity changes throughout HDBR and whether AG is associated with differential effects. We found differential connectivity changes by group between posterior parietal cortex and multiple somatosensory regions. The control group exhibited increased functional connectivity between these regions throughout HDBR whereas the cAG group showed decreased functional connectivity. This finding suggests that AG alters somatosensory reweighting during HDBR. We also observed brain-behavioral correlations that differed significantly by group. Control group participants who showed increased connectivity between the putamen and somatosensory cortex exhibited greater mobility declines post-HDBR. For the cAG group, increased connectivity between these regions was associated with little to no mobility declines post-HDBR. This suggests that when somatosensory stimulation is provided via AG, functional connectivity increases between the putamen and somatosensory cortex are compensatory in nature, resulting in reduced mobility declines. Given these findings, AG may be an effective countermeasure for the reduced somatosensory stimulation that occurs in both microgravity and HDBR.

Increased hemodynamic pulsatility in the cerebral microcirculation during parabolic flight-induced microgravity: A computational investigation

Ground-based spaceflight analogs play a crucial role to understand and predict cardiovascular alterations during microgravity in a controlled and affordable way. Despite their extensive use in recent years, cerebral hemodynamics in microgravity remains poorly understood, multifaceted, and definitive data are still missing, due to the limited number and different duration of experiments, the individual variability, and the intrinsic difficulty in obtaining direct clinical measures. However, there is growing evidence that hemodynamic changes are among the underlying causes of neurological dysfunctions, such as the Spaceflight Associated Neuro-ocular Syndrome (SANS). We proposed to investigate the cerebral hemodynamics during supine posture parabolic flight by means of a validated computational approach, combining a 0D-1D central-systemic cardiovascular model together with a 0D cerebrovascular model. Present findings showed that, although with over- and under-shoots in the transition from one gravitational environment to the other, beat-averaged pressure and flow rate steady state values did not greatly vary between 0g and 1g due to the cerebral autoregulation. On the contrary, in microgravity there was an augmented hemodynamic pulsatility which increased towards the deep cerebral microcirculation. The greater pulsatility, inducing a higher variability of maximum and minimum values reached within each beat, was here observed for the first time also for important cerebral markers, such as the intracranial pressure, the cerebrospinal fluid circulation, and the cerebral blood flow. The proposed approach offers novel insights on how hemodynamic alterations, such as cerebral hypoperfusions and intracranial pressure fluctuations, can contribute to explain neurovestibular dysfunctions emerging during short-term exposure to 0g, including the onset of nausea, SANS and cognitive fatigue.

Bone metabolism during strict head-down tilt bed rest and exposure to elevated levels of ambient CO2

Astronauts on the International Space Station are exposed to levels of atmospheric carbon dioxide (CO2) above typical terrestrial levels. We explored the possibility that increased levels of ambient CO2 further stimulate bone resorption during bed rest. We report here data from 2 ground-based spaceflight analog studies in which 12 male and 7 female subjects were placed in a strict 6° head-down tilt (HDT) position for either 30 days at 0.5% ambient CO2 or 60 days with nominal environmental exposure to CO2. Bone mineral density (BMD) and bone mineral content (BMC) were determined using dual-energy X-ray absorptiometry (DXA). Blood and urine were collected before and after HDT for biochemical analysis. No change was detected in either BMD or BMC, as expected given the study duration. Bone resorption markers increased after bed rest as expected; however, elevated CO2 had no additive effect. Elevated CO2 did not affect concentrations of minerals in serum and urine. Serum parathyroid hormone and 1,25-dihydroxyvitamin D were both reduced after bed rest, likely secondary to calcium efflux from bone. In summary, exposure to 0.5% CO2 for 30 days did not exacerbate the typical bone resorption response observed after HDT bed rest. Furthermore, results from these strict HDT studies were similar to data from previous bed rest studies, confirming that strict 30–60 days of HDT can be used to evaluate changes in bone metabolism. This is valuable in the continuing effort to develop and refine efficacious countermeasure protocols to mitigate bone loss during spaceflight in low-Earth orbit and beyond.

Plasma proteome profiling of healthy subjects undergoing bed rest reveals unloading-dependent changes linked to muscle atrophy.

Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed-ridden patients care, but it is also a ground-based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. We applied mass spectrometry-based proteomics to measure plasma protein abundance changes in response to 10days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age-matched controls. Our analysis resulted in the quantification of over 500 proteins. Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin-4 increased 1.6-fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P=0.02) and decreased to 0.6-fold the initial abundance after 2days of recovery at normal daily activity (R+2, 2.7E9, P=3.3E-4); the extracellular matrix protein lumican was decreased to 0.7-fold (1.2E9 vs. 8.5E8, P=1.5E-4) at BR10 and remained as low at R+2. We identified six proteins distinguishing subjects developing unloading-mediated muscle atrophy (decrease of >4% of quadriceps cross-sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone-binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P=0.001). Haptoglobin-related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy-prone and atrophy-resistant subjects after 10days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity-triggered muscle loss in humans.