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.

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.

Changes in real-world walking speed following 60-day bed-rest.

The aim of this work was to explore whether real-world walking speed (RWS) would change as a consequence of 60-day bed-rest. The main hypothesis was that daily RWS would decrease after the bed-rest, with a subsequent recovery during the first days of re-ambulation. Moreover, an exploratory analysis was done in order to understand whether there is an agreement between the loss in RWS after bed-rest and the loss in the maximum oxygen uptake capacity (VO2max), or the loss in maximal vertical jump power (JUMP) respectively. Twenty-four subjects were randomly assigned to one of three groups: a continuous artificial gravity group, an intermittent artificial gravity group, or a control group. The fitted linear mixed effects model showed a significant decrease (p < 0.001) of RWS after the 60-day bed-rest and a subsequent increase (p < 0.001) of RWS during the 14-day recovery period in the study facility. No or little agreement was found between the loss in RWS and the loss in VO2max capacity or the loss in maximal vertical jumping power (RWS vs. VO2max: p = 0.81, RWS vs. JUMP: p = 0.173). Decreased RWS after bed-rest, with a follow-up recovery was observed for all three groups, regardless of the training intervention. This suggests that RWS, also in these settings, was able to reflect a de-conditioning and follow-up recovery process.

The impact of bed rest on human skeletal muscle metabolism.

Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.

Human gut microbiome and metabolite dynamics under simulated microgravity.

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.

The future of spaceflight will involve missions beyond the International Space Station or the Moon and astronaut's health will be challenged by a harsh space environment for longer periods. In the last decade, the intestine has gained importance in dictating overall physiology and we explore it as an additional indicator of health during our ground-based bed rest study simulating microgravity for 60 days. Through the analysis of fecal proteins, we compile the catalog of microbes colonizing the gut of the 12 participants along with the implicated biological activity of the proteins and another 9 lipid analytes. We found specific microbes associated with recovery or healthy status in our subjects to be increased during spaceflight countermeasure conditions and inverse observations in subjects subjected to perilous spaceflight simulation. Our approach improves the functional characterization of the gut by the use of noninvasive methodology correlating the microbial composition of human stool samples with physiological status.

Daily Artificial Gravity Partially Mitigates Vestibular Processing Changes Associated with Head-down Tilt Bedrest.

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting and adaptation. The unloading effects can be modelled using head down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the physiological declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 minutes of daily AG to counteract brain and behavior changes that arise from 60 days of HDT. One group of participants received 30 minutes of AG daily (AG; n = 16) while in HDT, and another group served as controls, spending 60 days in HDT bedrest with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans from participants as they received vestibular stimulation. We collected these data prior to, during (2x), and post HDT. We assessed brain activation initially in 10 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in brain activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased cerebellar activation specific to the HDT phase. Additionally, those that received AG and showed little pre- to post-bed rest changes in left OP2 activation during HDT had better post-HDT balance performance. Exploratory whole brain analyses identified increased pre- to during-HDT activation in the CTRL group in the right precentral gyrus and the right inferior frontal gyrus specific to HDT, where the AG group maintained pre-HDT activation levels. Together, these results indicate that AG could mitigate brain activation changes in vestibular processing in a manner that is associated with better balance performance after HDT.

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.

Daily artificial gravity is associated with greater neural efficiency during sensorimotor adaptation.

Altered vestibular signaling and body unloading in microgravity results in sensory reweighting and adaptation. Microgravity effects are well-replicated in head-down tilt bed rest (HDBR). Artificial gravity (AG) is a potential countermeasure to mitigate the effects of microgravity on human physiology and performance. We examined the effectiveness of daily AG for mitigating brain and/or behavioral changes in 60 days of HDBR. One group received AG for 30 minutes daily (AG; n = 16) and a control group spent the same time in HDBR but received no AG (CTRL; n = 8). All participants performed a sensorimotor adaptation task five times during fMRI scanning: twice prior to HDBR, twice during HDBR, and once following HDBR. The AG group showed similar behavioral adaptation effects compared with the CTRLs. We identified decreased brain activation in the AG group from pre to late HDBR in the cerebellum for the task baseline portion and in the thalamus, calcarine, cuneus, premotor cortices, and superior frontal gyrus in the AG group during the early adaptation phase. The two groups also exhibited differential brain-behavior correlations. Together, these results suggest that AG may result in a reduced recruitment of brain activity for basic motor processes and sensorimotor adaptation. These effects may stem from the somatosensory and vestibular stimulation that occur with AG.

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.

Assessing the effects of artificial gravity in an analog of long-duration spaceflight: The protocol and implementation of the AGBRESA bed rest study.

A comprehensive strategy is required to mitigate risks to astronauts' health, well-being, and performance. This strategy includes developing countermeasures to prevent or reduce adverse responses to the stressors astronauts encounter during spaceflight, such as weightlessness. Because artificial gravity (AG) by centrifugation simultaneously affects all physiological systems, AG could mitigate the effects of weightlessness in multiple systems. In 2019, NASA and the German Aerospace Center conducted a 60-days Artificial Gravity Bed Rest Study with the European Space Agency (AGBRESA). The objectives of this study were to 1) determine if 30 min of AG daily is protective during head down bed rest, and 2) compare the protective effects of a single daily bout (30 min) of AG versus multiple daily bouts (6 × 5 min) of AG (1 Gz at the center of mass) on physiological functions that are affected by weightlessness and by head-down tilt bed rest. The AGBRESA study involved a comprehensive suite of standard and innovative technologies to characterize changes in a broad spectrum of physiological systems. The current article is intended to provide a detailed overview of the methods used during AGBRESA.

Iron metabolism regulation in females and males exposed to simulated microgravity: results from the randomized trial Artificial Gravity Bed Rest-European Space Agency (AGBRESA).

BACKGROUND: Iron metabolism imbalance could contribute to physical deconditioning experienced by astronauts due to its essential role in energy metabolism, cellular respiration, and oxygen transport. OBJECTIVES: In this clinical exploratory study, we wanted to determine whether artificial gravity (AG) training modulated iron metabolism, RBC indices, and body lean mass in healthy male and female participants exposed to head-down tilt (HDT) bed rest, the reference ground-based model of microgravity. METHODS: We recruited 8 healthy female and 16 healthy male participants who were all exposed to HDT bed rest for 60 d. In addition, they were assigned to 3 experimental groups (n = 8/each): controls, continuous AG training in a short-arm centrifuge (1 × 30 min/d), and intermittent AG training (6 × 5 min/d). RESULTS: The iron metabolism responses to simulated microgravity of the AG training groups did not differ significantly from the responses of controls. Independently from AG, we found that both serum iron concentrations (+31.3%, P = 0.027) and transferrin saturation levels (+28.4%, P = 0.009) increased in males after 6 d of HDT bed rest, as well as serum hepcidin concentrations (+36.9%, P = 0.005). The increase of transferrin saturation levels persisted after 57 d of HDT bed rest (+13.5%, P = 0.026), suggesting that long-term exposure to microgravity sustainably increases serum iron availability in males, and consequently the risk of iron excess or misdistribution. In females, 6 and 57 d of HDT bed rest did not significantly change serum iron, transferrin saturation, or hepcidin levels. CONCLUSIONS: The data from this exploratory study suggest that 1) AG training does not influence the iron metabolism responses to microgravity; and 2) iron metabolism parameters, especially iron availability for cells, are significantly increased in males, but not in females, exposed to long-term simulated microgravity. Because of the small sample size of females, we nevertheless must be cautious before concluding that iron metabolism could differently respond to microgravity in females. This trial was registered at https://www.drks.de as DRKS00015677.

Visual Attention Relates to Operator Performance in Spacecraft Docking Training.

BACKGROUND: Manually controlled docking of a spacecraft to a space station is an operational task that poses high demands on cognitive and perceptual functioning. Effective processing of visual information is crucial for success. Eye tracking can reveal the operator's attentional focus unobtrusively and objectively. Therefore, our aim was to test the feasibility of eye tracking during a simulation of manual docking and to identify links between visual information processing and performance.METHODS: We hypothesized that duration and number of gazes to specific regions of interest of the simulation (total dwell time and number of dwells) would be associated with docking accuracy. Eye movements were recorded in 10 subjects (30% women, M = 33.4 yr old) during the 6° head-down tilt bed rest study AGBRESA during 20 training sessions with the 6df learning program for spacecraft docking.RESULTS: Subjects' gaze was directed most frequently and longest to the vizor (185 dwells and 22,355 ms per task) followed by the two instrument displays (together 75 dwells and 4048 ms per task). We observed a significant positive relationship between number and duration of visual checks of speed and distance to the docking point and the accuracy of the docking maneuver.DISCUSSION: In conclusion, eye tracking provides valuable information related to docking accuracy that might prospectively offer the opportunity to improve docking training effectiveness.Piechowski S, Johannes B, Pustowalow W, Arz M, Mulder E, Jordan J, Wolf OT, Rittweger J. Visual attention relates to operator performance in spacecraft docking training. Aerosp Med Hum Perform. 2022; 93(6):480-486.

The Effects of 30 Minutes of Artificial Gravity on Cognitive and Sensorimotor Performance in a Spaceflight Analog Environment.

The altered vestibular signaling and somatosensory unloading of microgravity result in sensory reweighting and adaptation to conflicting sensory inputs. Aftereffects of these adaptive changes are evident postflight as impairments in behaviors such as balance and gait. Microgravity also induces fluid shifts toward the head and an upward shift of the brain within the skull; these changes are well-replicated in strict head-down tilt bed rest (HDBR), a spaceflight analog environment. Artificial gravity (AG) is a potential countermeasure to mitigate these effects of microgravity. A previous study demonstrated that intermittent (six, 5-mins bouts per day) daily AG sessions were more efficacious at counteracting orthostatic intolerance in a 5 day HDBR study than continuous daily AG. Here we examined whether intermittent daily AG was also more effective than continuous dosing for mitigating brain and behavioral changes in response to 60 days of HDBR. Participants (n = 24) were split evenly between three groups. The first received 30 mins of continuous AG daily (cAG). The second received 30 mins of intermittent AG daily (6 bouts of 5 mins; iAG). The third received no AG (Ctrl). We collected a broad range of sensorimotor, cognitive, and brain structural and functional assessments before, during, and after the 60 days of HDBR. We observed no significant differences between the three groups in terms of HDBR-associated changes in cognition, balance, and functional mobility. Interestingly, the intermittent AG group reported less severe motion sickness symptoms than the continuous group during centrifugation; iAG motion sickness levels were not elevated above those of controls who did not undergo AG. They also had a shorter duration of post-AG illusory motion than cAG. Moreover, the two AG groups performed the paced auditory serial addition test weekly while undergoing AG; their performance was more accurate than that of controls, who performed the test while in HDBR. Although AG did not counteract HDBR-induced gait and balance declines, iAG did not cause motion sickness and was associated with better self-motion perception during AG ramp-down. Additionally, both AG groups had superior cognitive performance while undergoing AG relative to controls; this may reflect attention or motivation differences between the groups.

Head-Down-Tilt Bed Rest With Elevated CO2: Effects of a Pilot Spaceflight Analog on Neural Function and Performance During a Cognitive-Motor Dual Task.

Spaceflight has widespread effects on human performance, including on the ability to dual task. Here, we examine how a spaceflight analog comprising 30 days of head-down-tilt bed rest (HDBR) combined with 0.5% ambient CO2 (HDBR + CO2) influences performance and functional activity of the brain during single and dual tasking of a cognitive and a motor task. The addition of CO2 to HDBR is thought to better mimic the conditions aboard the International Space Station. Participants completed three tasks: (1) COUNT: counting the number of times an oddball stimulus was presented among distractors; (2) TAP: tapping one of two buttons in response to a visual cue; and (3) DUAL: performing both tasks concurrently. Eleven participants (six males) underwent functional MRI (fMRI) while performing these tasks at six time points: twice before HDBR + CO2, twice during HDBR + CO2, and twice after HDBR + CO2. Behavioral measures included reaction time, standard error of reaction time, and tapping accuracy during the TAP and DUAL tasks, and the dual task cost (DTCost) of each of these measures. We also quantified DTCost of fMRI brain activation. In our previous HDBR study of 13 participants (with atmospheric CO2), subjects experienced TAP accuracy improvements during bed rest, whereas TAP accuracy declined while in the current study of HDBR + CO2. In the HDBR + CO2 subjects, we identified a region in the superior frontal gyrus that showed decreased DTCost of brain activation while in HDBR + CO2, and recovered back to baseline levels before the completion of bed rest. Compared to HDBR alone, we found different patterns of brain activation change with HDBR + CO2. HDBR + CO2 subjects had increased DTCost in the middle temporal gyrus whereas HDBR subjects had decreased DTCost in the same area. Five of the HDBR + CO2 subjects developed signs of spaceflight-associated neuro-ocular syndrome (SANS). These subjects exhibited lower baseline dual task activation and higher slopes of change during HDBR + CO2 than subjects with no signs of SANS. Collectively, this pilot study provides insight into the additional and/or interactive effects of CO2 levels during HDBR, and information regarding the impacts of this spaceflight analog environment on the neural correlates of dual tasking.

Effects of long-term immobilisation on endomysium of the soleus muscle in humans.

NEW FINDINGS: What is the central question of this study? While muscle fibre atrophy in response to immobilisation has been extensively examined, intramuscular connective tissue, particularly endomysium, has been largely neglected: does endomysium content of the soleus muscle increase during bed rest? What is the main finding and its importance? Absolute endomysium content did not change, and previous studies reporting an increase are explicable by muscle fibre atrophy. It must be expected that even a relative connective tissue accumulation will lead to an increase in muscle stiffness. ABSTRACT: Muscle fibres atrophy during conditions of disuse. Whilst animal data suggest an increase in endomysium content with disuse, that information is not available for humans. We hypothesised that endomysium content increases during immobilisation. To test this hypothesis, biopsy samples of the soleus muscle obtained from 21 volunteers who underwent 60 days of bed rest were analysed using immunofluorescence-labelled laminin γ-1 to delineate individual muscle fibres as well as the endomysium space. The endomysium-to-fibre-area ratio (EFAr, as a percentage) was assessed as a measure related to stiffness, and the endomysium-to-fibre-number ratio (EFNr) was calculated to determine whether any increase in EFAr was absolute, or could be attributed to muscle fibre shrinkage. As expected, we found muscle fibre atrophy (P = 0.0031) that amounted to shrinkage by 16.6% (SD 28.2%) on day 55 of bed rest. ENAr increased on day 55 of bed rest (P < 0.001). However, when analysing EFNr, no effect of bed rest was found (P = 0.62). These results demonstrate that an increase in EFAr is likely to be a direct effect of muscle fibre atrophy. Based on the assumption that the total number of muscle fibres remains unchanged during 55 days of bed rest, this implies that the absolute amount of connective tissue in the soleus muscle remained unchanged. The increased relative endomysium content, however, could be functionally related to an increase in muscle stiffness.

Effects of Spaceflight Stressors on Brain Volume, Microstructure, and Intracranial Fluid Distribution.

Astronauts are exposed to elevated CO2 levels onboard the International Space Station. Here, we investigated structural brain changes in 11 participants following 30-days of head-down tilt bed rest (HDBR) combined with 0.5% ambient CO2 (HDBR + CO2) as a spaceflight analog. We contrasted brain changes observed in the HDBR + CO2 group with those of a previous HDBR sample not exposed to elevated CO2. Both groups exhibited a global upward shift of the brain and concomitant intracranial free water (FW) redistribution. Greater gray matter changes were seen in the HDBR + CO2 group in some regions. The HDBR + CO2 group showed significantly greater FW decrements in the posterior cerebellum and the cerebrum than the HDBR group. In comparison to the HDBR group, the HDBR + CO2 group exhibited greater diffusivity increases. In half of the participants, the HDBR + CO2 intervention resulted in signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), a constellation of ocular structural and functional changes seen in astronauts. We therefore conducted an exploratory comparison compared between subjects that did and did not develop SANS and found asymmetric lateral ventricle enlargement in the SANS group. These results enhance our understanding of the underlying mechanisms of spaceflight-induced brain changes, which is critical for promoting astronaut health and performance.

Visuomotor Adaptation Brain Changes During a Spaceflight Analog With Elevated Carbon Dioxide (CO2): A Pilot Study.

Astronauts on board the International Space Station (ISS) must adapt to several environmental challenges including microgravity, elevated carbon dioxide (CO2), and isolation while performing highly controlled movements with complex equipment. Head down tilt bed rest (HDBR) is an analog used to study spaceflight factors including body unloading and headward fluid shifts. We recently reported how HDBR with elevated CO2 (HDBR+CO2) affects visuomotor adaptation. Here we expand upon this work and examine the effects of HDBR+CO2 on brain activity during visuomotor adaptation. Eleven participants (34 ± 8 years) completed six functional MRI (fMRI) sessions pre-, during, and post-HDBR+CO2. During fMRI, participants completed a visuomotor adaptation task, divided into baseline, early, late and de-adaptation. Additionally, we compare brain activity between this NASA campaign (30-day HDBR+CO2) and a different campaign with a separate set of participants (60-day HDBR with normal atmospheric CO2 levels, n = 8; 34.25 ± 7.9 years) to characterize the specific effects of CO2. Participants were included by convenience. During early adaptation across the HDBR+CO2 intervention, participants showed decreasing activation in temporal and subcortical brain regions, followed by post- HDBR+CO2 recovery. During late adaptation, participants showed increasing activation in the right fusiform gyrus and right caudate nucleus during HDBR+CO2; this activation normalized to baseline levels after bed rest. There were no correlations between brain changes and adaptation performance changes from pre- to post HDBR+CO2. Also, there were no statistically significant differences between the HDBR+CO2 group and the HDBR controls, suggesting that changes in brain activity were due primarily to bed rest rather than elevated CO2. Five HDBR+CO2 participants presented with optic disc edema, a sign of Spaceflight Associated Neuro-ocular Syndrome (SANS). An exploratory analysis of HDBR+CO2 participants with and without signs of SANS revealed no group differences in brain activity during any phase of the adaptation task. Overall, these findings have implications for spaceflight missions and training, as ISS missions require individuals to adapt to altered sensory inputs over long periods in space. Further, this is the first study to verify the HDBR and elevated CO2 effects on the neural correlates of visuomotor adaptation.

Limited Effect of 60-Days Strict Head Down Tilt Bed Rest on Vascular Aging.

BACKGROUND: Cardiovascular risk may be increased in astronauts after long term space flights based on biomarkers indicating premature vascular aging. We tested the hypothesis that 60 days of strict 6° head down tilt bed rest (HDTBR), an established space analog, promotes vascular stiffening and that artificial gravity training ameliorates the response. METHODS: We studied 24 healthy participants (8 women, 24-55 years, BMI = 24.3 ± 2.1 kg/m2) before and at the end of 60 days HDTBR. 16 subjects were assigned to daily artificial gravity. We applied echocardiography to measure stroke volume and isovolumetric contraction time (ICT), calculated aortic compliance (stroke volume/aortic pulse pressure), and assessed aortic distensibility by MRI. Furthermore, we measured brachial-femoral pulse wave velocity (bfPWV) and pulse wave arrival times (PAT) in different vascular beds by blood pressure cuffs and photoplethysmography. We corrected PAT for ICT (cPAT). RESULTS: In the pooled sample, diastolic blood pressure (+8 ± 7 mmHg, p < 0.001), heart rate (+7 ± 9 bpm, p = 0.002) and ICT (+8 ± 13 ms, p = 0.036) increased during HDTBR. Stroke volume decreased by 14 ± 15 ml (p = 0.001). bfPWV, aortic compliance, aortic distensibility and all cPAT remained unchanged. Aortic area tended to increase (p = 0.05). None of the parameters showed significant interaction between HDTBR and artificial gravity training. CONCLUSION: 60 days HDTBR, while producing cardiovascular deconditioning and cephalad fluid shifts akin to weightlessness, did not worsen vascular stiffness. Artificial gravity training did not modulate the response.