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.

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.

Brain connectivity and behavioral changes in a spaceflight analog environment with elevated CO2.

Astronauts are exposed to microgravity and elevated CO2 levels onboard the International Space Station. Little is known about how microgravity and elevated CO2 combine to affect the brain and sensorimotor performance during and after spaceflight. Here we examined changes in resting-state functional connectivity (FC) and sensorimotor behavior associated with a spaceflight analog environment. Participants underwent 30 days of strict 6o head-down tilt bed rest with elevated ambient CO2 (HDBR+CO2). Resting-state functional magnetic resonance imaging and sensorimotor assessments were collected 13 and 7 days prior to bed rest, on days 7 and 29 of bed rest, and 0, 5, 12, and 13 days following bed rest. We assessed the time course of FC changes from before, during, to after HDBR+CO2. We then compared the observed connectivity changes with those of a HDBR control group that underwent HDBR in standard ambient air. Moreover, we assessed associations between post-HDBR+CO2 FC changes and alterations in sensorimotor performance. HDBR+CO2 was associated with significant changes in functional connectivity between vestibular, visual, somatosensory and motor brain areas. Several of these sensory and motor regions showed post-HDBR+CO2 FC changes that were significantly associated with alterations in sensorimotor performance. We propose that these FC changes reflect multisensory reweighting associated with adaptation to the HDBR+CO2 microgravity analog environment. This knowledge will further improve HDBR as a model of microgravity exposure and contribute to our knowledge of brain and performance changes during and after spaceflight.

The effects of a spaceflight analog with elevated CO2 on sensorimotor adaptation.

Aboard the International Space Station (ISS), astronauts must adapt to altered vestibular and somatosensory inputs due to microgravity. Sensorimotor adaptation on Earth is often studied with a task that introduces visuomotor conflict. Retention of the adaptation process, known as savings, can be measured when subjects are exposed to the same adaptive task multiple times. It is unclear how adaptation demands found on the ISS might interfere with the ability to adapt to other sensory conflict at the same time. In the present study, we investigated the impact of 30 days' head-down tilt bed rest combined with elevated carbon dioxide (HDBR + CO2) as a spaceflight analog on sensorimotor adaptation. Eleven subjects used a joystick to move a cursor to targets presented on a computer screen under veridical cursor feedback and 45° rotated feedback. During this NASA campaign, five individuals presented with optic disk edema, a sign of spaceflight-associated neuro-ocular syndrome (SANS). Thus, we also performed post hoc exploratory analyses between subgroups who did and did not show signs of SANS. HDBR + CO2 had some impact on sensorimotor adaptation, with a lack of savings across the whole group. SANS individuals showed larger, more persistent after-effects, suggesting a shift from relying on cognitive to more implicit processing of adaptive behaviors. Overall, these findings suggest that HDBR + CO2 alters the way in which individuals engage in sensorimotor processing. These findings have important implications for missions and mission training, which require individuals to adapt to altered sensory inputs over long periods in space.NEW & NOTEWORTHY This is the first bed rest campaign examining sensorimotor adaptation and savings in response to the combined effect of HDBR + CO2 and to observe signs of spaceflight-associated neuro-ocular syndrome (SANS) in HDBR participants. Our findings suggest that HDBR + CO2 alters the way that individuals engage in sensorimotor processing. Individuals who developed signs of SANS seem to rely more on implicit rather than cognitive processing of adaptive behaviors than subjects who did not present signs of SANS.

Ophthalmic changes in a spaceflight analog are associated with brain functional reorganization.

Following long-duration spaceflight, some astronauts exhibit ophthalmic structural changes referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. The origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. In the current spaceflight analog study, 11 subjects underwent 30 days of strict head down-tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2 ). Using functional magnetic resonance imaging (fMRI), we acquired resting-state fMRI data at 6 time points: before (2), during (2), and after (2) the HDBR+CO2 intervention. Five participants developed optic disc edema during the intervention (SANS subgroup) and 6 did not (NoSANS group). This occurrence allowed us to explore whether development of signs of SANS during the spaceflight analog impacted resting-state functional connectivity during HDBR+CO2 . In light of previous work identifying genetic and biochemical predictors of SANS, we further assessed whether the SANS and NoSANS subgroups exhibited differential patterns of resting-state functional connectivity prior to the HDBR+CO2 intervention. We found that the SANS and NoSANS subgroups exhibited distinct patterns of resting-state functional connectivity changes during HDBR+CO2 within visual and vestibular-related brain networks. The SANS and NoSANS subgroups also exhibited different resting-state functional connectivity prior to HDBR+CO2 within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration. We further present associations between functional connectivity within the identified networks and previously identified genetic and biochemical predictors of SANS. Subgroup differences in resting-state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the spaceflight analog. This finding suggests that SANS impacts not only neuro-ocular structures, but also functional brain organization. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences.

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.

Altered cerebral perfusion in response to chronic mild hypercapnia and head-down tilt Bed rest as an analog for Spaceflight.

PURPOSE: Following prolonged stays on the International Space Station (ISS), some astronauts exhibit visual acuity changes, ophthalmological findings, and mildly elevated intracranial pressures as part of a novel process called spaceflight-associated neuro-ocular syndrome (SANS). To determine the pathophysiology of SANS, NASA conducted a multi-investigator study in which 11 healthy participants underwent head-down tilt bed rest, mimicking microgravity-induced cephalad fluid shifts, combined with elevated ambient CO2 levels similar to those on the ISS (HDT+CO2). As part of that study, we examined the effects of HDT+CO2 on cerebral perfusion. METHODS: Using arterial spin labeling, we compared cerebral perfusion before, during, and after HDT+CO2 in participants who developed SANS (n = 5) with those who did not (n = 6). RESULTS: All participants demonstrated a decrease in perfusion during HDT+CO2 (mean decrease of 25.1% at HDT7 and 16.2% at HDT29); however, the timing and degree of change varied between the groups. At day 7 of HDT+CO2, the SANS group experienced a greater reduction in perfusion than the non-SANS group (p =.05, 95% CI:-0.19 to 16.11, d=.94, large effect). Conversely, by day 29 of HDT+CO2, the SANS group had significantly higher perfusion (approaching their baseline) than the non-SANS group (p = .04, 95% CI:0.33 to 13.07, d=1.01, large effect). CONCLUSION: Compared with baseline and recovery, HDT+CO2 resulted in reduced cerebral perfusion which varied based on SANS status. Further studies are needed to unravel the relative role of HDT vs hypercapnia, to determine if these perfusion changes are clinically relevant, and whether perfusion changes contribute to the development of SANS during spaceflight.

Daily 30-min exposure to artificial gravity during 60 days of bed rest does not maintain aerobic exercise capacity but mitigates some deteriorations of muscle function: results from the AGBRESA RCT.

PURPOSE: Spaceflight impairs physical capacity. Here we assessed the protective effect of artificial gravity (AG) on aerobic exercise capacity and muscle function during bed rest, a spaceflight analogue. METHODS: 24 participants (33 ± 9 years, 175 ± 9 cm, 74 ± 10 kg, 8 women) were randomly allocated to one of three groups: continuous AG (cAG), intermittent AG (iAG) or control (CTRL). All participants were subjected to 60 days of six-degree head-down tilt bed rest, and subjects of the intervention groups completed 30 min of centrifugation per day: cAG continuously and iAG for 6 × 5 min, with an acceleration of 1g at the center of mass. Physical capacity was assessed before and after bed rest via maximal voluntary contractions, cycling spiroergometry, and countermovement jumps. RESULTS: AG had no significant effect on aerobic exercise capacity, flexor muscle function and isometric knee extension strength or rate of force development (RFD). However, AG mitigated the effects of bed rest on jumping power (group * time interaction of the rmANOVA p < 0.001; iAG - 25%, cAG - 26%, CTRL - 33%), plantar flexion strength (group * time p = 0.003; iAG - 35%, cAG - 31%, CTRL - 48%) and plantar flexion RFD (group * time p = 0.020; iAG - 28%, cAG - 12%, CTRL - 40%). Women showed more pronounced losses than men in jumping power (p < 0.001) and knee extension strength (p = 0.010). CONCLUSION: The AG protocols were not suitable to maintain aerobic exercise capacity, probably due to the very low cardiorespiratory demand of this intervention. However, they mitigated some losses in muscle function, potentially due to the low-intensity muscle contractions during centrifugation used to avoid presyncope.

Effect of novel short-arm human centrifugation-induced gravitational gradients upon cardiovascular responses, cerebral perfusion and g-tolerance.

KEY POINTS: The aim of this study was to determine the effect of rotational axis position (RAP and thus g-gradient) during short-arm human centrifugation (SAHC) upon cardiovascular responses, cerebral perfusion and g-tolerance. In 10 male and 10 female participants, 10 min passive SAHC runs were performed with the RAP above the head (P1), at the apex of the head (P2), or at heart level (P3), with foot-level Gz at 1.0 g, 1.7 g and 2.4 g. We hypothesized that movement of the RAP from above the head (the conventional position) towards the heart might reduce central hypovolaemia, limit cardiovascular responses, aid cerebral perfusion, and thus promote g-tolerance. Moving the RAP footward towards the heart decreased the cerebral tissue saturation index, calf circumference and heart rate responses to SAHC, thereby promoting g-tolerance. Our results also suggest that RAP, and thus g-gradient, warrants further investigation as it may support use as a holistic spaceflight countermeasure. ABSTRACT: Artificial gravity (AG) through short-arm human centrifugation (SAHC) has been proposed as a holistic spaceflight countermeasure. Movement of the rotational axis position (RAP) from above the head towards the heart may reduce central hypovolaemia, aid cerebral perfusion, and thus promote g-tolerance. This study determined the effect of RAP upon cardiovascular responses, peripheral blood displacement (i.e. central hypovolaemia), cerebral perfusion and g-tolerance, and their inter-relationships. Twenty (10 male) healthy participants (26.2 ± 4.0 years) underwent nine (following a familiarization run) randomized 10 min passive SAHC runs with RAP set above the head (P1), at the apex of the head (P2), or at heart level (P3) with foot-level Gz at 1.0 g, 1.7 g and 2.4 g. Cerebral tissue saturation index (cTSI, cerebral perfusion surrogate), calf circumference (CC, central hypovolaemia), heart rate (HR) and digital heart-level mean arterial blood pressure (MAP) were continuously recorded, in addition to incidence of pre-syncopal symptoms (PSS). ΔCC and ΔHR increases were attenuated from P1 to P3 (ΔCC: 5.46 ± 0.54 mm to 2.23 ± 0.42 mm; ΔHR: 50 ± 4 bpm to 8 ± 2 bpm, P < 0.05). In addition, ΔcTSI decrements were also attenuated (ΔcTSI: -2.85 ± 0.48% to -0.95 ± 0.34%, P < 0.05) and PSS incidence lower in P3 than P1 (P < 0.05). A positive linear relationship was observed between ΔCC and ΔHR with increasing +Gz, and a negative relationship between ΔCC and ΔcTSI, both independent of RAP. Our data suggest that movement of RAP towards the heart (reduced g-gradient), independent of foot-level Gz, leads to improved g-tolerance. Further investigations are required to assess the effect of differential baroreceptor feedback (i.e. aortic-carotid g-gradient).

Unchanged cerebrovascular CO2 reactivity and hypercapnic ventilatory response during strict head-down tilt bed rest in a mild hypercapnic environment.

KEY POINTS: Carbon dioxide levels are mildly elevated on the International Space Station and it is unknown whether this chronic exposure causes physiological changes to astronauts. We combined ∼4 mmHg ambient PCO2 with the strict head-down tilt bed rest model of spaceflight and this led to the development of optic disc oedema in one-half of the subjects. We demonstrate no change in arterialized PCO2 , cerebrovascular reactivity to CO2 or the hypercapnic ventilatory response. Our data suggest that the mild hypercapnic environment does not contribute to the development of spaceflight associated neuro-ocular syndrome. ABSTRACT: Chronically elevated carbon dioxide (CO2 ) levels can occur in confined spaces such as the International Space Station. Using the spaceflight analogue 30 days of strict 6° head-down tilt bed rest (HDTBR) in a mild hypercapnic environment ( PCO2 = ∼4 mmHg), we investigated arterialized PCO2 , cerebrovascular reactivity and the hypercapnic ventilatory response in 11 healthy subjects (five females) before, on days 1, 9, 15 and 30 of bed rest (BR), and 6 and 13 days after HDTBR. During all HDTBR time points, arterialized PCO2 was not significantly different from the pre-HDTBR measured in the 6° HDT posture, with a mean (95% confidence interval) increase of 1.2 mmHg (-0.2 to 2.5 mmHg, P = 0.122) on day 30 of HDTBR. Respiratory acidosis was never detected, although a mild metabolic alkalosis developed on day 30 of HDTBR by a mean (95% confidence interval) pH change of 0.032 (0.022-0.043; P < 0.001), which remained elevated by 0.021 (0.011-0.031; P < 0.001) 6 days after HDTBR. Arterialized pH returned to pre-HDTBR levels 13 days after BR with a change of -0.001 (-0.009 to 0.007; P = 0.991). Compared to pre-HDTBR, cerebrovascular reactivity during and after HDTBR did not change. Baseline ventilation, ventilatory recruitment threshold and the slope of the ventilatory response were similar between pre-HDTBR and all other time points. Taken together, these data suggest that the mildly increased ambient PCO2 combined with 30 days of strict 6° HDTBR did not change arterialized PCO2 levels. Therefore, the experimental conditions were not sufficient to elicit a detectable physiological response.

Effects of 21 days of bed rest and whey protein supplementation on plantar flexor muscle fatigue resistance during repeated shortening contractions.

PURPOSE: Space flight and bed rest (BR) lead to a rapid decline in exercise capacity. Whey protein plus potassium bicarbonate diet-supplementation (NUTR) could attenuate this effect by improving oxidative metabolism. We evaluated the impact of 21-day BR and NUTR on fatigue resistance of plantar flexor muscles (PF) during repeated shortening contractions, and whether any change was related to altered energy metabolism and muscle oxygenation. METHODS: Ten healthy men received a standardized isocaloric diet with (n = 5) or without (n = 5) NUTR. Eight bouts of 24 concentric plantar flexions (30 s each bout) with 20 s rest between bouts were employed. PF muscle size was assessed by means of peripheral quantitative computed tomography. PF muscle volume was assessed with magnetic resonance imaging. PF muscle force, contraction velocity, power and surface electromyogram signals were recorded during each contraction, as well as energy metabolism (31P nuclear magnetic resonance spectroscopy) and oxygenation (near-infrared spectroscopy). Cardiopulmonary parameters were measured during an incremental cycle exercise test. RESULTS: BR caused 10-15% loss of PF volume that was partly recovered 3 days after re-ambulation, as a consequence of fluid redistribution. Unexpectedly, PF fatigue resistance was not affected by BR or NUTR. BR induced a shift in muscle metabolism toward glycolysis and some signs of impaired muscle oxygen extraction. NUTR did not attenuate the BR-induced-shift in energy metabolism. CONCLUSIONS: Twenty-one days' BR did not impair PF fatigue resistance, but the shift to glycolytic metabolism and indications of impaired oxygen extraction may be early signs of developing reduced muscle fatigue resistance.

Influence of bed rest on plasma galanin and adrenomedullin at presyncope.

BACKGROUND: The role of hormones in reduced orthostatic tolerance following long-term immobilization remains uncertain. We have previously shown that plasma concentrations of adrenomedullin and galanin, two peptides with vasodepressor properties, rise significantly during orthostatic challenge. We tested the hypothesis that bedrest immobilization increases the rise in adrenomedullin and galanin during orthostatic challenge leading to presyncope. MATERIALS AND METHODS: We measured baseline (supine), presyncope and recovery (10 min postpresyncope, supine) levels of adrenomedullin and galanin in 8 healthy men, before and after 21 days of -6° head-down bed rest (HDBR). Presyncope was elicited using a combined head-up tilt and graded lower body negative pressure protocol. Orthostatic tolerance was defined as the time taken from the commencement of head-up tilt to the development of presyncope. RESULTS: Orthostatic tolerance time after HDBR reduced by 8·36 ± 5·39 min (P = 0·0032). HDBR increased plasma adrenomedullin concentration to orthostatic challenge (P = 0·0367). Compared to pre-HDBR, a significant rise in post-HDBR presyncopal (P < 0·001) and recovery adrenomedullin concentration (P < 0·01) was demonstrated. In contrast, we observed no change in pre- and post-HDBR galanin levels to orthostatic challenge. CONCLUSIONS: Bedrest immobilization appears to affect adrenomedullin levels in that greater increases in adrenomedullin occur at presyncope following bedrest immobilization. Due to its peripheral vasculature hypotensive effect, the greater levels of adrenomedullin at presyncope following bedrest immobilization may have contributed to the reduced orthostatic capacity postbedrest.

Microgravity Simulated by the 6° Head-Down Tilt Bed Rest Test Increases Intestinal Motility but Fails to Induce Gastrointestinal Symptoms of Space Motion Sickness.

BACKGROUND: Space motion sickness (SMS) is the most relevant medical problem during the first days in microgravity. Studies addressing pathophysiology in space face severe technical challenges and microgravity is frequently simulated using the 6° head-down tilt bed rest test (HDT). AIM: We were aiming to test whether SMS could be simulated by HDT, identify related changes in gastrointestinal physiology and test for beneficial effects of exercise interventions. METHODS: HDT was performed in ten healthy individuals. Each individual was tested in three study campaigns varying by a 30-min daily exercise intervention of either standing, an upright exercise regimen, or no intervention. Gastrointestinal symptoms, stool characteristics, gastric emptying time, and small intestinal transit were assessed using standardized questionnaires, (13)C octanoate breath test, and H2 lactulose breath test, respectively, before and at day 2 and 5 of HDT. RESULTS: Individuals described no or minimal gastrointestinal symptoms during HDT. Gastric emptying remained unchanged relative to baseline data collection (BDC). At day 2 of HDT the H2 peak of the lactulose test appeared earlier (mean ± standard error for BDC-1, HDT2, HDT5: 198 ± 7, 139 ± 18, 183 ± 10 min; p: 0.040), indicating accelerated small intestinal transit. Furthermore, during HDT, stool was softer and stool mass increased (BDC: 47 ± 6, HDT: 91 ± 12, recovery: 53 ± 8 g/day; p: 0.014), indicating accelerated colonic transit. Exercise interventions had no effect. CONCLUSION: HDT did not induce symptoms of SMS. During HDT, gastric emptying remained unchanged, but small and large intestinal transit was accelerated.

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.

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.

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.

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.

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.

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.