Six-day dry immersion leads to downregulation of slow-fiber type and mitochondria-related genes expression.

The soleus muscle in humans is responsible for maintaining an upright posture and participating in walking and running. Under muscle disuse, it undergoes molecular signaling changes that result in altered force and work capacity. The triggering mechanisms and pathways of these changes are not yet fully understood. In this article, we aimed to detect the molecular pathways that are involved in the unloading-induced alterations in the human soleus muscle under 6-days of dry immersion. A 6-day dry immersion led to the downregulation of mitochondrial biogenesis and dynamics markers, upregulation of calcium-dependent CaMK II phosphorylation, enhanced PGC1α promoter region methylation, and altered muscle micro-RNA expression, without affecting p-AMPK content or fiber-type transformation.NEW & NOTEWORTHY Dry immersion dysregulates mitochondrial genes expression, affects mi-RNA expression and PGC1 promoter methylation.

Corticospinal excitability after 5-day Dry Immersion in women.

In light of the development of manned astronautics and the increasing participation of women in space flights, the question of female body adaptation to microgravity conditions becomes relevant. Currently, one of the important directions in this issue is to study the effects of support withdrawal as a factor of weightlessness on the human sensorimotor system. Dry Immersion is one of the well-known ground-based models, which adequately reproduces the main physiological effects of space flight. The aim of this study was to evaluate the changes in motor evoked potentials of the lower leg gravity-dependent muscles in women after a 5-day Dry Immersion. We analyzed evoked responses to transcranial and trans-spinal magnetic stimulation. In this method, areas of interest (the motor cortex and lumbosacral thickening of the spinal cord) are stimulated with an electromagnetic stimulus. The experiment was conducted with the participation of 16 healthy female volunteers with a natural menstrual cycle. The thresholds, amplitudes, and latencies of motor potentials evoked by magnetic stimulation were assessed. We showed that 5-day exposure to support withdrawal leads to a decrease in motor-evoked potential thresholds and central motor conduction time, although changes in motor response amplitudes were ambiguous. The data obtained correspond to the results of previous research on Dry Immersion effects on the sensorimotor system in men.

Corrigendum: Impact of different ground-based microgravity models on human sensorimotor system.

[This corrects the article DOI: 10.3389/fphys.2023.1085545.].

Sensory organization of postural control after long term space flight.

Background: Alterations in motor control systems is an inevitable consequence of space flights of any duration. After the flight, the crew-members have significant difficulties with maintaining upright balance and locomotion, which last several days following landing. At the same time, the specific mechanisms of these effects remain unclear. Objectives: The aim of the study was to assess effects of long-term space flight on postural control and to define the changes of sensory organization caused by microgravity. Methods: 33 cosmonauts of Russian Space Agency, the members of International Space Station (ISS) flights of duration between 166 and 196 days took part in this study. Computerized Dynamic Posturography (CDP) tests, which include assessment of visual, proprioceptive and vestibular function in postural stability, was performed twice before the flight and on the 3rd, 7th, and 10th days after landing. The video analysis of ankle and hip joints fluctuations was performed to investigate the basis of postural changes. Results: Exposure to long-term space flight was followed by considerable changes of postural stability (-27% of Equilibrium Score value in the most complicated test, SOT5m). Changes in postural strategies to maintain balance were observed in the tests which provide the challenge for vestibular system. In particular, increased hip joint involvement (+100% in median value and +135% in 3rd quartile of hip angle fluctuation RMS in SOT5m) into postural control process was revealed. Conclusion: Decrease of postural stability after long-term space flight was associated with alterations in vestibular system and biomechanically was revealed by increased hip strategy which is less accurate, but simpler in terms of the central control.

Perception of length and orientation in dry immersion.

Introduction: How does gravity (or lack thereof) affect sensory-motor processing? We analyze sensorimotor estimation dynamics for line segments with varying direction (orientation) in a 7-day dry immersion (DI), a ground-based model of gravitational unloading. Methods: The measurements were carried out before the start of the DI, on the first, third, fifth and seventh days of the DI, and after its completion. At the memorization stage, the volunteers led the leading hand along the visible segment on a touchscreen display, and at the reproduction stage they repeated this movement on an empty screen. A control group followed the same procedure without DI. Results: Both in the DI and control groups, when memorizing, the overall error in estimating the lengths and directions of the segments was small and did not have pronounced dynamics; when reproducing, an oblique effect (higher variability of responses to oblique orientations compared to cardinal ones) was obtained. We then separated biases (systematic error) and uncertainty (random error) in subjects' responses. At the same time, two opposite trends were more pronounced in the DI group during the DI. On the one hand the cardinal bias (a repulsion of orientation estimates away from cardinal axes) and, to a small extent, the variability of direction estimates decreased. On the other hand, the overestimation bias in length estimates increased. Discussion: Such error pattern strongly supports the hypotheses of the vector encoding, in which the direction and length of the planned movement are encoded independently of each other when the DI disrupts primarily the movement length encoding.

Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after 3-day dry immersion.

We aimed to explore the effect of the 3-day dry immersion, a model of physical unloading, on mitochondrial function, transcriptomic and proteomic profiles in a slow-twitch soleus muscle of six healthy females. We registered that a marked reduction (25-34%) in the ADP-stimulated respiration in permeabilized muscle fibers was not accompanied by a decrease in the content of mitochondrial enzymes (mass spectrometry-based quantitative proteomics), hence, it is related to the disruption in regulation of respiration. We detected a widespread change in the transcriptomic profile (RNA-seq) upon dry immersion. Downregulated mRNAs were strongly associated with mitochondrial function, as well as with lipid metabolism, glycolysis, insulin signaling, and various transporters. Despite the substantial transcriptomic response, we found no effect on the content of highly abundant proteins (sarcomeric, mitochondrial, chaperon, and extracellular matrix-related, etc.) that may be explained by long half-life of these proteins. We suggest that during short-term disuse the content of some regulatory (and usually low abundant) proteins such as cytokines, receptors, transporters, and transcription regulators is largely determined by their mRNA concentration. These mRNAs revealed in our work may serve as putative targets for future studies aimed at developing approaches for the prevention of muscle deconditioning induced by disuse.NEW & NOTEWORTHY Three-day dry immersion (a model of physical unloading) substantially changes the transcriptomic profile in the human soleus muscle, a muscle with predominantly slow-twitch fibers and strong postural function; despite this, we found no effect on the muscle proteome (highly abundant proteins). Dry immersion markedly reduces ADP-stimulated respiration; this decline is not accompanied by a decrease in the content of mitochondrial proteins/respiratory enzymes, indicating the disruption in regulation of cellular respiration.

Impact of different ground-based microgravity models on human sensorimotor system.

This review includes current and updated information about various ground-based microgravity models and their impact on the human sensorimotor system. All known models of microgravity are imperfect in a simulation of the physiological effects of microgravity but have their advantages and disadvantages. This review points out that understanding the role of gravity in motion control requires consideration of data from different environments and in various contexts. The compiled information can be helpful to researchers to effectively plan experiments using ground-based models of the effects of space flight, depending on the problem posed.

Prolonged microgravity induces reversible and persistent changes on human cerebral connectivity.

The prospect of continued manned space missions warrants an in-depth understanding of how prolonged microgravity affects the human brain. Functional magnetic resonance imaging (fMRI) can pinpoint changes reflecting adaptive neuroplasticity across time. We acquired resting-state fMRI data of cosmonauts before, shortly after, and eight months after spaceflight as a follow-up to assess global connectivity changes over time. Our results show persisting connectivity decreases in posterior cingulate cortex and thalamus and persisting increases in the right angular gyrus. Connectivity in the bilateral insular cortex decreased after spaceflight, which reversed at follow-up. No significant connectivity changes across eight months were found in a matched control group. Overall, we show that altered gravitational environments influence functional connectivity longitudinally in multimodal brain hubs, reflecting adaptations to unfamiliar and conflicting sensory input in microgravity. These results provide insights into brain functional modifications occurring during spaceflight, and their further development when back on Earth.

Dry immersion induced acute low back pain and its relationship with trunk myofascial viscoelastic changes.

Microgravity induces spinal elongation and Low Back Pain (LBP) but the pathophysiology is unknown. Changes in paraspinal muscle viscoelastic properties may play a role. Dry Immersion (DI) is a ground-based microgravity analogue that induces changes in m. erector spinae superficial myofascial tissue tone within 2 h. This study sought to determine whether bilateral m. erector spinae tone, creep, and stiffness persist beyond 2 h; and if such changes correlate with DI-induced spinal elongation and/or LBP. Ten healthy males lay in the DI bath at the Institute of Biomedical Problems (Moscow, Russia) for 6 h. Bilateral lumbar (L1, L4) and thoracic (T11, T9) trunk myofascial tone, stiffness and creep (MyotonPRO), and subjective LBP (0-10 NRS) were recorded before DI, after 1h, 6 h of DI, and 30min post. The non-standing spinal length was evaluated on the bath lifting platform using a bespoke stadiometer before and following DI. DI significantly modulated m. erector spinae viscoelastic properties at L4, L1, T11, and T9 with no effect of laterality. Bilateral tissue tone was significantly reduced after 1 and 6 h DI at L4, L1, T11, and T9 to a similar extent. Stiffness was also reduced by DI at 1 h but partially recovered at 6 h for L4, L1, and T11. Creep was increased by DI at 1 h, with partial recovery at 6 h, although only T11 was significant. All properties returned to baseline 30 min following DI. Significant spinal elongation (1.17 ± 0.20 cm) with mild (at 1 h) to moderate (at 6 h) LBP was induced, mainly in the upper lumbar and lower thoracic regions. Spinal length increases positively correlated (Rho = 0.847, p = 0.024) with middle thoracic (T9) tone reduction, but with no other stiffness or creep changes. Spinal length positively correlated (Rho = 0.557, p = 0.039) with Max LBP; LBP failed to correlate with any m. erector spinae measured parameters. The DI-induced bilateral m. erector spinae tone, creep, and stiffness changes persist beyond 2 h. Evidence of spinal elongation and LBP allows suggesting that the trunk myofascial tissue changes could play a role in LBP pathogenesis observed in real and simulated microgravity. Further study is warranted with longer duration DI, assessment of IVD geometry, and vertebral column stability.

Multiple field tests on landing day: Early mobility may improve postural recovery following spaceflight.

Adaptation to microgravity causes astronauts to experience sensorimotor disturbances during return to Earth leading to functional difficulties. Recently, the Field Test (FT) study involving an incrementally demanding sensorimotor functional test battery has allowed for an unprecedented view into early decrements and recovery from multiple tests conducted on the landing day following 6-months International Space Station missions. Although the protocol was challenging and temporarily increased motion sickness symptoms, there were anecdotal reports that performing these tasks within the first few hours of landing accelerated their recovery. Therefore, results from computerized dynamic posturography (CDP) following return to Houston were used to compare recovery between crewmembers that participated in FT (n = 18) with those that did not (controls, n = 11). While there were significant decrements in postural performance for both groups, some FT participants tended to perform closer to their preflight baseline in the most challenging condition of the CDP sensitive to vestibular function-eyes closed, unstable support and head movements. However, the distribution of difference scores appeared bimodal with other FT participants in the lower range of performance. We attribute these observations to the manner in which the field tests were implemented-some benefitted by encouraging early movement to drive adaptation when performed in a constrained incremental fashion; however, movements above aversive thresholds may have impaired adaptation in others. Challenging the sensorimotor system with increasingly provocative movements performed as close to landing as possible, as long as within individual thresholds, could be a useful intervention to accelerate astronaut's sensorimotor readaptation that deserves further study.

Effect of Modulated Electromyostimulation on the Motor System of Elderly Neurological Patients. Pilot Study of Russian Currents Also Known as Kotz Currents.

In this brief report, we present preliminary findings from a study of the use of electromyostimulation (EMS) in neurological patients. Assuming the approach to be sufficiently effective, we decided to investigate the motor system of elderly neurological patients before and after a course of Russian currents EMS, which were developed for Soviet athletes and cosmonauts. To this point, 19 patients-EMS (n = 11) and control (n = 8)-have successfully completed the study. The study included patients aged 60-90 years with confirmed walking and balance disorders with a history of chronic cerebral ischemia. Patients in the experimental group underwent a course of modulated EMS of the hip and shin muscles from 3 to 9 procedures. Preliminary results of the study showed good patient acceptance of EMS. After the course, the EMS group showed a significant improvement from baseline in the Tinetti Test (+1.4 points, p = 0.0045), Rivermead Mobility Index (+0.5 points, p = 0.0022), and Timed Up and Go Test (-1.2 s, p = 0.0053). There was also a significant improvement in balance quality of 8.6% (p = 0.04). Shin muscle strength, although trending positively, did not change significantly. There was also no change in hip and shin muscles' tone. No significant changes were observed in the control group in the same tests. It can be concluded that stimulation of the hip and shin muscles with Russian (Kotz) currents has a positive effect on the motor system of elderly neurological patients. Significant effects with a course of short duration indicate that this EMS regimen is promising.

Application of Space Technologies Aimed at Proprioceptive Correction in Terrestrial Medicine in Russia.

Space technologies greatly contributed not only to space medicine but also to terrestrial medicine, which actively involves these technologies in everyday practice. Based on the existing countermeasures, and due to similarities of sensorimotor alterations provoked by the weightlessness with various neurological disorders, a lot of work has been dedicated to adaptation and introduction of these countermeasures for rehabilitation of patients. Axial loading suit and mechanical stimulation of the soles' support zones are used in mitigation of stroke and traumatic brain injury consequences. They are also applied for rehabilitation of children with cerebral palsy. Complex application of these proprioceptive correction methods in neurorehabilitation programs makes it possible to effectively treat neurological patients with severe motor disturbances and significant brain damage.

In-hospital electrical muscle stimulation for patients early after heart failure decompensation: results from a prospective randomised controlled pilot trial.

BACKGROUND: Electrical muscle stimulation (EMS) is being evaluated as a possible alternative to exercise training to improve functional capacity in severely deconditioned patients with heart failure (HF). However, there is insufficient data on delayed effects of EMS starting early after decompensation. The aim of this study was to determine the impact of a short inpatient EMS intervention in severely deconditioned patients with HF on functional capacity and quality of life (QoL) over a follow-up period of 1 month. METHODS: This is a prospective randomised sham-controlled pilot study. 45 patients hospitalised for decompensated systolic HF (58% men, mean age 66.4±10.2 years) were randomised to EMS (n=22) or sham stimulation (n=23) of lower limbs starting within 3 days after admission. The intervention included 7-10 sessions lasting from 30 to 90 min. The 6-minute walking test distance (6-MWTD), Duke Activity Status Index (DASI) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were evaluated at baseline, discharge and after 1 month. RESULTS: All patients completed the programme with good EMS tolerance. 37 patients were included in the final analysis. At discharge, 6-MWTD improved from 206,1±61,3 to 299.5±91 m, DASI from 12.1±5.6 to 18.3±7.2 and MLHFQ from 55.6±8.5 to 34.2±9 with EMS compared with smaller improvements in the sham group (p<0.05 for all). One month after discharge, improvements in the EMS group remained significant for MLHFQ (p=0.004) and DASI (p=0.042) and statistically non-significant for 6-MWTD compared with the sham group. CONCLUSIONS: Short-term in-hospital EMS leads to improvements in functional capacity and QoL in selected patients early after HF decompensation that are retained over 1 month after discharge and therefore may serve as initial intervention to improve physical capacity or as a bridge to further conventional exercise training. Larger studies are required to evaluate individual responses to an early initiation of EMS in decompensated HF as well as long-term effects.

The effect of prolonged spaceflight on cerebrospinal fluid and perivascular spaces of astronauts and cosmonauts.

Long-duration spaceflight induces changes to the brain and cerebrospinal fluid compartments and visual acuity problems known as spaceflight-associated neuro-ocular syndrome (SANS). The clinical relevance of these changes and whether they equally affect crews of different space agencies remain unknown. We used MRI to analyze the alterations occurring in the perivascular spaces (PVS) in NASA and European Space Agency astronauts and Roscosmos cosmonauts after a 6-mo spaceflight on the International Space Station (ISS). We found increased volume of basal ganglia PVS and white matter PVS (WM-PVS) after spaceflight, which was more prominent in the NASA crew than the Roscosmos crew. Moreover, both crews demonstrated a similar degree of lateral ventricle enlargement and decreased subarachnoid space at the vertex, which was correlated with WM-PVS enlargement. As all crews experienced the same environment aboard the ISS, the differences in WM-PVS enlargement may have been due to, among other factors, differences in the use of countermeasures and high-resistive exercise regimes, which can influence brain fluid redistribution. Moreover, NASA astronauts who developed SANS had greater pre- and postflight WM-PVS volumes than those unaffected. These results provide evidence for a potential link between WM-PVS fluid and SANS.

Brain Connectometry Changes in Space Travelers After Long-Duration Spaceflight.

Humans undergo extreme physiological changes when subjected to long periods of weightlessness, and as we continue to become a space-faring species, it is imperative that we fully understand the physiological changes that occur in the human body, including the brain. In this study, we present findings of brain structural changes associated with long-duration spaceflight based on diffusion magnetic resonance imaging (dMRI) data. Twelve cosmonauts who spent an average of six months aboard the International Space Station (ISS) were scanned in an MRI scanner pre-flight, ten days after flight, and at a follow-up time point seven months after flight. We performed differential tractography, a technique that confines white matter fiber tracking to voxels showing microstructural changes. We found significant microstructural changes in several large white matter tracts, such as the corpus callosum, arcuate fasciculus, corticospinal, corticostriatal, and cerebellar tracts. This is the first paper to use fiber tractography to investigate which specific tracts exhibit structural changes after long-duration spaceflight and may direct future research to investigate brain functional and behavioral changes associated with these white matter pathways.

NAIAD-2020: Characteristics of Motor Evoked Potentials After 3-Day Exposure to Dry Immersion in Women.

As female astronauts participate in space flight more and more frequently, there is a demand for research on how the female body adapts to the microgravity environment. In particular, there is very little research on how the neuromuscular system reacts to gravitational unloading in women. We aimed to estimate changes in motor evoked potentials (MEPs) in the lower leg muscles in women after 3-day exposure to Dry Immersion (DI), which is one of the most widely used ground models of microgravity. Six healthy female volunteers (mean age 30.17 ± 5.5 years) with a natural menstrual cycle participated in this experiment. MEPs were recorded from the gastrocnemius and soleus muscles twice before DI, on the day of DI completion, and 3 days after DI, during the recovery period. To evoke motor responses, transcranial and trans-spinal magnetic stimulation was applied. We showed that changes in MEP characteristics after DI exposure were different depending on the stimulation site, but were similar for both muscles. For trans-spinal stimulation, MEP thresholds decreased compared to baseline values, and amplitudes, on the contrary, increased, resembling the phenomenon of hypogravitational hyperreflexia. This finding is in line with data observed in other experiments on both male and female participants. MEPs to transcranial stimulation had an opposing dynamic, which may have resulted from the small group size and large inter-subject variability, or from hormonal fluctuations during the menstrual cycle. Central motor conduction time remained unchanged, suggesting that pyramidal tract conductibility was not affected by DI exposure. More research is needed to explore the underlying mechanisms.

Sleep in 21-Day Dry Immersion. Are Cardiovascular Adjustments Rapid Eye Movement Sleep-Dependent?

Introduction: A decrease in sleep quality and duration during space missions has repeatedly been reported. However, the exact causes that underlie this effect remain unclear. In space, sleep might be impacted by weightlessness and its influence on cardiovascular function. In this study, we aimed at exploring the changes of night sleep architecture during prolonged, 21-day Dry Immersion (DI) as one of the ground-based models for microgravity studies and comparing them with adaptive changes in the cardiovascular system. Methods: Ten healthy young men were exposed to DI for 21 days. The day before (baseline, B-1), on the 3rd (DI3), 10th (DI10), and 19th (DI19) day of DI, as well as in the recovery period, 1 day after the end of DI (R + 1), they were subjected to overnight polysomnography (PSG) and ambulatory blood pressure monitoring. Results: On DI3, when the most severe back pain occurred due to the effects of DI on the spine and back muscles, the PSG data showed dramatically disorganized sleep architecture. Sleep latency, the number of awakenings, and the duration of wake after sleep onset (WASO) were significantly increased compared with the B-1. Furthermore, the sleep efficiency, duration of rapid eye movement sleep (REM), and duration of non-rapid eye movement stage 2 decreased. On DI10, subjective pain ratings declined to 0 and sleep architecture returned to the baseline values. On DI19, the REM duration increased and continued to rise on R + 1. An increase in REM was accompanied by rising in a nighttime heart rate (HR), which also shows the most significant changes after the end of DI. On DI19 and R + 1, the REM duration showed opposite correlations with the BP parameters: on DI19 it was negatively associated with the systolic BP (SBP), and on R + 1 it was positively correlated with the diastolic BP (DBP). Conclusion: An increase in REM at the end of DI and in recovery might be associated with regulatory changes in the cardiovascular system, in particular, with the reorganization of the peripheral and central blood flow in response to environmental changes.

Real-world experience of feasibility and efficacy of electrical muscle stimulation in elderly patients with acute heart failure: A randomized controlled study.

BACKGROUND: Reduced aerobic capacity and deconditioning contributes to morbidity and mortality in elderly acute heart failure (AHF) patients. Electrical muscle stimulation (EMS) has shown to be a suitable alternative to exercise in AHF. However, feasibility and efficacy are unknown in a real-world setting. METHODS: This is a prospective, open label blinded, randomized, controlled study, investigating feasibility and efficacy of high-intensity versus low-intensity EMS versus controls in elderly AHF patients. Patients and investigators were blinded to the intervention. EMS was offered to > 60 years old AHF patients, initiated during hospitalization and continued at home. Outcome measures included changes in 6-min walking test distance (6-MWTD), functional capacity and quality-of-life at 3 and 6 weeks. RESULTS: Among 97 consecutive AHF patients (78.1 ± 9.4 years, 42.3% females), 60 (61.9%) were eligible for EMS. Of these, 27 provided written informed consent and were randomly assigned to high-intensity (n = 10), low-intensity EMS (n = 9) and controls (n = 8). 13/27 completed the intervention. Main reason for dropouts was intolerance of the overall intervention burden. MACE occurred in 5 and were not associated with the study. EMS groups showed significant improvement of 6-MWTD (controls vs low-intensity p = 0.018) and of independence in daily living (for both p < 0.05). CONCLUSIONS: Changes in 6-MWTD suggest efficacy of EMS. Whereas all tolerated EMS well, the burden of study intervention was too high and resulted in a consent rate of <50% and high dropouts, which limit the interpretability of our data. Less demanding EMS protocols are required to evaluate the full potential of EMS in elderly AHF patients.