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Abstract The aim of this study was to analyze the mechanisms of the development of hypogravitational hyperreflexia in the motoneuron pool of gravity-dependent muscles such as the gastrocnemius and soleus muscles of the leg under the conditions of five-day “dry” immersion in healthy volunteers using the method of transcranial and trans-spinal magnetic stimulation. The essence of the method lies in the stimulation of the areas of interest (motor areas of the cerebral cortex and lumbosacral thickening) with an electromagnetic stimulus. The study involved 10 subjects at the age of 29.9 ± 6.9 years, with no history of movement disorders or neurological diseases. The excitability of the motor neuron pool in both muscles was judged by the values of the thresholds and amplitudes of the motor response caused by transcranial and trans-spinal magnetic stimulations. A general pattern manifested in a significant decrease in thresholds and an increase in the amplitudes of motor responses caused by trans-spinal magnetic stimulation in both muscles gas been discovered. Specifically, the threshold of spinal evoked motor responses in both muscles decreased by 20%, and the amplitude increased by 150% after the end of immersion. The data obtained during the experiment confirm the spinal nature of the origin of hypogravitational hyperreflexia.

Weightlessness can affect the vestibular function, primarily the otolith function, both directly due to the loss of gravitational influence and by eliminating the support and minimizing proprioceptive afferentation, influencing indirectly through the central integrative multisensory structures of the central nervous system (CNS), where the convergence of afferent signals of various sensory modality (primarily visual, vestibular, support and motor) occurs. All this prompted the study of the influence of various afferentations on the otolith-ocular reflex under the conditions of real and simulated weightlessness. Using the video oculography method, 58 Russian cosmonauts, members of long-term missions to the ISS (125–219 days, ~175 days on average), were examined by a static torsional otolith-cervical-ocular reflex (OCOR) with a head tilt to the shoulder at an angle of 30 deg, the otolith-ocular reflex (OOR) when the body is tilted at an angle of 30 deg, and the otolith-ocular reflex when exposed to centrifugal acceleration using a centrifuge (OORCF). Nine out of 58 cosmonauts were examined in microgravity (175 days) as part of the Virtual space experiment (Stage 1). The study of simulation of the spaceflight (SF) factors involved 30 subjects during five- or seven-day horizontal “dry” immersion (DI) and 12 subjects in 60-day head-down tilt (–8 deg) bed rest (BR). The procedure and the corresponding hardware and software used both in studies with the participation of cosmonauts and in model experiments were completely identical. In weightlessness, throughout the whole SF, all the cosmonauts surveyed had a significant OCOR decrease with the presence (from 11 to 55%, depending on the flight day) of the atypical (inversion or absence) otolith-ocular reflex. After SF, on days 1–4 of examination, 80% of the cosmonauts exhibited a significant OCOR/OOR decrease; 34% of the cosmonauts had atypical (inversion or absence of the otolith reflex) vestibular reactions, while no differences were found between OCOR and OOR. Statistically significant differences were found between the values ​of the OCOR/OOR and OORCF reflexes before and on days 4–5, 9–12 after SF. On days 2–3 after SF, no difference between OORCF and OCOR/OOR was observed. The return of the otolith reflex to the baseline took place only on day 9 after SF. The OCOR/OOR study on days 1–3 after DI showed that the otolith-ocular reflex in 47% of those examined was significantly reduced; in 13% of the subjects atypical reactions (absence or inversion of the reflex) were recorded. On days 4–6 after DI, OCOR/OOR returned to the baseline in all subjects. Analysis of OCOR/OOR after the BR experiment showed that only 14% of the surveyed had a significant decrease in OCOR/OOR on day 1 after the experiment. The atypical form of OCOR/OOR (inversion or complete absence of the otolith reflex) after BR was not revealed in contrast to the testers after DI. The results obtained demonstrated the influence of nonvestibular afferentation on the intensity of the otolith-ocular reflex and its dependence on other sensory inputs.

The study of eye hydrodynamics following five-day “dry” immersion (DI) was aimed at evaluating the influence of compensatory body hypohydration on the intraocular hydrodynamic balance. For the first time the data of electronic eye tonography before and after modeled microgravity were compared. The study involved ten male volunteers 24 to 40 years of age without ophthalmologic pathologies. Electronic eye tonography results and hypohydration dynamics were assessed by fluid balance. Electronic tonography was performed before DI and on post-DI days 1 and 7 to measure the true intraocular pressure and to calculate the intraocular fluid production rate (F), coefficient of aqueous humor outflow ease, Bekker coefficient, and trophic coefficient (TC). On post-DI day 1, F reduction was observed in eight volunteers (60% of cases, 12 eyes). Level of the F reduction varied from 40% of the baseline value (5 eyes) to abnormally low 54% (7 eyes) underlying trophic changes. TC went down in 60% of cases (12 eyes); in 50% of cases (6 eyes) TC reduction was clinically significant. By the seventh day after DI, intraocular hydrodynamics was comparable with the baseline. It is hypothesized that the reflectory hypohydration during DI (the Gauer–Henry reflex) is responsible for changes in the intraocular hydrodynamics; the depth of these changes is determined by the degree of compensatory hypothalamic influence upon the antidiuretic hormone-angiotensin II system.

Electromyostimulation plays an important role along with other means of rehabilitation and training in sports, clinical and space medicine. Many laboratories in the world are involved in the development of new modes and hardware for electrical stimulation of skeletal muscles and in the study of the physiological effects of electromyostimulation. In the clinical setting, chronic low-frequency, low-intensity stimulation is usually applied with a view to preparing muscle tissue for cardiomyoplastic surgery, correcting the state of a paralyzed muscle, and to rehabilitating patients with the hypokinetic syndrome. This review is devoted to the study of the physiological basis (mechanisms of action) of chronic low-frequency stimulation. In the early 1970s, a model of chronic low-frequency electrical stimulation of the muscles of laboratory animals was developed and widely studied. As a result of numerous studies it was established that such stimulation led to an increase in muscle performance, fatigue resistance, the activities of oxidative enzymes and other structural and metabolic markers, as well as to a sustained fast-to-slow muscle fiber transformation. Similar data were obtained in the studies of healthy volunteers. Low-frequency stimulation had a beneficial effect on the atrophied disused muscle. The review examines the advantages and disadvantages of low-frequency electromyostimulation in relation to deconditioned muscle rehabilitation.

This review is dedicated to the memory of Inesa Kozlovskaya, whose contributions to gravitational physiology was and will continue to be decisive. Dr. Kozlovskaya has developed the concept of gravity-dependent motor control and substantiated the role of supporting afferentation in postural – tonic regulation. It was shown that the support afferentation plays the leading role in the control of the tonic muscle system and regulation of postural synergies. In this review the modern mechanisms of posture-locomotion integration as well as the mechanisms of sensory-motor regulation based on stimulation of foot and muscle receptors in combination with spinal cord stimulation will be considered. Based on the results presented in this review the concept of neurorehabilitation is proposed to be considered as the implementation of various neuromodulations aimed at regulating the functional state of the injured nervous system. The concept is based on the interaction of the processes of regulation of the functional state of the injured brain and sensory input during executing of motor tasks.

A review of the currently available ideas about the role of gravitational factor in the activity of the sensorimotor and cardiovascular systems, as well as new fundamental problems and questions for space medicine and physiology, is presented. The review presents data on the embryogenesis of animals under conditions of weightlessness, the evolution of the motor and cardiovascular systems and the peculiarities of their functioning under conditions of gravity, as well as in the change of gravitational load. Much attention is paid to the results of unique studies in modeling gravitational unloading on Earth: antiorthostatic hypokinesia, dry immersion and suspension, which made it possible to study the mechanisms of regulation of various body systems under conditions of altered gravity. Terrestrial organisms have learned to function in the gravitational field. Almost all systems of their body are gravitationally dependent. However, the extent and mechanisms of this dependence have long remained unclear. Space flights have opened up the possibility of studying the activity of living systems in the absence of gravity. Among the factors mediating the effect of weightlessness on the motor system, changes in the activity of sensory systems occupy an important place. Under the Earth conditions, the afferent support of motion control systems is polyreceptive: this is vision, and the vestibular apparatus, supporting and muscular afferentations. In zero gravity, the activity of some channels is completely eliminated (support afferentation), others are distorted (vestibular apparatus), and still others are weakened (proprioception). Similar processes occur in the cardiovascular system: with the loss of the pressure gradient caused by gravity, profound changes occur in the structure and functioning of the heart and vessels, both resistive and capacitive. The question of how much the various changes occurring in the cardiovascular system are associated with the disappearance of the gravitationally dependent pressure gradient is still open. It is not possible to solve all the problems of gravitational physiology In space flights. Therefore, various methods have been developed for simulating gravitational unloading on Earth. New data on the mechanisms of changes occurring in the sensorimotor system were obtained by comparing flight data and data obtained in model experiments. The fundamental problem for the gravitational physiology of cardiovascular system is the degree of correspondence of the changes observed in laboratory animals and under model conditions (antiorthostatic hypokinesia, immersion, suspension) with the changes that are recorded in real space flight in humans. This problem is specially discussed in the review. At the same time, in the light of the upcoming interplanetary expeditions, many questions remain unresolved, in particular, the problems of post-flight readaptation of the motor and cardiovascular systems to gravity conditions. This is a fight against loss of strength, endurance, orthostatic instability. The development and improvement of a system for preventing the negative effects of space flight factors is impossible without understanding the mechanisms of development of the observed changes.

The paper discusses the findings of studying neuroplastic transformations in the brain cortex owing to stroke patients therapy using soft multimodel exoskeleton complex (MEC) REGENT in comparison with activation of the cortex structures controlling locomotion in healthy people. The MEC course applied to hemiparetic patients increases walk speed; changes in the activity zones detected by functional magnetic resonance imaging (fMRI) attest to the positive trajectory of neuroplastic processes, i.e. activation in the precentral gyrus (primary motor cortex), secondary association cortex (inferior parietal lobule) on the damaged hemisphere, and right-side primary sensorimotor cortex. Analysis of the functional connectivity between the areas of interest before and after the MEC therapy elicited significant changes in the inter- and intra-hemispheric connections. This positive cortical reorganization has its origin in reduction of excitory interactions between the secondary associative areas (inferior parietal lobules in both hemispheres) and alleviation of the inhibitory interaction between the inferior parietal lobule and primary right-side sensorimotor cortex in the damaged hemisphere.

The review is an attempt to describe and give a meaning to the accumulated data about the mechanisms controlling the structure and functionality of the postural muscle the almost continuous work of which makes it possible for the humans and animals to exist actively on Earth's surface. A great bulk of these data was obtained, described and systematized by professor I.B. Kozlovskaya and her pupils. A body of the most interesting facts and regularities was documented in other laboratories and research centers, quite often under the influence of ideas suggested by I.B. Kozlovskaya. The concept of the tonic system, that is, an integral physiological apparatus comprising not only slow and fast muscular fibers and small controlling motoneurons but also a complex of the brain (up to and including the striatum and motor cortex) and sensory mechanisms, constitutes the most important parts of her theoretical legacy. The fundamental conclusion of this review is that the gravity-dependent tonic contracting activity of the postural muscle controlled by the nervous system and afferent mechanisms is key to maintaining its structure, signal pathways and mechanic properties crucial for its constant anti-gravity activity.

A joint NASA and Institute of Biomedical Problems (IBMP) study, designated as the Field Test, was designed to investigate how the immediate post-flight effects of long duration spaceflight impact performance on vestibular and sensorimotor-related functional tasks. One unique feature of this study was the use of functional tests typically associated with everyday living to track recovery. These tasks are also expected of crewmembers during recovery operations and include sit-to-stand and prone-to-stand transitions, translating objects, and jumping down from a platform. This paper provides an overview of the methodology used for the Field Test. As an example of the functional deficits observed, we present results for a seat egress and walking task that involved turning 180 degrees and stepping over obstacles. We observed significant increases in the time-to-complete this task on landing day. We recommend this task being incorporated into Standard Measures to evaluate the efficacy of countermeasures. The decrements observed at landing day have implications for the deconditioned crew during exploration missions where crewmembers will be unassisted after landing on a planetary surface.

It is believed that real movements and those performed mentally (imaginary movements) are functionally similar. This hypothesis is based on the use of the imaginary movement approach for the investigation of the neurophysiological mechanisms of real movements of a person, as well as for rehabilitation and optimization of motor functions. A large body of evidence in favor of this hypothesis has been obtained for upper limb movements, whereas data on lower limb movements are quite scarce. The aim of this review is to generalize the published data that demonstrate the similarity of the mechanisms and brain structures involved in the organization of imaginary and real locomotion.

Inesa Benediktovna Kozlovskaya is the head of a branch of the Institute of Biomedical Problems of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, Honored Scientist and Engineer of the Russian Federation, a specialist in gravitational physiology, a participant in biomedical investigations during the spaceflights of the orbital stations Salyut-7, Mir, and ISS, as well as the flights of Bion biosatellites. She is one of the developers of the system of counter measures against unfavorable changes in the body in manned flights. She founded the school of the gravitational physiology of movements. Her scientific achievements are awarded with Russian and international prizes and awards. The editorial board of the journal sincerely congratulates Prof. Kozlovskaya on her ninetieth birthday and wishes her well-doing and many more years of active life.

This review addresses the use of robotic devices in the rehabilitation of poststroke and posttrauma patients as a rehabilitation technology which has developed rapidly over the last decade. The types of devices used are described – manipulators and exoskeletons – along with the clinical protocols for their use and the effectiveness of rehabilitation procedures. Particular attention is paid to the neurophysiological basis of the rehabilitation potential of this technology, including analysis of measures of plastic rearrangements of the brain. Results obtained from state-of-the-art rehabilitation technology using hand exoskeletons controlled by brain–computer interfaces based on kinesthetic motor imagery are considered.

Neuromuscular electrical stimulation (NMES) of large muscle groups in patients with stable chronic heart failure (CHF) increases physical work capacity and muscle strength. The safety and efficacy of short courses of NMES in patients with decompensated CHF has not been studied. The aim of the study was to compare the impact of leg NMES, interval bicycle training, and conventional treatment on the functional capacity and quality of life in patients hospitalized with decompensation of CHF. A total of 51 patients (84.3% of men; mean age, 62.5 ± 3.3 years) hospitalized with decompensated CHF were divided into three groups: optimal pharmacological therapy (OPT) + three weeks of NMES of thigh and shin muscles starting within the first three days after admission (n = 10), OPT + three weeks of bicycle exercise training (BET) starting on the fifth to seventh day (n = 20), and the control group of OPT only (n = 21). At baseline and after the three-week symptom-limited cardiopulmonary exercise test, 6-min walk test, Duke Activity Status Index (DASI) and quality of life assessment by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) were performed. Patients in the NMES and BET groups presented with similar increases in the 6-min walk distance, plus 65.0 (50.0; 112.5) and 53.0 (51.0; 78; 0) m; DASI, plus 8.6 (5.5; 11.8) and 8.0 (4.5; 9.0) points; and VO2peak, plus 1.9 (0.3; 3.2) and 2.2 (0.7; 3.2) mL/(min kg), respectively. In the control group, only the 6-min walk distance increased significantly (+21 m). The improvement in the MLHFQ score was observed in all the three groups: maximal in the BET group and minimal in the NMES group. Three weeks of leg muscle electrical stimulation and bicycle training provide similar improvement in physical capacity, daily activity, and the quality of life in patients hospitalized for severe CHF. The efficacy of NMES is comparable with low to moderate intensity interval bicycle training and well tolerated by patients.

We analyzed the signaling processes initiating proteolytic events in the human soleus muscle during short-term exposure under the non-weight-bearing conditions. Dry immersion (DI) was used to induce weight deprivation in the m. soleus for 3 days. Western blotting was used to determine the level of insulin receptor substrate 1 (IRS-1), total and phosphorylated neuronal NO synthase (nNOS), and adenosine monophosphate-activated protein kinase (AMPK), which control the anabolic and catabolic signaling pathways, and the level of cytoskeletal protein desmin and Са2+-activated protease calpain. By day 3 of DI, calpain- dependent proteolysis manifests itself by reductions in both the total content and level of nNOS phosphorilation. The rate of AMPK phosphorylation was significantly decreased.

This review discusses the functioning of the motor system under normal and reduced gravity. Analysis of the experimental data led to the conclusion that all changes in the functioning of tonic muscular system are related to each other. When transiting to the state of microgravity, changes are caused by one common factor, namely a sharp decrease in the activity of support afferent input, specifically oriented to the perception and analysis of gravitational loads and firmly embedded in the mechanisms of postural synergism organization. We analyzed data obtained in studies on the activation of cortical areas of the brain during the stimulation of support afferents in order to test the hypothesis that such stimulation in both healthy subjects and patients with neurologic deficiency leads to activation of both the sensory and motor cortex involved in supraspinal control of the movement of the lower limbs, in particular when walking.

The present experiments were designed to gain additionally insight into how the spinal networks process direct spinal stimulation and peripheral sensory inputs to control posture and locomotor movements. We have developed a plantar pressure stimulation system that can deliver naturalistic postural and gait-related patterns of pressure to the soles of the feet to simulate standing and walking, thereby activating and/or modulating the automated spinal circuitry responsible for standing and locomotion. In the present study we compare the patterns of activation among selected motor pools and the kinematic consequences of these activation patterns in response to patterned heel-to-toe mechanical stimulation of the soles of the feet, and/or transcutaneous electrical spinal stimulation, for postural and locomotion regulation. The studies were performed in healthy individuals (n = 12) as well as in subjects (n = 2) with motor complete spinal cord injury. We found that plantar pressure stimulation and/or spinal stimulation can effectively facilitate locomotor output in the subjects placed with their legs in gravity neutral position. We have shown synergistic effects of combining sensory and spinal cord stimulation, suggesting that the two networks are different, but complementary. Also we provide evidence that plantar stimulation could serve as a novel neuro-rehabilitation tool alone or as part of a multi-modal approach to restoring motor function after complete paralysis due to SCI.

Nowadays it is widely believed that the animal motor system historically evolved under the powerful pressure of gravity forces. By the late 1970s, many manifestations of the microgravity effects on the motor system had already been known. At the same time, the basic sensorimotor relationships during exposure to zero-gravity remained unexplored. The article considers the main results of the studies of the scientific school of I.B. Kozlovskaya regarding the roles of the gravitational forces in the functioning of the tonic motor system in humans and other mammals. In these studies, it was demonstrated that the muscle tonic system is relatively independent and possesses its own structures and mechanisms at every level—from receptors to effectors. The support afferent input plays the main role in the regulation of the postural tonic system. The withdrawal of the support afferentation leads to the decline of the tonic motor units activity in extensor muscles and the alteration of the motor units recruitment patterns in the spinal cord. The decline of the tonic activity of the extensor motoneurons triggers on the development of the sensorimotor effects of microgravity including atony and muscle atrophy.

According to the results of the experiment performed on board the International Space Station with participation of 15 Russian cosmonauts, comparative analysis of efficacy of two models of preventive measures used by the Russian members of long-term space missions is carried out: intense interval training in the aerobic–anaerobic power zone (recommended model) and continuous low-intensity exercises in the aerobic power zone of muscle activity energy supply. Interval training in space flight provided the maintenance of the level of physical performance close to the pre-flight level as indicated by the maximum running speed, physiological value of work, and the lactate level after performing the standard load. We describe putative mechanisms of counteraction to adaptive rearrangement of the propulsion system in zero gravity and expand understanding of the laws governing human body’s interaction with Earth’s gravitational field. The research results presented in this paper show the high preventive efficacy of interval training compared with regular aerobic training, which is very important now in the time of searching for means and methods of prevention of hypogravitational alterations during interplanetary missions.

The effects of additional dynamic visual stimuli (retinal optokinetic stimulation (ROKS)) on the visual–manual tracking (VMT) indicators in the absence of support afferentation and with a reduced level of proprioceptive afferentation were determined using a model of horizontal “dry” immersion. The accuracy of the VMT of jerky and smooth (linear, pendular, and circular) movements represented by visual dot stimuli was evaluated in all 18 participants aged 19–31 before, during and after their exposure to a five- to seven-day immersion bath. The eye movements were recorded by electrooculography, while the hand movements were recorded by a joystick with a biological visual feedback (the current angle of the joystick handle was imaged on the screen). Computerized visual stimulation tests were presented, through virtual reality glasses, to subjects in the absence and against the background ROKS. We analyzed the temporal and the amplitude- and velocity-related visual and manual tracking (VT and MT) characteristics, including the efficiency (e) and gain (g) coefficients as the ratios between the amplitudes and velocities of eye/hand movements and the amplitude of stimulus movements. The efficiency and gain coefficients of both VT and MT without ROKS were significantly decreased against the baseline during the entire period including three days of immersion and 3 post-immersion days. The most pronounced worsening was observed in the VT parameters. Whereas the VT and MT parameters remained unchanged against the threshold ROKS before the immersion, they were improved during and after the immersion (the improvement was significant on the fifth to seventh day of immersion and on the thirdthird post-immersion day, compared to the test indicators on the clean screen). The most pronounced impact of ROKS was observed in the VT parameters. The vestibular function (VF) was evaluated by videooculography before and after immersion. We analyzed the static torsional otolith-cervicalocular reflex (OCOR), dynamic vestibular-cervical-ocular reactions (VCOR), vestibular reactivity (VR), and spontaneous eye movements (SpEM). A significant decrease in OCOR (gOCOR was 0.1, compared to the background gOCOR value of 0.25) was detected alongside a simultaneous significant increase in the VCOR/VR parameters in 28% of subjects on day R + 1 after immersion. Correlational has been found between the parameters of VT and MT, as well as between those of VF and VT, but no correlation has been found between the VF and MT characteristics. The results have shown that the removal of support afferentation and the minimization of proprioceptive afferentation more affected the accuracy of VT rather than that of MT. The correlational links between the studied parameters against the background of ROKS were not only preserved, but also intensified. The obtained results confirm the development of sensory deprivation (and afferent deficit) under the exposure to an immersion bath and indicate the approach to correcting the sensory deprivation through additional ROKS.

The mechanisms underlying the locomotion recovery in poststroke patients remain unknown. Navigated transcranial magnetic stimulation (nTMS) is a new method to evaluate the functional state of the motor system. Using of the “Regent” soft exoskeleton complex (SEC) allow to correct walking pattern significantly. The aim of this study was to evaluate the capability of nTMS to assess changes in gait cortical control using SEC in poststroke patients. 14 patients of the subcortical stroke (the mean age was 53.0 years, the mean time from stroke onset was 14.2 months) received 10 training sessions with SEC. The patients received nTMS before and after the sessions, as well as they were clinically evaluated by the Fugl–Meyer scale section for lower extremity and a 10-m walk test. Whereas a reliable reduction in the time of walking for 10 m was recorded after the sessions with the application of SEC, the Fugl-Meyer scale assessment remained unchanged. During nTMS, a reduction was recorded in the average latency of evoked motor response from the affected hemisphere, as well as various patterns of changes in the size and localization of cortical representations of the leg muscles. We have concluded that the nTMS method allowed us to identify the individual patterns of changes in the cortical representations of leg muscles as a result of the use of SEC in post-stroke patients with injuries in a group of locomotor system elements, thus identifying not only the fact of the undergoing neuroplastic processes, but also their direction.

The effect of a treatment course with a Regent multimodal complex exoskeleton (MCE) on the reorganization of cortical locomotor zones was studied in 14 patients with post-stroke hemiparesis, mainly in the chronic stage of the disease. Specific activation zones were identified prior to treatment in the primary sensorimotor and supplementary motor areas and the inferior parietal lobules of both affected and healthy hemispheres by functional magnetic resonance imaging (fMRI) used in a special passive sensorimotor paradigm. After a treatment course with the MCE, temporal characteristics of walking were found to improve, which was accompanied by a decrease in the activation zones of the inferior parietal lobules, especially in the healthy hemisphere, and a significant increase in the activation zones of the primary sensorimotor and supplementary motor areas. Significant changes in intrahemispheric and interhemispheric interactions were revealed by analyzing the functional connectivity of the zones under study before and after a course of treatment with the MCE.

The study discusses Russia’s system of preventive countermeasures and its general principles based on a successful experience accumulated by many crews of long-duration missions on Russian space stations. The preventive system tested during the exploitation of the International Space Station (ISS) was described in detail. For example, differences in training workouts performed by cosmonauts allowed specialists to distinguish two exploitation phases on the ISS. The recorded locomotion workouts performed by cosmonauts displayed departures from the onboard documentation. The concluding section of the paper discusses prospects for developing a system of preventive countermeasures for interplanetary missions.

BACKGROUND The purpose of this work was to investigate the brain's rhythmic activity during a simulated microgravity condition (namely dry immersion). METHODS During dry immersion, which lasted for 5 d, nine subjects (healthy men, 20 to 29 yr of age) were individually placed in a tub (2.2 × 1.1 × 0.85 m) filled with water (temperature was kept constant at about 33°C). Subject floated in the tub without bodily support in the supine horizontal position, but isolated from the water by waterproof material. Resting state EEGs were registered at the fourth or fifth day of dry immersion. Under the control conditions, resting state EEGs were registered while subjects laid in a supine position on a couch. RESULTS Compared to the control condition, EEG power in the alpha range (8-13 Hz) was greater in dry immersion; this effect was distributed across the whole scalp. No effects of dry immersion were found for the beta, delta, or theta frequency bands. CONCLUSION The results of the study, similar to those obtained in a real spaceflight, indicate that support withdrawal is an important contributor to brain activity alterations in weightlessness.Lazarev IE, Tomilovskaya ES, Kozlovskaya IB. Resting state brain activity during long-term dry immersion. Aerosp Med Hum Perform. 2018; 89(7):642-647.

The effects of mechanical stimulation of the sole support zones on the state of the m. soleus moto-neuron pool in humans have been studied under 7-day support unloading conditions, which were simulated using a dry immersion (DI) model. The excitability of the m. soleus motoneuron pool was estimated by the H-reflex amplitude normalized by the maximal M-wave amplitude before, during, and after immersion exposure. The results were compared for two groups of volunteers, i.e. a control group, which was subjected only to immersion exposure, and a test group, in which mechanical stimulation in locomotion regimens was applied daily during DI. The relative H-reflex amplitude increased during immersion in the control group, whereas such alterations were not detected in the test group.

The experiments reported here showed that decerebrate cats can actively maintain posture during standing and walking. On standing, postural corrections consisted of redistribution of extensor muscle activity in response to perturbations. Correcting reactions during walking included changes in the durations of the swing and transfer phases of the locomotor cycle, modulation of supporting force reactions, and modification of flexor and extensor function. Detailed analysis of correlations between muscle activity, supporting force reactions, and the kinematics of truncal and hindlimb movements showed that the motor system of the decerebrate animal can use a combination of feedback and feedforward to regulate dynamic balance during locomotion. Furthermore, balance was rapidly restored after impairment due to stumbling or perturbing influences. The intraspinal neural networks and somatosensory afferent input from the limbs can effectively regulate balance during walking and standing, without involvement of the vestibular and visual systems. After interruption of the connection with the motor centers of the stem and forebrain in decerebrate and spinal animals, these networks were in a suppressed state but could be activated by epidural and sensory stimulation substituting for tonic supraspinal drive.

The space medicine data on the nature of motor disorders suggest an important role of the support inputs in the control of mammalian tonic and postural systems. Progress in functional magnetic resonance tomography (fMRT) makes it possible to perform in vivo analysis of various brain areas during stimulation of the support afferentation. Under these conditions, specific activation of the brain cortical areas was studied in 19 healthy subjects (with the mean age of 38 ± 15.13 years) and 23 patients (with the mean age of 53 ± 9.07 years) with focal CNS lesions (cortical-subcortical ischemic stroke). During scanning of subjects, the support areas of the soles of the feet were stimulated using a block design to simulate slow walking. In healthy subjects, significant activation was recorded (p < 0.05 at the cluster level) in the primary somatosensory cortex, premotor and dorsolateral prefrontal cortex, and insular lobe. In patients that had had a stroke, activation of the locomotion-controlling supraspinal systems clearly depended on the stage of the disease. In patients with a cortical-subcortical stroke, the pattern of contralateral activation of the sensorimotor locomotion predominated during motility rehabilitation.

Methods that, on the one hand, can ensure patient’s mobility and, on the other hand, activate afferent inputs are the main in the rehabilitation treatment. Recent studies have shown that plasticity is the structural basis of recovery after central nervous system lesions. Reorganization of cortical areas, increase in the efficiency of the functioning of preserved structures; and active use of alternative ascending pathways, e.g., intensification of afferent input, constitute the anatomical basis of plasticity. However, sensory correction methods, without accounting of functional condition of patients, may lead to the formation of pathological symptoms: spasticity, hyperreflexia, etc. So, the main aim is to study adequate management of the neuroplasticity process. This problem cannot be solved without modern methods of neuroimaging and brain mapping. The new approach for the study of cortical mechanisms of neuroplasticity, responsible for locomotion, was developed in the present study. This approach is an integrated use of functional magnetic resonance imaging (fMRI) and navigation transcranial magnetic stimulation (nTMS). It has been shown that vast fMRI activation area in the first and second sensorimotor areas emerges with a passive sensorimotor paradigm usage that imitates backing load during walking. The Korvit mechanical stimulator of backing zones of footsteps is used to create this paradigm. The nTMS examination used after fMRI helps to localize motor representation of muscles which control locomotion more accurately. We assume that the new approach can be used for studying the neuroplasticity process and assessing neuroplasticity changes when taking rehabilitation measures to restore and correct the walking process.

The aim of the study was to examine effects of long-duration exposure to weightlessness on characteristics of the vertical gaze fixation reaction (GFR). The subjects were to perform the target acquisition task on visual stimuli that appeared at a distance of 16 deg. up- and down from the primary position in a random order. Experiments were performed before launch, during flight and after landing. Before flight time of gaze fixation reaction did not exceed 650 ms. During space flight (SF) it extended up to 900–1000 ms and more. The velocities of head movement in space decreased, but the velocities of eye counterrotation decreased to a lesser degree. This difference resulted in sharp increase of vertical vestibular ocular reflex (VOR) gain (up to 4.3 values in one of the cosmonauts) during the 1st month of flight; further it decreased reaching the values of 0.5–0.7 on the 5th month of SF. After landing vertical VOR gain increased greatly again. These results in the vertical axis are in agreement with the data of Kozlovskaya et al., which showed in experiments with monkeys that horizontal VOR gain increased together with redundant inadequate responses of vestibular nucleus on vestibular stimulation and that in the course of adaptation to these conditions central nervous system inhibited vestibular input from the motor control system.

Biomechanical and electromyographic characteristics of locomotion were studied before and after a space flight on days 3, 7, and 10 after landing in 18 participants of prolonged space missions on board the International Space Station. It has been shown that microgravity causes significant changes in biomechanical and electromyographic characteristics of walking, such as a decrease in the amplitude of angular displacement in leg joints, a decrease in the double step length, and an increase in the electromyographic costs of locomotion. It has been also shown that interval locomotor physical training, such as alternation of running and walking, in prolonged space flights prevents an increase in the physiological costs of locomototions after a space flight and provides more efficient maintenance of the neuromuscular system’s performance after a flight. Cosmonauts who performed interval locomotor training had fewer changes in biomechanical and electromyographic characteristics of walking.

Dry immersion is an effective and useful model for research in physiology and physiopathology. The focus of this study was to provide integrative insight into renal, endocrine, circulatory, autonomic and metabolic effects of dry immersion. We assessed if the principal changes were restored within 24 h of recovery, and determined which changes were mainly associated with immersion-induced orthostatic intolerance. Five-day dry immersion without countermeasures, and with ad libitum water intake, standardized diet and a permitted short daily rise was performed in a relatively large sample for this experiment type (14 healthy young men). Reduction of total body water derived mostly from extracellular compartment, and stabilized rapidly at the new operating point. Decrease in plasma volume was estimated at 20% - 25%. Five-day immersion was sufficient to impair metabolism with a decrease in glucose tolerance and hypercholesterolemia, but was not associated with pronounced autonomic changes. Five-day immersion induced marked cardiovascular impairment. Immediately after immersion, over half of the subjects were unable to accomplish the 20-min 70° tilt; during tilt, heart rate and total peripheral resistance were increased, and stroke volume was decreased. However, 24 hours of normal physical activity appeared sufficient to reverse orthostatic tolerance and all signs of cardiovascular impairment, and to restitute plasma volume and extracellular fluid volume. Similarly, metabolic impairment was restored. In our study, the major factor responsible for orthostatic intolerance appeared to be hypovolemia. The absence of pronounced autonomic dysfunction might be explained by relatively short duration of dry immersion and daily short-time orthostatic stimulation.

The lateral stiffness and electromyogram characteristics of the resting calf flexor and extensor muscles have been studied in 18 subjects during a seven-day immersion with and without mechanical stimulation of the foot support zones. It has been shown that as early as day 1 of support deprivation, the lateral stiffness steadily decreases in the m. soleus and, in contrast, drastically increases in the m. tibialis anterior. A mechanical stimulation of the foot support zones decreases the rate and degree of the changes observed in both muscles. The tight correlation of the changes in the lateral stiffness with the muscle activity suggests a significant dependence of these changes on the electromyogram characteristics at rest.

A new method for the activation of spinal locomotor networks (SLN) in humans by transcutaneous electrical spinal cord stimulation (tESCS) has been described. The tESCS applied in the region of the T11-T12 vertebrae with a frequency of 5–40 Hz elicited involuntary step-like movements in healthy subjects with their legs suspended in a gravity-neutral position. The amplitude of evoked step-like movements increased with increasing tESCS frequency. The frequency of evoked step-like movements did not depend on the frequency of tESCS. It was shown that the hip, knee, and ankle joints were involved in the evoked movements. It has been suggested that tESCS activates the SPG (SLN) through in part, via the dorsal roots that enter the spinal cord. tESCS can be used as a noninvasive method in rehabilitation of spinal pathology.

Numerous studies on the mechanisms of the motor control carried out in the interests of space medicine resulted in a concept on the leading role of the support afferent input in the regulation of the postural tonic system in mammals. The implementation of functional magnetic resonance imaging (fMRI) has permitted in vivo brain mapping during stimulation of the support afferent input. The goal of this study was to identify activated regions in the brain during mechanical stimulation of the plantar support zones in different modes using a special Korvit simulator. Twelve healthy volunteers (six women and six men) aged from 22 to 42 years were studied using fMRI, each of them was scanned once. The fMRI protocol for each subject consisted of two different blocked paradigms: (1) with the soles of a subject stimulated in an imitated standing mode and (2) with the soles stimulated in an imitation slow-walking mode. The patterns of activation in each mode were analyzed using the SPM5 statistical software package for each subject and for the group as a whole. All the paradigms showed significant activation (pcorrect < 0. 05 at the cluster level) in the primary somatosensory, premotor, dorsolateral and prefrontal cortices, as well as in the insula. The involvement of the prefrontal cortex during simulation of standing and a broad involvement of the primary and secondary sensorimotor cortices during simulation of slow walking were found.

Balance function is dramatically deteriorated after exposure to microgravity. The purpose of the present study was to investigate the role and the contribution of different gravity sensory systems to the development of balance impairment after long-term spaceflights. Postural perturbations (pushes to the chest) of the threshold, medium, and sub-maximal intensities were produced in eight cosmonauts before, and on the day 3, 7, and 11 following spaceflight. Postural corrective responses were analyzed by anterior-posterior body sway fluctuation and electromyographic activity of leg muscles. The characteristics of the postural corrective responses changed significantly on the day 3 following spaceflight: the amplitude of posterior sway caused by perturbation of threshold intensity was increased reaching 135% of preflight value; the corrective responses lasted more than 6 s in 50% of all trials, while it did not last more than 4 s in 96% before spaceflight. The EMG responses were characterized by increased contribution of medium- and long-latency reactions. On the day 11 following spaceflight, most of the characteristics of postural corrective responses were close to preflight values. We assumed that the balance alterations after spaceflight are caused by changes in weightlessness of functions of two main gravity sensory systems, namely, weight-bearing and vestibular one. The deficit of weight-bearing afferentation triggers a decline of the extensors’ muscle tone, while changes of vestibular function cause a decline of accuracy of postural corrections.

Immersion is a useful tool for studying fluid-volume homeostasis. Natriuretic peptides play a vital role in renal, humoral, and cardiovascular regulation under changing environmental conditions. We hypothesized that dry immersion would rapidly induce a new steady state for water and sodium metabolism, and that serum NT-proBNP levels, a proxy measure for brain natriuretic peptide (BNP), would decrease during long-term dry immersion and increase during recovery. Eight healthy young men were studied before, during, and after 7 days of dry immersion. Body weight, water balance, and plasma volume changes were evaluated. Plasma and serum samples were analyzed for active renin, NT-proBNP, aldosterone, electrolytes, osmolality, total protein, and creatinine. Urine samples were analyzed to determine levels of electrolytes, osmolality, creatinine, and free cortisol. A stand test was performed before and after dry immersion to evaluate cardiovascular deconditioning. Long-term dry immersion induced acute changes in water and sodium homeostasis on day 1, followed by a new steady state. Plasma volume decreased significantly during dry immersion. The serum levels of NT-proBNP increased significantly in recovery (10 ± 3 ng/L before dry immersion vs. 26 ± 5 ng/L on the fourth recovery day). Heart rate in the standing position was significantly greater after immersion. Results suggest that chronic dry immersion rapidly induced a new level of water-electrolyte homeostasis. The increase in NT-proBNP levels during the recovery period may be related to greater cardiac work and might reflect the degree of cardiovascular deconditioning.

The results of extended comparative research in the effect of hypogravity on the motor system in space flights and ground-based experiments have shown that “dry” immersion (DI) is the most adequate model of microgravity—the time of development, and the volume and depth of structural and functional motor disorders in DI are very close to what is observed in real microgravity. The high intensity and speed of development of hypogravity effects during immersion hypokinesia in comparison with bed rest hypokinesia, differing from DI only by the level of support deafferentation, promoted an insight into the leading (triggering) role of support lessness in the genesis of microgravity-induced syndromes of muscular deconditioning and hypogravitational ataxia. The involvement and pathways of support afferentation within the muscular system were experimentally studied and verified. The mechanisms of the development of changes in the activity of the system mechanisms remain much less investigated. These issues, as well as some new approaches for the elimination of the negative effects of hypogravity, were the subjects of investigation in the program of a complex dry immersion experiment, the results of which are presented in this issue of the journal.

The article summarizes the results of the development of preventive measures (PMs) performed by the team headed by Academician O.G. Gazenko (winner of the State Prize), as well as some data obtained in the following years at the Institute of Biomedical Problems of the Russian Academy of Sciences, where these measures were further developed. The system of prevention of adverse changes in the body of cosmonauts, which was first developed in Russia, provided successful implementation of long-term space flights (SFs) on board series of orbital stations (OSs) Salyut and the station Mir, which lasted from 64 to 438 days. This system includes performing physical exercises on a treadmill and bicycle ergometer, axial loading along the longitudinal axis of the human body by means of a Penguin suit, application of negative pressure to the lower part of the body by means of a pneumatic-vacuum spacesuit Chibis, and some other means. This system proved to be highly efficient, preventing or considerably decreasing the negative effects of microgravity throughout and after prolonged space flights.

A seven-day dry immersion experiment provided the opportunity to study the effects of decreased proprioceptive tactile and support afferentations on the vestibular function and visual-manual tracking. Before and after immersion, six subjects participated in a video oculographic evaluation of the static torsion otolith-cervicoocular reflex (OCOR) in response to head tilt by 30° in the frontal plane and dynamic vestibular-cervicoocular reactions to head longitudinal rotations at 0.125 Hz. In addition, the hand-eye motor coordination of tracking a jerky (sinusoidal) or smooth (linear) movement of point targets along the horizontal or vertical lines was evaluated on the basis of the data of electrooculography and records of manipulations with the joystick during immersion. A computerized test was performed in virtual glasses displaying images of visual stimuli and hand motor acts. The computed parameters included the reaction’s latent time, amplitude, speed and time of eye and hand movements, and gains of optooculomotor reactions and manual tracking as a ratio of eye/hand to visual stimulus speed. Testing was carried out before the experiment, after 3 h of immersion, on days 3 and 6 of staying in the bath, in the initial hours after immersion and on the third day of recovery. It was shown that removal of support and minimization of proprioceptive afferentation had a profound effect on the ocular tracking rather than pursuing the visual stimulus by hand. The accuracy of manual tracking was better in comparison with the eye tracking in all subjects. This was the first observation of changes in the peripheral vestibular system in two out of six subjects, i.e., inversion of the static torsion OCOP and positional nystagmus against a background of converted reflex, which did not change the parameters of the visual-manual tracking.

Established with the personal participation of O.G. Gazenko, the Russian system of medical care for cosmonauts has been largely preserved to this day. The system was fully functional on board the orbital complex Mir and, with appropriate modifications, has been adopted as the core of the medical care for Russian members of ISS crews. In 2000–2008, 22 cosmonauts were members of 17 ISS missions lasting from 140 to 216 days. The main functions of the medical care system were to control health, physical, and mental performance, and to support space research. Readaptation to normal gravity was, in most cases, similar to what has been typical on the return from Russian orbital stations; some deviations are accounted for by the use of in-flight countermeasures. The paper presents some aspects of the theoretical work of Academician Gazenko in the field of medical care in space flights. It outlines the principles of ISS medical management. The integrated medical support system combines medical equipment and items available in the Russian and U.S. segments; the integrated medical group consists of flight surgeons, medical experts, and biomedical engineers of international partners and coordinates the planning and implementation of medical operations. In addition, challenges of health care in the phase of ISS operation are defined.

The results of the Russian-Austrian space experiment Monimir, which was a part of the international space program Austromir, are presented. The characteristics of the horizontal gaze fixation reaction (hGFR) to the visual targets were studied during long-term space flights. Seven crewmembers of the space station Mir participated in our experiment. The subjects were tested four times before the flight, five times during the flight, and three to four times after landing. During the flight and after accomplishing, the characteristics of gaze fixation reaction changed regularly: the reaction time and coefficient of the gain of vestibular-ocular reflex increased; the velocities of eye-head movements increased and decreased. These changes were indicative of a disturbed control of the vestibular-ocular reflex under microgravity conditions because of variability of the vestibular input activity. The cosmonauts that had flight and non-flight professional specializations differed in strategies of their adaptation to the microgravity conditions. In the former, exposure to microgravity was accompanied by gaze hypermetry and inhibition of head movements; conversely, in the latter, the velocity of head movements increased, whereas that of saccades decreased.

International audience; A sedentary lifestyle has adverse effects on the cardiovascular system, including impaired endothelial functions. Subjecting healthy men to 7 days of dry immersion (DI) presented a unique opportunity to analyze the specific effects of enhanced inactivity on the endothelium. We investigated endothelial properties before, during, and after 7 days of DI involving eight subjects. Microcirculatory functions were assessed with laser Doppler in the skin of the calf. We studied basal blood flow and endothelium-dependent and -independent vasodilation. We also measured plasma levels of microparticles, a sign of cellular dysfunction, and soluble endothelial factors, reflecting the endothelial state. Basal flow and endothelium-dependent vasodilation were reduced by DI (22 + or - 4 vs. 15 + or - 2 arbitrary units and 29 + or - 6% vs. 12 + or - 6%, respectively, P < 0.05), and this was accompanied by an increase in circulating endothelial microparticles (EMPs), which was significant on day 3 (42 + or - 8 vs. 65 + or - 10 EMPs/microl, P < 0.05), whereas microparticles from other cell origins remained unchanged. Plasma soluble VEGF decreased significantly during DI, whereas VEGF receptor 1 and soluble CD62E were unchanged, indicating that the increase in EMPs was associated with a change in antiapoptotic tone rather than endothelial activation. Our study showed that extreme physical inactivity in humans induced by 7 days of DI causes microvascular impairment with a disturbance of endothelial functions, associated with a selective increase in EMPs. Microcirculatory endothelial dysfunction might contribute to cardiovascular deconditioning as well as to hypodynamia-associated pathologies. In conclusion, the endothelium should be the focus of special care in situations of acute limitation of physical activity.

Physiological and methodological principles of the organization of physical training (PT) and its computerization during a space flight to Mars under the conditions of autonomous activity of the crew, including interaction with onboard medical systems, self-maintenance of health, preventive measures, diagnostic examinations, and, if necessary, treatment, are discussed. The conditions of unusually long-term autonomous space flights make the ground-based monitoring of the state of health of crew members substantially more difficult, which calls for computerization of the control over the crew members’ health, including prophylactic measures. The situation is further complicated because it is impossible to receive the necessary information from, and transmit it to, the spacecraft in a real-time mode or to quickly return the crew to Earth in case of an emergency. Under these conditions, physical prevention should be based on an onboard automated expert system ensuring the control over the activities of all crew members aimed at optimizing their psychophysical state. The problems of the control of training, including the use of an onboard automated expert system, are discussed.

Pre-and postflight examinations of cosmonauts participating in missions ISS-3 to ISS-9 on the International Space Station were performed using a computer-aided method of integrated assessment of the oculomotor system. The role and significance of the vestibular system in the eye tracking were determined; the individual and general characteristics of spontaneous oculomotor reactions and oculomotor reactions induced by visual and vestibular stimuli after a long-term stay at zero gravity (126–195 days) were determined; and the changes in the indices of oculomotor reactions were monitored. Studies of the vestibular function, intersensory interactions, and the tracking function of the eyes in the crew members were performed on the second, fifth (sixth), and ninth (tenth) days of the readaptation period. The results of the postflight examinations showed a significant change in the accuracy, velocity, and temporal characteristics of eye tracking and an increase in the vestibular reactivity. It was shown that the structure of visual tracking (the accuracy of fixational eye rotations and smooth tracking) was disturbed (the appearance of correcting saccades, the transition of smooth tracking to saccadic tracking) only in those cosmonauts who, in parallel to an increased reactivity of the vestibular input, also had central changes in the oculomotor system (spontaneous nystagmus, gaze nystagmus). With one exception, recovery of the indices of the accuracy of tracking eye movements in cosmonauts to the background level in the selected period of examination was not observed, although a positive trend was recorded.

The parameters of saccades and presaccadic slow potentials were studied in seven right-handed male volunteers with a dominant right eye before and after exposure to 6-day dry immersion. Visual stimuli were presented using three light diodes, which were located in the center of the visual field (the central fixation stimulus) and 10° to the right and left of it (peripheral stimuli (PSs)). The subjects performed a test with simple saccades to a PS and a test with antisaccades to the point located symmetrically in the opposite visual field. The EEG (19 monopolar leads) and electrooculogram were recorded. To isolate slow potentials, backward EEG averaging was performed, with the moment of switching on the PS serving as a trigger for the averaging. It was found that the characteristics of saccadic eye movements did not substantially change after exposure to immersion. However, both tests revealed a change in topography and a decrease in the amplitude of presaccadic slow negative potentials (PSNPs) during immersion. Characteristically, the focus of presaccadic negativity shifted to the right hemisphere so that the PSNP amplitude sharply decreased in the left and increased in the right hemisphere. A significant decrease in the PSNP amplitude on day 6 of immersion was found in the midline and left-hemispheric frontal and parietal leads. It may be suggested that, because of support unloading and a decrease in proprioceptive input, exposure to microgravity causes a decrease in the activity of the left hemisphere and prefrontal and parietal cortices, initially involved in preparation and realization of motor responses. The activation of the right hemisphere could be of compensatory character.

The parameters of saccades and presaccadic slow potentials were studied in right-handed men with a dominant right eye, including 19 schizophrenics and 12 healthy subjects. For visual stimulation, three light-emitting diodes were used, which were located in the center of the visual field (the central fixation stimulus) and 10° to the right and left of it (peripheral stimuli). Two stimulation protocols were used: with a simultaneous switching off of the central fixation stimulus and switching on of the peripheral stimuli (test 1) and with an interstimulus gap of 200 ms (test 2). According to the latency, saccades were divided into anticipatory, express, and regular. Slow EEG potentials preceding regular saccades were analyzed. It was found that the proportion of anticipatory saccades is considerably higher than the normal value in schizophrenia. The analysis of the presaccadic potentials demonstrated a significant decrease in the amplitude of negative potentials in the vertex region at early stages of presaccadic preparation and its increase in the occipital region at late stages. Test 2 in the patients demonstrated an increase in the positivity focus in the frontal region of the right hemisphere. It was assumed that the alterations found in schizophrenia result from the deficit of frontal cortical fields.