Velocity storage: its multiple roles.

Our research described in this article was motivated by the puzzling finding of the Skylab M131 experiments: head movements made while rotating that are nauseogenic and disorienting on Earth are innocuous in a weightless, 0-g environment. We describe a series of parabolic flight experiments that directly addressed this puzzle and discovered the gravity-dependent responses to semicircular canal stimulation, consistent with the principles of velocity storage. We describe a line of research that started in a different direction, investigating dynamic balancing, but ended up pointing to the gravity dependence of angular velocity-to-position integration of semicircular canal signals. Together, these lines of research and the theoretical framework of velocity storage provide an answer to at least part of the M131 puzzle. We also describe recently discovered neural circuits by which active, dynamic vestibular, multisensory, and motor signals are interpreted as either appropriate for action and orientation or as conflicts evoking motion sickness and disorientation.

Space motion sickness: A common neurovestibular dysfunction in microgravity.

This article presents a review of the current findings related to neurovestibular physiology, aetiology, and proposed theories on space motion sickness (SMS) during acute and sustained exposure to microgravity. The review discusses the available treatment options including medication and nonpharmacological countermeasure methods that help to prevent the development of SMS in weightlessness. Ground-based simulations using virtual reality, flight simulations, and Barany's chairs can be applied to study SMS and demonstrate its signs and symptoms to space crew members. Space motion sickness has been observed in approximately 70% of astronauts within the first 72 h in microgravity, having in general an instantaneous onset of signs and symptoms. Stomach discomfort, nausea, vomiting, pallor, cold sweating, salivation, tachypnoea, belching, fatigue, drowsiness, and stress hormone release have been documented. This can have detrimental effects on the well-being of astronauts in the initial phase of a space mission. Mental and physical performance may be affected, jeopardizing operational procedures and mission safety.

A Case Study of Severe Space Motion Sickness.

BACKGROUND: Motion sickness remains a significant and unpredictable problem during spaceflight. One of the major difficulties in understanding the etiology of space motion sickness has been a lack of data at the time the symptoms occur, i.e., immediately after entry into space and during return to Earth; in these phases of the mission is when critical operational tasks are performed. CASE REPORT: We report here the case of a crewmember who experienced severe motion sickness symptoms immediately after launching into space and for several days into the mission. Verbal reports recorded during and immediately after the flight describe in detail the symptoms and their underlying causes. The prominent cause was oscillopsia that was induced by moving the head, wearing prescription eyeglasses, and translating the whole body. DISCUSSION: In this case, space motion sickness was sudden and induced by voluntary or involuntary head or body movements in any plane. These head movements caused a visual disturbance that induced the perception that the environment was oscillating. The exaggerated motion perceptions suggest an increased vestibular sensitivity and/or decreased pursuit-optokinetic mechanisms in orbit and immediately after landing.Reschke MF, Wood SJ, Clément GR. A case study of severe space motion sickness. Aerosp Med Hum Perform. 2018; 89(8):749-753.

Intravestibular Balance and Motion Sickness.

INTRODUCTION: A theory is presented to explain the major findings regarding motion sickness and to synthetize current theories concerning its etiology. The theory proposes that an imbalance in the output of the two major organs of the labyrinth-favoring the semicircular canals over the otolith organs-is responsible for most instances of motion sickness as experienced in terrestrial and microgravity environments. METHODS: Strengths and limitations of current theories are first outlined before the different roles of the canals and otoliths in the genesis of motion sickness symptoms are described. RESULTS: The proposed theory is shown to explain a large number of findings and integrate current theories. DISCUSSION: The role of vestibular imbalance in motion sickness may be a consequence of the more general differences between the canals and otoliths in autonomic control.Previc FH. Intravestibular balance and motion sickness. Aerosp Med Hum Perform. 2018; 89(2):130-140.

Subjective Vertical Conflict Theory and Space Motion Sickness.

BACKGROUND: Space motion sickness (SMS) remains a troublesome problem during spaceflight. The subjective vertical (SV) conflict theory postulates that all motion sickness provoking situations are characterized by a condition in which the SV sensed from gravity and visual and idiotropic cues differs from the expected vertical. This theory has been successfully used to predict motion sickness in different vehicles on Earth. METHOD: We have summarized the most outstanding and recent studies on the illusions and characteristics associated with spatial disorientation and SMS during weightlessness, such as cognitive map and mental rotation, the visual reorientation and inversion illusions, and orientation preferences between visual scenes and the internal z-axis of the body. RESULTS: The relationships between the SV and the incidence of and susceptibility to SMS as well as spatial disorientation were addressed. CONCLUSION: A consistent framework was presented to understand and explain SMS characteristics in more detail on the basis of the SV conflict theory, which is expected to be more advantageous in SMS prediction, prevention, and training.

The Use of Release-Active Antibody-Based Preparations for Vertigo Prevention in Adults.

The effectiveness of antibody-based release-active preparations Impaza (antibodies to eNOS), Tenoten (antibodies to brain-specific protein S-100), Dietressa (antibodies to type 1 cannabinoid receptor), Brizantin (combined preparation, antibodies to brain-specific protein S-100 and type 1 cannabinoid receptor), and Divaza (combined preparation, antibodies to brain-specific protein S-100 and eNOS) in the prevention of vertigo was studied on the model of intermittent accumulation of Coriolis accelerations (ICCA). Modification of activity of vestibular receptors and signal systems by release-active preparations contributed to an increase in ICCA tolerance time. Combined preparation Impaza possessed the most significant antinaupathic properties. Brizantin was less potent in this respect.

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.

Space motion sickness and motion sickness: symptoms and etiology.

The adverse symptoms of space motion sickness (SMS) have remained problematic since the beginning of manned spaceflight. Despite over 50 yr of research SMS remains a problem that affects about half of all space travelers during the first 24-72 h of a spaceflight. SMS has been treated as another form of motion sickness (MS) despite distinct differences in symptomology. In this review SMS and MS differences are examined and documented based on available data. Vestibular biomechanics that occur during weightlessness coupled with theoretical assertions regarding human evolution have led us to propose a two-component model of SMS. The first component involves conflicting sensory signals inherent to the otolith organs that occur during weightlessness. The second component is a bimodal conflict between the otoliths and semicircular canals that can occur during normal head movements in weightlessness. Both components may inadvertently, and mistakenly, signal that a vestibular malfunction has occurred, hence initiating a protective mechanism that may produce symptoms that discourage activity.

[The pathogenetic approach to the development of tools and methods for the improvement of statokinetic stability in the operators of aerospace systems].

The objective of the present study was to estimate the efficacy of the tools and methods for the optimization of the activity of the central nervous system (CNS) and analyzers involved in the maintenance of the statokinetic (SK) stability in man. To this effect, we evaluated the outcome of bemitil treatment during 10 days with and without A.I. Yarotsky test and the influence of these procedures on the pathophysiological characteristics of selected elements of the work of operators of aerospace systems. Based on the data obtained in the study, the tools and methods have been developed that allow the efficacy and quality of certain aspects of the operators' activity to be improved, viz. general working capacity under conditions requiring enhanced statokinetic stability, self-confidence, emotional and somatic comfort.

Pharmaceutical countermeasures have opposite effects on the utricles and semicircular canals in man.

INTRODUCTION: Sensory conflicts in the vestibular system lead to motion sickness of which space motion sickness (SMS) is a special case. SMS affects up to 70% of the astronauts during the first 3 days in space. The search for effective countermeasures has led to several nonpharmacological and pharmacological approaches. The current study focuses on the effects of lorazepam (1 mg), meclizine (25 mg), promethazine (25 mg), and scopolamine (0.4 mg) on the vestibular system, with special focus on the canal and otolith functions separately. METHODS: The study had a placebo-controlled, single blind, repeated measures design. Sixteen healthy volunteers were subjected to a total of 7 test sessions, the first and last being without intake of medication. Semicircular canal function was evaluated by means of electronystagmography and otolith function with unilateral centrifugation. The horizontal semicircular canal function was characterized by the vestibulo-ocular reflex (VOR) gain measured during earth vertical axis rotation as well as the total caloric response. The function of the utricles was represented by the utricular sensitivity, reflecting the ocular counter roll relative to the virtual induced head tilt. RESULTS: Promethazine significantly decreased the semicircular canal and utricular parameters. Both scopolamine and lorazepam caused only a decrease in the utricular sensitivity, whereas meclizine only decreased the semicircular canal-induced VOR gain. DISCUSSION: The results show that the drugs affected different areas of the vestibular system and that the effects can thus be attributed to the specific pharmacological properties of each drug. Meclizine, as an antihistaminergic and weak anticholinergic drug, only affected the VOR gain, suggesting a central action on the medial vestibular nucleus. The same site of action is suggested for the anticholinergic scopolamine since acetylcholine receptors are present and utricular fibers terminate here. The global vestibular suppression caused by promethazine is probably a consequence of its anticholinergic, antihistaminergic, and antidopaminergic properties. Based on the fact that lorazepam increased the affinity of gamma-aminobutyric acid (GABA) for the GABA(A)-receptor and its effects on the utriculi, the site of action seems to be the lateral vestibular nucleus. CONCLUSION: Meclizine, scopolamine, and lorazepam selectively suppress specific parts of the vestibular system. Selective suppression of different parts of the vestibular system may be more beneficial for alleviating (space) motion sickness than general suppressive agents. Additionally, this knowledge may help the clinician in his therapeutic management of patients with either semicircular canal or otolith dysfunction.

Effect of daily linear acceleration training on the hypergravity-induced vomiting response in house musk shrew (Suncus murinus).

The effects of repeated linear acceleration training and the antimotion sickness drug, promethazine, on hypergravity-induced motion sickness were examined in musk shrew (Suncus murinus), which is known to show a vomiting response to motion stimulation. Animals were assigned into five groups: vestibular intact, untreated animals (Sham), vestibular lesioned (VL) animals, vestibular intact animals with promethazine hydrochloride administered as daily drinking water (Prom), vestibular intact animals who underwent horizontal linear accelerator motion training (Train), and vestibular intact animals treated with both promethazine hydrochloride and linear acceleration training (Prom+Train). In Sham animals, the number of vomiting episodes was 14±2 during 2 G exposure for 10min, and was accompanied by intense Fos expression in the medial vestibular nucleus (MVe), the nucleus of the solitary tract (NTS), the area postrema (AP), and the paraventricular hypothalamic nucleus (PVN). The vomiting response and Fos expression were completely abolished in VL animals, indicating that these responses are mediated via the vestibular system. Although Train and Prom animals experienced a significantly reduced number of hypergravity-induced vomiting episodes compared with Sham animals, the effect was significantly greater in Train animals than in Prom animals. Fos expression in the NTS, AP, and PVN were significantly more reduced in Train animals than in Prom animals. Higher dose of bolus injection of promethazine (50mg/kg, i.p.) completely abolished the vomiting episodes, although the animals were drowsy and sedated due to side effects. In conclusion, daily linear acceleration training and promethazine could prevent the hypergravity-induced vomiting episodes.

A re-investigation of the role of utricular asymmetries in Space Motion Sickness.

During the first days of spaceflight, about 50-70% of the astronauts experience symptoms of Space Motion Sickness (SMS). It has been proposed that an asymmetry between the left and right otolith organs contributes to an astronaut's individual susceptibility. A recently developed test to measure unilateral utricular function enabled us to re-investigate this so-called otolith asymmetry hypothesis, while using the paradigm of sustained centrifugation as a ground based model for SMS. This latter paradigm has been shown to elicit symptoms similar to those of SMS and is referred to as Sickness Induced by Centrifugation (SIC). In 15 healthy subjects unilateral utricular function was assessed by recording ocular counter rolling during a unilateral centrifugation paradigm. In addition, saccular function was assessed by recording Vestibular Evoked Myogenic Potentials (VEMPs), and horizontal semicircular canal function was assessed using bithermal caloric stimulation. SIC-susceptible subjects showed a marginally higher degree of utricular asymmetry, utricular sensitivity and semicircular canal sensitivity (p < 0.1) than the non-susceptible group. Interestingly, a logistic regression model using both utricular and semicircular canal parameters led to a correct classification of 91% of the subjects. As such, these results suggest that otolith asymmetry is at most one factor - and not present in all susceptible subjects - in defining susceptibility to SMS and SIC. Both the utricular and the canal system might be involved as well.

A rationale for space motion sickness.

Space motion sickness (SMS) still remains a problematic nuisance for a majority of fliers during their first 1 to 3 days in space and is an enigma to all concerned after almost half a century of spaceflight and extensive ground and in-flight studies. There is no known etiology consistent with observed signs and symptoms, and attempts to produce pre- and in-flight countermeasures have largely failed. Some medications for motion sickness (MS) have been partially effective, but must be used with caution due to their side effects. A hypothesis regarding SMS that is consistent with current knowledge of vestibular physiology and with observed and measured phenomena during SMS is presented.

The effect of parabolic flight on perceived physical, motivational and psychological state in men and women: correlation with neuroendocrine stress parameters and electrocortical activity.

Previous findings of decreased mental and perceptual motor performance during parabolic flights have been attributed mainly to the primary effects of weightlessness rather than the accompanying effects of stress and altered mood. Although recent studies have alluded to the possible negative effects of stress on performance, there has been no attempt to investigate this during parabolic flights. Over a period of 3 years, 27 human participants (male n = 18, mean age +/- SD 34.67 +/- 7.59 years; female n = 9, 36.22 +/- 9.92 years) were recruited with the aim to evaluate if, and to what extent, parabolic flights are accompanied by changes in mood. Furthermore, the relationships between mood and physiological markers of stress and arousal, namely circulating stress hormones (ACTH, cortisol, epinephrine, norepinephrine, prolactin and brain activity (EEG)) were investigated. A strong and significant correlation was found between circulating stress hormone concentrations and perceived physical state, motivational state (MOT) and psychological strain (PSYCHO), whereas no interaction between mood and EEG or EEG and stress hormone concentrations was observed. Therefore, two different stress responses appear to be present during parabolic flight. The first seems to be characterised by general cortical arousal, whereas the second seems to evolve from the adrenomedullary system. It is likely that both these mechanisms have different effects on mental and perceptual motor performance, which require further investigation and should to be taken into account when interpreting previous weightlessness research.

Velocity storage activity is affected after sustained centrifugation: a relationship with spatial disorientation.

Prolonged exposure to hypergravity in a human centrifuge can lead to post-rotary spatial disorientation and motion sickness. These symptoms are mainly provoked by tilting head movements and resemble the Space Adaptation Syndrome. We hypothesized that the occurrence of these post-rotary effects might be related to changes in the velocity storage (VS) mechanism, which is suggested to play an important role in spatial orientation. In particular, we investigated whether the re-orientation of the eye velocity vector (EVV) towards gravity during off-vertical optokinetic stimulation was affected by centrifugation. Twelve human subjects were exposed to a hypergravity load of 3G (G-load directed along the naso-occipetal axis) for a duration of 90 min. Before and after centrifugation we recorded optokinetic nystagmus (OKN) elicited by a stimulus pattern moving about the subject's yaw axis, with the head erect and tilted 45 degrees to both sides. During OKN with the head erect, we observed a pitch-down component, reorienting the EVV on average 4.5 degrees (SD 3.6, pretest values) away from the stimulus axis. Head tilt induced an additional shift of the EVV towards the spatial vertical of 6.4 degrees on average (SD 3.2). This head-tilt induced reorientation was significantly decreased after centrifugation to 4.7 degrees (SD 2.9), suggesting a reduction of VS-activity. By means of a vector model we estimated the reduction in VS-activity at 31%. Such a decrease in VS-activity might reflect a deterioration of the ability to integrate sensory signals to obtain an estimate of gravity during tilting head movements, resulting in motion sickness in susceptible subjects.

Modeling intracranial pressures in microgravity: the influence of the blood-brain barrier.

INTRODUCTION: A majority of astronauts experience symptoms of headache, vomiting, nausea, lethargy, and gastric discomfort during the first few hours or days after entering a microgravity environment. Due to similarities in symptoms and their time evolution, it has been hypothesized that some of these conflicts are related to the development of benign intracranial hypertension in these individuals in microgravity. METHODS: This hypothesis was tested using a validated mathematical model that embeds the intracranial system in whole-body physiology. This model was used to predict steady-state intracranial pressures in response to various cardiovascular stimuli associated with microgravity, including changes in arterial pressure, central venous pressure, and blood colloid osmotic pressure. The model also allowed alterations of the blood-brain barrier due to factors such as gravitational unloading and increased exposure to radiation in space to be considered. RESULTS: Simulations predicted that intracranial pressure will increase significantly if, combined with a drop in blood colloid osmotic pressure, there is a reduction in the integrity of the blood-brain barrier in microgravity. DISCUSSION: These results suggest that in some otherwise healthy individuals microgravity environments may elevate intracranial pressure to levels associated with benign intracranial hypertension, producing symptoms that can adversely affect crew health and performance.

Adaptation to motion sickness from torso rotation affects symptoms from supine head nodding.

INTRODUCTION: Space motion sickness affects more than 50% of astronauts. Adaptation to one kind of nauseogenic motion can affect the response to another. We hypothesized that repeated exposure to torso rotation (TR) would diminish motion sickness (MS) due to supine head nodding (HN), a ground-based analogue for space sickness. METHODS: During TR, standing subjects swept their gaze back and forth between two targets located 135 degrees to either side of straight ahead. For HN, the subject lay supine on a platform with his/her head and neck hanging over the edge. The head was pitched back and forth between the horizontal position and rotated back as far as possible. MS was quantified in 5 male and 20 female subjects using numerical estimates of discomfort and a more detailed questionnaire. Susceptibility to TR and HN was determined on three occasions for each stimulus. At least 1 mo separated any two tests. Subjects were exposed to TR once a day for 7 consecutive days 1 mo after the final control session. Within 24 h of the seventh session, and 1 mo later, susceptibility to HN was evaluated again. RESULTS: There was a significant decrease in MS susceptibility during repeated exposure to TR (time to stop 17.7 min on Day 1, 31.8 min on Day 7). In contrast, there was a significant increase in MS susceptibility to HN after repeated exposure to TR (mean time to stop 11.7 min before TR, 9.5 min after). Susceptibility to HN was back to normal (time to stop 11.4 min) 1 mo later. DISCUSSION: Subjects can adapt to TR by repeated exposure. At the same time, susceptibility to HN increases. Strategies for pre-adaptation to space motion sickness need to be chosen carefully as they could actually be counterproductive.

Sickness induced by head movements after different centrifugal Gx-loads and durations.

It has been found that sustained centrifugation on Earth may evoke sickness symptoms that are similar to those of the Space Adaptation Syndrome (SAS). As in SAS, incidence of this 'Sickness Induced by Centrifugation' (SIC) is about 50% and the symptoms are particularly evoked by head movements. By systematically varying the G-load and duration of centrifugation, the current study investigated the characteristics of the gravitational stimulus that is required for SIC to occur. Subjects were exposed to centrifugation at 2 and 3Gx, for a duration of 45 and 90 minutes. A standardized head movement protocol was used to evoke SIC after centrifugation. The results show that in six out of 12 subjects (50%) no serious symptoms were elicited. In the remaining subjects, the effects of the 3G runs exceeded those of the 2G runs, and within each G-level symptom intensity was higher for the 90 min than for the 45 min exposure. An exponential fit on this data showed that the time constant of adaptation to the gravitational stimulus was about 60 minutes. This suggests that short duration exposures (i.e. <60 min) are not likely to induce serious SIC.