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NASA NTRS1992

Catecholaminergic responses to stressful motion stimuli, scopolamine plus amphetamine, and dexamethasone

Peripheral levels of epinephrine (EPI) and neoepinephrine (NE) generally rise following stressful motion stimuli. Effective anti-motion sickness drugs, scopolamine plus, d-amphetamine (S/D) and dexamthasone (DEX) modulate release of EPI and NE. This modulation may be of etiological relevance. Methods: Severe nausea was induced by exposure to coriolis simulation using a rotating chair. Chronic administration of S/D (0.4 and 5 mg/da) DEX (3 mg/day) and placebo preceded coriolis simulation. EPI and NE were measured immediately before and after simulation. A double-blind crossover design was used. Results: Nausea-induced elevations of EPI (2.5 fold, p less than .01) and NE were not diminished upon repeated exposure and adaptation to the stressor. Subjects with more pronounced elevations of EPI following simulation displayed higher resistance to stressful motion (p less .05). Alteration of peripheral catechlomaine levels following drug suggested that motion sickness was not mediated by peripheral catechlolamine receptor simulation. EPI and NE levels were 2.8 and 3.6-fold higher (p less than .03 and .01) after nausea without DEX treatment. DEX loading halved pre-stress levels of EPI and NE (p less than .05). Conclusions: Marked differences were noted in individual responses to drug and systematic responses of EPI and NE. It is possible that the responses of EPI to motion sickness may predict resistance to stressful motion and represent a peripheral manifestation of some as yet unknown central event of etiologic relevance.

Kohl, R. L.↗

NASA NTRS2012

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

Putcha, Lakshmi↗

NASA NTRS1983

Physiological and behavioral effects of tilt-induced body fluid shifts

This paper addresses the 'fluid shift theory' of space motion sickness. The primary purpose of the research was the development of procedures to assess individual differences in response to rostral body fluid shifts on earth. Experiment I examined inner ear fluid pressure changes during head-down tilt in intact human beings. Tilt produced reliable changes. Differences among subjects and between ears within the same subject were observed. Experiment II examined auditory threshold changes during tilt. Tilt elicited increased auditory thresholds, suggesting that sensory depression may result from increased inner ear fluid pressure. Additional observations on rotation magnitude estimation during head-down tilt, which indicate that rostral fluid shifts may depress semicircular canal activity, are briefly described. The results of this research suggest that the inner ear pressure and auditory threshold shift procedures could be used to assess individual differences among astronauts prior to space flight. Results from the terrestrial observations could be related to reported incidence/severity of motion sickness in space and used to evaluate the fluid shift theory of space motion sickness.

Parker, D. E.↗

NASA NTRS1985

Sensory and motor properties of the cerebellar uvula and modulus

The uvula and nodulus (vermal lobules 9 and 10) of the vestibulocerebellum are implicated by behavioral evidence in the control of eye and head movements and in the production of motion sickness. The uvula and nodulus could play a role in these functions through known output pathways. Purkinje cells in both structures project via the fastigial and vestibular nuceli to the ventral horn of the cervical spin cord, to oculomotor neurons, and to the emetic region of the reticular formation (ablation of which abolishes susceptability to motion sickness). Uvula and nodulus Purkinje cells will be analyzed in cats trained to make controlled head movements. The activity of these neurons is expected to modulate well during head and/or eye movements because the uvula and nodulus receive heavy projections from sources of visual, vestibular and neck proprioceptive information. How neuron activity contributes to movement and how different sensory inputs converge to influence this contribution may be determined by characterizing movement related properties of these neurons. A population of neurons that modulates powerfully to the conflict between different head movement signals that can cause motion sickness may be identified.

Robinson, F. R.↗

NASA NTRS1988

Ocular torsion in upright and tilted positions during hypo- and hypergravity of parabolic flight

Four subjects considered resistant to motion sickness were tested in KC-135 parabolic flight to examine ocular torsion at hypo-gravity and hypergravity. Three of these subjects showed no significant torsion at zero G in either the upright position or when tilted 30 deg to right or left. At 1.8 G in the tilted positions, they showed greater ocular counterrolling than at 1 G. None of these three subjects became motion sick. The fourth subject showed eye torsion toward his left in all positions at zero G. This leftward bias could also be seen at 1.8 G when tilted left ear down, the side that induces rightward counterrolling. There he had less eye torsion than at 1 G. This subject became motion sick. These results support the hypothesis that asymmetry of the utricular system may be well compensated in the normal 1 G environment, but unmasked in unaccustomed gravitational situations, suggesting a possible predictive test for space adaptation syndrome.

Diamond, Shirley G.↗

NASA NTRSDate not supplied

Characterizing the Risk: Review of Sensorimotor Evidence and Research Roadmap

BACKGROUND: NASA’s Artemis program will take astronauts back to the lunar surface for the first time in almost 50 years. Despite the successes of the previous Apollo program, the Artemis missions will differ in duration, vehicle characteristics, and landing tasks that may exacerbate the risks to crew health/safety and mission objectives. NASA’s Human Research Program identifies the risk of altered sensorimotor/vestibular function impacting critical mission tasks as one of the top priority risks to lunar exploration missions. This session will review the existing evidence and remaining gaps in knowledge for the sensorimotor risk. DESCRIPTION: Alterations in sensorimotor processing during spaceflight can lead to motion sickness, spatial disorientation, and decrements in postural control, locomotion, and fine motor control during and following gravity-transitions. The risk of impairment is greatest during and soon after gravity-transitions, when performance decrements may have high operational impacts (e.g., manual landings, immediate egress following landing, and early extravehicular activities (EVAs)). Recent studies have specifically improved the risk characterization of changes in perception, motion sickness, postural and locomotor control, manual control, and fine-motor coordination. However, given the difficulty in obtaining measurements during and soon after gravity-transitions, evidence for initial decrements immediately following gravity-transitions remains limited. The most significant gaps in the risk include manual control ability around gravity-transitions, the incidence and severity of motion sickness during landings, and the ability to perform egress/EVAs soon after gravity-transition. To address these gaps, current research roadmaps leverage both spaceflight studies and ground-based analogs for risk characterization and countermeasure development/validation. DISCUSSION: This panel will further describe the current sensorimotor research strategies with an emphasis on the operational scenarios of manual control, crew egress, and EVA. The goal of this research is to accommodate the needs of the crew and facilitate human capabilities to ensure lunar mission success. This work will prepare NASA for successful Artemis missions and enable the next giant leap, the exploration of Mars.

Timothy Ryan Macaulay↗

NASA NTRS1990

Autogenic-feedback training - A treatment for motion and space sickness

A training method for preventing the occurrence of motion sickness in humans, called autogenic-feedback training (AFT), is described. AFT is based on a combination of biofeedback and autogenic therapy which involves training physiological self-regulation as an alternative to pharmacological management. AFT was used to reliably increase tolerance to motion-sickness-inducing tests in both men and women ranging in age from 18 to 54 years. The effectiveness of AFT is found to be significantly higher than that of protective adaptation training. Data obtained show that there is no apparent effect from AFT on measures of vestibular perception and no side effects.

Cowings, Patricia S.↗

NASA NTRS1978

Bidirectional overadaptation achieved by executing leftward or rightward head movements during unidirectional rotation

Nine college age males, all prone to motion sickness, were subjects in an experiment designed to test adaptation to motion. Subjects were placed in a slow rotation room (SRR) for varying intervals and asked to perform headward movements. Degree of adaptation to the SRR was measured in the framework of 3 categories: reduction of ataxia, reduction of oculogyral illusion, and reduction of epiphenomena, which includes symptoms of motion sickness. 'Satisfactory' adaptation was acquired and retained in 7 of the 9 subjects. Tables are presented summarizing the results.

Graybiel, A.↗

NASA NTRS2017

MS Non-Pharmacological Countermeasure to Decrease Landing Sickness and Improve Functional Performance While Disorientad

Upon return from spaceflight, a majority of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. No operational countermeasure currently exists to mitigate the risks associated with these sensorimotor disturbances. Stochastic resonance (SR) can be thought of simply as "noise benefit" or an increase in information transfer by a system when in the presence of a non-zero level of noise. We have shown that low levels of stochastic vestibular stimulation (SVS) improve balance and locomotor performance due to SR (Goel et al. 2015, Mulavara et al. 2011, 2015). Additionally, a study in a 6-hydroxydopamine (6-OHDA) hemi-lesioned rat model of Parkinson's disease demonstrated improvements in locomotor activity after low-level SVS delivery possibly due to an increase in nigral gamma-aminobutyric acid (GABA) release in a dopamine independent way (Samoudi et al. 2012). SVS specifically increased GABA release on the lesioned, but not the intact side. These results suggest that SVS can cause targeted alterations of GABA release to affect performance of functional tasks. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008). Magnusson et al. (2000) supported this finding by showing that the administration of a GABAB agonist caused a reversal of the symptoms that is normally seen after unilateral labyrinthectomy. Thus, GABA could play a significant role in reducing MS and promoting adaptability. We have taken advantage of the SR mechanism as a modulator of neurotransmitters to develop a unique SVS countermeasure system to mitigate MS symptoms and improve functional performance after landing. Healthy subjects (n=20) participated in two test sessions, one in which they received +/-400 microA of SVS and one where they received no stimulation (0 microA); the study design was counterbalanced. Subjects began by performing a series of four functional tasks 3-5 times as baseline measurements of task performance. Then, to induce MS, subjects walked an obstacle course with up-down reversing prisms. If they completed the course before achieving our pre-determined level of MS, they were asked to read a poster while making large up-down head movements to a metronome while still wearing the reversing prism goggles. Subjects were stopped every two minutes and asked to report their MS symptoms. Using the Pensacola Scale for motion sickness, test operators evaluated the level of MS of each subject. Once a subject reached an 8 on this scale, which is equivalent to mild malaise, or 30 minutes had passed since the start of the MS induction, this protocol was stopped. Finally, immediately after MS induction, subjects were asked to complete the four functional tasks again. Although, 100% of our subjects experienced at least one MS symptom, only 55% of our subjects experienced stomach awareness to any degree. Without SVS, only 40% of subjects lasted the full 30-minute MS induction protocol, while 65% of subjects lasted the full 30 minutes with SVS, which is nearly a significant increase (p=0.056). In addition, subjects showed significant improvement from baseline when performing a tandem walk and a prone-to-stand test immediately after the MS induction protocol was stopped but the stimulation level was continued. The results are promising and future work includes comparing MS progression between PMZ and SVS directly in subjects that are provoked to a minimum of nausea. Low levels of SVS stimulation may serve as a non-pharmacological countermeasure to replace or reduce the PMZ dosage requirements and concurrently improve functional performance during transitions to new gravitational environments after spaceflight.

Rosenberg, M. J. F.↗

NASA NTRS1991

Illusory self motion and simulator sickness

Presented here is a discussion of simulator sickness (with applications to motion sickness and space sickness) based on the notion of senses as perceptual systems, and the sensory conflict theory. Most forms of the sensory conflict theory unnecessarily propose the existence of a neural store. The neural store is thought to consist of a record of previous perceptual experiences against which currently experienced patterns of stimulation are compared. The authors seek to establish that in its most parsimonious form the sensory conflict theory does not require a construct such as the neural store. In its simpler form, the sensory conflict theory complements and extends Gibson's view of the senses as perceptual systems.

Hettinger, Lawrence J.↗

NASA NTRS1976

Airborne testing of three antimotion sickness preparations

Thirteen human volunteers were exposed to weekly flights in which standardized, steep turns were used to produce motion sickness. A combination of promethazine hydrochloride (25 mg) plus ephedrine sulphate (25 mg) was found to be equally as effective as the combination of 1-scopolamine hydrobromide (0.35 mg) plus d-amphetamine sulphate (5 mg). Droperidol (2.5 mg) was indistinguishable from the placebo. It was concluded that the treatment of choice for motion sickness is promethazine plus ephedrine.

Johnson, W. H.↗

NASA NTRS1988

Comparison of efficacy of ginger with various antimotion sickness drugs

Ginger and several other medications were compared with scopolamine and d-amphetamine for effectiveness in prevention of motion sickness. Methods: Double-blind techniques were used. The subjects were given the medications two hours before they were rotated in a chair making head movements until a symptom total short of vomiting was reached. Standardized N.A.S.A. techniques were used for speed of rotation and end-point of motion sickness. Results: The three doses of ginger were all at the placebo level of efficacy. Amitriptyline, ethopropazine and trihexyphenidyl increased the tolerated head movements but the increase was not statistically significant. Significant levels of protection were produced by dimenhydrinate, promethazine, scopolamine and d-amphetamine. Protection was further increased by combination of these latter drugs with d-amphetamine. Efficacy was greatest as the dose was increased. Conclusions: The medication of choice in this study was scopolamine 0.6 mg with d-amphetamine 10 mg. This combination provided good protection with acceptable side effects.

Non-NASA Center↗

NASA NTRS1986

Preadapting to Weightlessness

Report discusses physiological and physical concepts of proposed training system to precondition astronauts to weightless environment. System prevents motion sickness, often experienced during early part of orbital flight. Also helps prevent seasickness and other forms of terrestrial motion sickness, often experienced during early part of orbital flight. Training affects subject's perception of inner-ear signals, visual signals, and kinesthetic motion perception. Changed perception resembles that of astronauts who spent many days in space and adapted to weightlessness.

Reschke, M. F.↗

NASA NTRS1980

Effect of Ablation of Area Postrema on Frequency and Latency of Motion Sickness-Induced Emesis in the Squirrel Monkey

Twelve young adult squirrel monkeys of the Bolivian subspecies were subjected to continuous counter-clockwise horizontal rotary motion at 25 rpm, together with a sinusoidal vertical excursion of 6 in. every 2 sec (0.5 Hz). Each animal was exposed to this motion regimen for a period of 60 min once each week for three consecutive weeks. Following the third weekly motion test bilateral ablation of the Area Postrema (AP) was performed in eight of the animals by thermal cautery. Two control animals were sham-operated after the third motion test while two additional controls were given the motion tests as noted above but were not operated. The four controls were considered as a single group for statistical analyses of results of the motion tests. After a recovery period of 30 to 40 days, and at a comparable interval in the non-operated controls, each animal was again tested for motion sensitivity for three consecutive weeks. The brains of all of the animals were then fixed by left ventriculal cardiac perfusion with Bouin's fluid and processed for histological evaluation of the bilateral AP ablation in comparison with the control brains. Five of the AP-ablated animals postoperatively were completely refractory to the motion stimuli, two exhibited a decreased number of emetic responses, and one exhibited the same number of responses before and after the AP lesions. The controls exhibited no significant difference in emetic sensitivity on the second series of three weekly tests than on the first series. The results of this investigation appear to be in agreement with the observations of Wang and Chinn in the dog indicating that the integrity of the AP (CTZ) is essential to the emetic response to motion.

Brizzee, K. R.↗

NASA NTRSDate not supplied

Neuro-Vestibular Examination During and Following Spaceflight (Vestibular Health)

BACKGROUND Adaptation to microgravity during spaceflight causes neurological disturbances that are either directly or indirectly mediated by the vestibular system. These disturbances could include space motion sickness, spatial disorientation, and cognitive impairment, as well as changes in head-eye coordination, vestibulo-ocular reflexes, and control of posture and locomotion. Otolith-mediated reflex gains appear to adapt rapidly during spaceflight and after landing. However, animal studies have shown that structural modifications of the vestibular sensory apparatus develop during long-duration spaceflight. To date, no studies have characterized the severity of vestibular syndromes experienced by astronauts as a function of the duration of spaceflight or whether the effects are caused by changes at the peripheral end organs, midbrain, cerebellum, or vestibular cortex. OBJECTIVES We will investigate temporal vestibular changes in crewmembers of short, 6-month, and one-year missions to identify trends in adaptation of vestibular health and performance in orbit and after landing. We will also determine whether the vestibular organs and/or the central vestibular system undergo structural changes during long-duration exposure to microgravity, which could cause vestibular disorders when transitioning to a different gravitational environment. METHODS Recordings of eye, head, and body movements, as well as subjective reports of perception of motion, will be used to determine the presence of abnormal eye movements, dysmetria, motion sickness symptoms, and illusions of motion during head or body movements. This includes characterization of temporal trends in central compensation for vestibular (otolith) asymmetry. Pre-flight data will be collected 90 days before the flight. In-flight tests will be performed early in the mission and once every one or two months thereafter. Post-flight examinations will be performed on the following days after return (R) from the mission: R+0, R+4, R+9, and R+30. Ground-based control tests will be performed on healthy volunteers in the laboratory to estimate mean normative responses. CONTROL RESULTS Thirty-two healthy (non-astronaut) control subjects performed the same ground test procedures as planned for crewmembers. In addition to establishing a normative database, these data were used to calculate vestibular asymmetries from perceptual reports during unilateral centrifugation, oculomotor responses during visual-alignment tasks, vestibulo-ocular reflex gain during head-impulse tests, and body rotation during stepping tests. A significant correlation was observed between asymmetries of subjective visual vertical and verbal report during unilateral centrifugation. Another significant correlation was observed between the asymmetries of ocular alignment, vestibulo-ocular reflex gain, and body rotation. These findings in a healthy cohort may help us better understand changes in vestibular asymmetries in crewmembers during and following spaceflight. RELEVANCE If the observed symptoms in crewmembers are more deleterious after the year-long missions than those documented after 6-month missions, then relevant countermeasures will be required to maintain the health and operational performance of astronauts during longer missions. Depending on the etiology of the vestibular syndrome revealed by these tests, countermeasures will be proposed based on vestibular rehabilitation therapies currently used in patients with vestibular disorders, such as habituation, gaze stabilization, and/or balance training exercises. ACKNOWLEDGEMENT This work is supported by the NASA’s Human Research Program Human Health Countermeasures Element.

T R Macaulay↗

NASA NTRSDate not supplied

Neuro-Vestibular Examination During and Following Spaceflight (Vestibular Health)

BACKGROUND Adaptation to microgravity during spaceflight causes neurological disturbances that are either directly or indirectly mediated by the vestibular system. These disturbances can include space motion sickness, spatial disorientation, and cognitive impairment, as well as changes in head-eye coordination, vestibulo-ocular reflexes, and control of posture and locomotion. Otolith-mediated reflex gains appear to adapt rapidly during spaceflight and after landing. However, animal studies have shown that structural modifications of the vestibular sensory apparatus develop during long-duration spaceflight. To date, no studies have characterized the severity of vestibular syndromes experienced by astronauts as a function of the duration of spaceflight or whether the effects are caused by changes at the peripheral end organs, midbrain, cerebellum, or vestibular cortex. OBJECTIVES We will investigate temporal vestibular changes in crewmembers of short, 6-month, and one-year missions to identify trends in adaptation of vestibular health and performance in orbit and after landing. We will also determine whether the vestibular organs and/or the central vestibular system undergo structural changes during long-duration exposure to microgravity, which could cause vestibular disorders when transitioning to a different gravitational environment. METHODS Recordings of eye, head, and body movements, as well as subjective reports of perception of motion, will be used to determine the presence of abnormal eye movements, dysmetria, motion sickness symptoms, and illusions of motion during head or body movements. This includes characterization of temporal trends in central compensation for vestibular (otolith) asymmetry. Pre-flight data will be collected 90 days before launch. In-flight examinations will be performed early in the mission (Flight Days 1 and 30) and once every two or three months thereafter. Post-flight examinations will be performed on the following days after return (R) from the mission: R+0, R+4, R+9, and R+30. Ground-based control tests have been performed on healthy volunteers in the laboratory to estimate mean normative responses. RESULTS Data collection for this study is ongoing. Data processing techniques are being refined. Our eye tracking method for measuring three-dimensional eye movement takes advantage of modern computer vision software (OpenCV) and advances in the field of iris recognition to improve measurement of ocular-counterolling. RELEVANCE If the observed symptoms in crewmembers are more deleterious after the year-long missions than those documented after 6-month missions, then relevant countermeasures will be required to maintain the health and operational performance of astronauts during longer missions. Depending on the etiology of the vestibular syndrome revealed by these tests, countermeasures will be proposed based on vestibular rehabilitation therapies currently used in patients with vestibular disorders, such as habituation, gaze stabilization, and/or balance training exercises.

T R Macaulay↗

NASA NTRS2001

Configural Scoring of Simulator Sickness, Cybersickness and Space Adaptation Syndrome: Similarities and Differences?

From a survey of ten U.S. Navy flight simulators a large number (N > 1,600 exposures) of self-reports of motion sickness symptomatology were obtained. Using these data, scoring algorithms were derived, which permit examination of groups of individuals that can be scored either for 1) their total sickness experience in a particular device; or, 2) according to three separable symptom clusters which emerged from a Factor Analysis. Scores from this total score are found to be proportional to other global motion sickness symptom checklist scores with which they correlate (r = 0.82). The factors that surfaced from the analysis include clusters of symptoms referable as nausea, oculomotor disturbances, and disorientation (N, 0, and D). The factor scores may have utility in differentiating the source of symptoms in different devices. The present chapter describes our experience with the use of both of these types of scores and illustrates their use with examples from flight simulators, space sickness and virtual environments.

Kennedy, Robert S.↗

NASA NTRS2003

Virtual Reality Training: "Cybersickness" and Effects on Sensorimotor Functions

The overall goal of this study is to examine the extent to which exposure to virtual reality (VR) systems produces motion sickness and disrupts sensorimotor functions. Two of the major problems in using VRs are: 1) potential "cybersickness", a form of motion sickness, and 2) maladaptive sensorimotor coordination following virtual environment (VE) training. It is likely that users will eventually adapt to any unpleasant perceptual experiences in a virtual environment. However the most critical problem for training applications is that sensorimotor coordination strategies learned in the VE may not be similar to the responses required in the real environment. This study will evaluate and compare responses to the two types of VR delivery systems (head-mounted display [HMD] and a dome-projection system [DOME]), two exposure duration periods (30 minutes or 60 minutes), and repeated exposures (3 sessions). Specific responses that we will examine include cybersickness severity and symptom patterns, and several sensorimotor functions (eye-hea.d and eye-head-hand coordination, and postural equilibrium). To date, all hardware and software acquisition, development, integration and testing has been completed. A database has been developed and tested for the input, management and storage of all questionnaire data. All data analysis scripts have been developed and tested. Data was collected from 20 subjects in a pilot study that was conducted to determine the amount of training necessary to achieve a stable performance level. Seven subjects are currently enrolled in the study designed to examine the effects of exposure to VE systems on postural control. Data has been collected from two subjects, and it is expected that the results from ten subjects will be presented.

Harm, Deborah L.↗