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Space motion sickness
Acta Astronautica Vol. 6, pp. 1259-1272 Pergamon Press Ltd., 1979. Printed in Great Britain
Space motion sickness J. L. H O M I C K Medical Sciences Division, NASA-Johnson Space Center, Houston, TX 77058, U.S.A.
(Received 10 January 1978) Abstract--Space motion sickness, presumably triggered by sudden entry into a weightless environment, occurred with unexpected frequency and severity among astronauts who flew the Skylab missions. Recovery from symptoms was complete within 3-5 days, and as revealed by the Skylab MI31 Human Vestibular Function Experiment, all crewmembers were immune to experimentally induced motion sickness after mission day 8. This syndrome has been recognized as a possible threat to the early mission well-being and operational efficiency of at least some individuals who will fly space missions in the future. The causes of space motion sickness are not clearly understood, nor have satisfactory methods been identified to date for its prediction, prevention and treatment. In order to minimize the potential impact of this syndrome on Space Shuttle crew operations the National Aeronautics and Space Administration has organized a broad program of inter-disciplinary research involving a large number of scientists in the United States. Current research on the etiology of space motion sickness is based to a large extent on the so called sensory conflict theory. Investigations of the behavioral and neurophysiological consequences of intralabyrinthine, as well as intermodality sensory conflict are being performed. The work in this area is being influenced by the presumed alterations that occur in otolith behavior in weightlessness. In addition to sensory conflict, the possible relationship between observed cephalad shifts of body fluids in weightlessness and space motion sickness is being investigated. Research to date has failed to support the fluid shift theory. Research underway to identify reliable test methods for the prediction of susceptibility to space motion sickness on an individual basis includes attempts to (a) correlate susceptibility in different provocative environments; (b) correlate susceptibility with vestibular and non-vestibular response parameters, the latter including behavioral, hemodynamic and biochemical factors and (c) correlate susceptibility with rate of acquisition and length of retention of sensory adaptation. Controlled studies are also being performed during parabolic flight as a means of attempting to validate predictive tests for susceptibility to this syndrome. Research to develop new or improved countermeasures for space motion sickness is underway in two primary areas. One of these involves anti-motion sickness drugs. Significant achievements have been realized with regard to the identification of new highly efficacious drug combinations, dose levels and routes of administration. Although pronounced individual variations must be accounted for in selecting the optimum drug and dose level, combinations of promethazine plus ephedrine or scopolamine plus dexidrine are presently the drugs of choice. Work is also underway to identify side effects associated with anti-motion sickness drug use and to identify new drugs which may selectively modify activity in central neural pathways involved in motion sickness. In addition to research on drugs, efforts are being made to develop practical vestibular training methods. Variables which influence rate of acquisition of adaptation, length of retention of adaptation and transfer of protective adaptation to new environments are being evaluated. Also, included in this area is the use of biofeedback and autogenic therapy to train individuals to regulate autonomic responses associated with motion sickness. While valuable new knowledge is expected to evolve from these combined research programs, it is concluded that the final validation of predictive tests and countermeasures will require a series of controlled space flight experiments.
Introduction CONCERNS t h a t a s t r o n a u t s m i g h t e x p e r i e n c e v e s t i b u l a r s y s t e m r e l a t e d d i s t u r bances, most noteably spatial disorientation and space motion sickness during or 1259
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following exposure to weightless space flight, have persisted throughout the history of the manned U.S. space program. These concerns, however, were not substantiated during the Mercury and Gemini programs where a total of 16 missions were flown with no reported incidents of disorientation or motion sickness by any of the 26 crewmen involved. As a precautionary measure, anti-motion sickness drugs were carried by these crewmen, but were never used. The course of events began to change with the Apollo Program. During this flight series a total of 11 incidents of inflight motion sickness, ranging from mild to severe were reported (Homick and Miller, 1975). Also, special tests conducted following the Apollo 16 mission revealed slight alterations in vestibular sensitivity and postural equilibrium during the immediate postflight period. It is generally believed that the increased opportunity for m o v e m e n t by the crewmen within the relatively large volume of the combined Apollo command and lunar modules was largely responsible for the high incidence of motion sickness reported. Such freedom of movement was not possible in the very confined crew compartments of the Mercury and Gemini spacecraft. The Skylab Program served to underscore the potential seriousness of space motion sickness as an operational problem for future manned spaceflight. Of the nine individuals who flew these missions, five experienced symptoms of motion sickness during the initial days of the flight. All of the reported incidents occurred during the second and third manned missions (Skylab 3 and 4). In two cases symptoms were severe and included vomiting. Anti-motion sickness drugs were used by the Skylab 3 and 4 crewmen, however, the drugs were not completely effective in ameliorating symptoms. R e c o v e r y was complete in 3-5 days for all of the crewmen affected. The time course, severity of symptoms experienced under operational conditions and the anti-motion sickness drugs used are summarized in Fig. 1. Opinions have varied regarding the overall impact MOTIONSICKNESSUNDEROPERATIONALCONDITIONS
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of the malaise experienced on the crewmens' ability to perform required mission tasks. Nevertheless, the more severely affected crewmen did find it necessary to restrict their physical activity to some extent during the first days of fight and it appeared that their general performance capability was temporarily degraded. In addition to the early inflight symptoms, motion sickness (sea sickness) was experienced by two of the Skylab 2 crewmen on the recovery ship during the first hours following splashdown. Anti-motion sickness drugs taken by all of the Skylab 3 and 4 crewmen immediately prior to reentry were generally successful in preventing or at minimizing the further occurrence of symptoms during the early postflight period. Aside from observations of operational or spontaneous motion sickness upon entry into weightlessness, a variety of pre-, in-, and postflight experimental test data were obtained on each of the Skylab crewmen. The majority of these were collected in conjunction with Skylab Experiment M131, Human Vestibular Function. Experiment M131 was comprised of three sub-experiments, namely, (1) susceptibility to motion sickness, (2) thresholds for perception of angular acceleration as indicated by the oculogyral illusion, and (3) perceived direction of internal and external space. Inflight assessments of susceptibility to experimentally induced motion sickness were conducted on or after mission day 8 by which time the crewmen had adapted to the weightless environment. Stressful Coriolis accelerations were provided by requiring the crewmen, with eyes covered, to execute standardized head movements while seated in a chair that could be rotated at velocities up to 30 rpm. The end point used was either a mild level of motion sickness or 150 discrete head movements. This experiment revealed that all of the crewmen tested were virtually symptom free even when exposed to the highest stress levels possible (150 head movements at 30rpm) with the experiment system used. Thus, following the initial period of adaptation, a marked decrease in susceptibility was observed inflight relative to each crewman's preflight baseline susceptibility. Susceptibility tests conducted postflight indicated a slight "refractoriness" during the immediate postflight period, the duration of which was related in a positive fashion to the length of zero-g exposure. That is, crewmen on the latter two missions, especially the 84-day Skylab 4 mission, displayed few if any symptoms initially postflight, but gradually (over a period of 5-30 days) returned to their preflight levels of susceptibility. These postflight observations were unrelated to anti-motion sickness drug use. Adaptive processes primarily involving otolith sensory inputs were believed to be largely responsible for the alterations in susceptibility to experimentally induced motion sickness observed inflight and postflight. Although some increased variability was noted in a few crewmen, thresholds for perception of the oculogyral illusion (OGI) were basically unchanged inflight relative to values obtained preflight. Likewise, no changes were observed immediately postflight with this measurement procedure. These findings provide evidence that semi-circular canal function is not altered in a zero-g field. However, the first OGI threshold tests were not conducted before mission day 5
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on any of the three missions. Therefore, whether or not canal sensitivity is modified during the first few days of weightless flight remains to be quantitatively determined. The third part of the Skylab M131 experiment which assessed perceived direction of internal and external space also failed to reveal any significant quantitative changes inflight or postflight. Nevertheless, a majority of the crewmen did report experiencing curious anomolies with visual spatial orientation. These episodes of spatial disorientation were always mild and transient, and typically occurred after transition to a location in the Skylab vehicle where a different visual frame of reference (i.e. local vertical) had to be assumed. The reader is invited to examine previously published reports for a thorough description and discussion of the Skylab M131 experiment results (Graybiel et al., 1975a; Graybiel et al., 1974). Several other types of pre- and postflight test data related to vestibular system function were obtained on the Skylab crewmen. Included preflight was an audiogram, a complete motion sickness history, a modified FitzgeraldHallpike test to assess canal function, measurements of ocular counterrolling to assess otolith function and measurements of postural equilibrium. The postural equilibrium test utilized narrow metal rails on which the crewmen were required to balance with eyes open, as well as eyes closed. This test was repeated on several occasions during the immediate postflight period. A comparison of the pre- and postflight data revealed a marked postflight deficit in postural equilibrium performance in the eyes closed test condition for all of the crewmen tested. Deficits with visual inputs were much less pronounced. Return to preflight postural performance occurred within 10 days. These findings were highly suggestive of functional alterations in proprioceptive, vestibular and neuromuscular sensory mechanisms induced by the prolonged absence of a normal gravitational stimulus (Homick and Reschke, 1977). The pre-, in- and postflight Skylab vestibular experiments briefly summarized above were necessarily limited in scope and yielded a relatively small amount of quantitative information. Virtually all of the data obtained from these experiments has been previously reported. No further attempts of any consequences have been made to re-evaluate those data. However, as stated previously, the unexpected frequency and severity of space motion sickness during the Skylab missions did result in an increase in concern about the possible consequences of this problem for future manned missions, particularly Space Shuttle crewmembers. Upon examining the operational requirements of the Shuttle Program the issue of space motion sickness assumes special significance for several reasons. First, all of the Shuttle flights will place high work load demands on the crewmembers and the flights will be relatively short (7-30 days) in duration. Therefore, crewmembers who are susceptible to space motion sickness could experience symptoms during a significant portion of the total mission duration. Secondly, the Shuttle orbiter and Spacelab will be sufficiently large in volume to permit extensive movement by the crewmembers. Past experience indicates that excessive movement during the first days of weightless flight is a significant factor in precipitating symptoms in susceptible individuals. Finally, a large
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number of individuals previously inexperienced with unusual gravito-inertial force environments, let alone weightless space flight, will be assigned as crewmembers. Again, past findings suggest that these persons may be more prone to develop vestibular related disturbances than astronauts with previous space flight experience (Homick and Miller, 1975). In an effort to minimize the potential deleterious impact of space motion sickness on the well-being and performance of Shuttle crewmembers, a broad program of research under the sponsorship of the National Aeronautics and Space Administration is underway in the United States. Four interrelated problem areas are being addressed by this program. These include research on the causes, prediction, prevention and treatment of space motion sickness. Each of these areas is briefly discussed below. Research strategies being used have been influenced to a large extent by information (both quantitative and qualitative) and insights gained from the Skylab Program. The results of most of the research in progress are preliminary and will not be presented here in detail. Current research programs: Rationale and preliminary findings Etiology Despite the considerable volume of research that has been documented on the subject, the causes of motion sickness, and in particular the form peculiar to zero-g space flight, are not well understood. Elucidation of the etiology of this syndrome is essential to the development of effective means for its prediction, prevention and treatment. Two theories on the etiology of space motion sickness are currently under investigation by NASA. One of these, which did not originate as a result of manned space flight, may be broadly encompassed by what has been previously described as the sensory conflict theory of motion sickness. The second theory, which has been named the fluid shift theory, received its impetus from the Skylab Program. This theory is based upon the observed redistribution of body fluids that occurs upon exposure to sustained zero-g. The sensory conflict and fluid shift theories of space motion sickness are not mutually exclusive. The sensory conflict theory as elaborated by Reason and Graybiel (1973) argues that motion sickness symptoms result from a mismatch between the total pattern of information from the spatial senses and that held in a neural store from previous experiences. The basic assumption is that motion sickness is a maladaptation phenomenon which occurs during the period of time that the contents of the neural store are at variance with the prevailing sensory influx. An essential proviso for this theory is the presence of an intact and functional vestibular system. Indeed, reports by astronauts indicate that the manifestation of symptoms is closely associated with head movements and concommitant vestibular stimulation. Restriction of head movements in zero-g has been one means of controlling symptom formation. In the context of the sensory conflict theory, a viewpoint widely held is that upon entry into zero-g, the otoliths play a primary role in supplying conflicting neural signals which mismatch signals from the semicircular canals, visual system, proprioceptors and related structures in the central nervous system.
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Considering the significance of the otoliths in the evolution of the species and the knowledge that the otoliths in a l-g environment depend upon a constant gravitational reference for proper function, it is quite conceivable that the otolith end organs upon exposure to zero-g may deliver unnatural inputs to a neural store in the central nervous system. The inability of the organism to initially resolve the resultant sensory conflict may be a major causal factor in the space motion sickness syndrome. A variety of interrelated neurophysiological, neuroanatomical, behavior and biochemical studies have been initiated since the end of the Skylab Program to examine various aspects of the sensory conflict theory. The results of most of these studies are preliminary, but do generally lend support to the notion of sensory conflict. No attempt is made here to summarize these studies. As stated above, the fluid shift theory of motion sickness is based largely on the observation of significant cephalad displacements of body fluid in astronauts during weightlessness. This phenomenon has been well documented (Thornton et al., 1974). Subjective reports by crewmen, as well as inflight photographs, indicate a distention of blood vessels in the neck and head, a puffy appearance of the cheeks and tissue surrounding the eyes, chronic nasal congestion and sensations of fullness of the head. Mild headache was also commonly reported. These findings suggest that increased intracranial fluid pressure or edema may be a causal factor in the space motion sickness syndrome. The majority of the research in this area to date has focused on the supposition that the observed fluid shifts result in an imbalance of labyrinthine fluid pressures which in turn alters neural activity in the vestibular pathways (possibly creating an intra or interlabyrinthine neural mismatch) and leads to the symptoms of motion sickness. Direct measurement of cerebral spinal fluid, and perilymph pressure in guinea pigs exposed to torso elevation and zero-g parabolic flight have failed to provide support for the fluid shift hypothesis of motion sickness (Parker, 1977). However, critical measurements of endolymph fluid pressure have yet to be made. Data obtained thus far with humans are also inconclusive. In one recent study it was found that there were no intra-individual differences in susceptibility to motion sickness resulting from rotation at 30 rpm in the earth horizontal, 10° head-up and 10° head-down positions (Graybiel and Lackner, 1977). In this study subjects assumed the test position 60min prior to testing, thus presumably allowing for some redistribution of body fluids. Responses suggestive of vestibular disturbances have been only occasionally reported by subjects exposed to fluid shifts induced by head-down tilt bedrest (Hyatt, Pers. Comm.). However, in these studies no purposeful effort was made to evaluate vestibular function by quantitative methods. A pilot study conducted at the Johnson Space Center to measure possible alterations in vestibular sensitivity by monitoring spontaneous and positional nystagmus during two hours of 10° head-down tilt yielded inconclusive results in the ten subjects tested (Homick and Reschke, unpubl'd). Despite the failure to date to clearly demonstrate a relationship between fluid shifts and motion sickness, this is an area which will continue to be investigated until it can be reasonably eliminated as a causal factor.
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Related indirectly to both of the above theories is a recent study which was designed to determine if processes underlying the neurosensory and neuromuscular functional alterations observed postflight in Skylab crewmen could be elucidated by using supine bedrest as an analog of weightlessness (Homick et al., 1976). In this study susceptibility to experimentally induced Coriolis motion sickness, postural equilibrium and vestibulospinal reflexes were measured in six male subjects before and immediately after 28 days of horizontal bedrest. Test methods employed were nearly identical to those used during the Skylab Program. On the basis of data obtained from this experiment it was concluded that with regard to sensory physiological processes, supine bedrest does not provide a valid analog of weightlessness of equivalent duration. The lack of any meaningful correlation between the bedrest study results and the Skylab postflight findings is not surprising if one considers the mechanisms thought to be responsible for the Skylab postflight changes. As already suggested it is most probable that, during the Skylab missions significant adaptive changes involving the otolith receptors occurred. Included, as a result of altered otolith activity, would have been modifications in the central nervous system processing of sensory information which were appropriate for the zero-g environment. Such modifications, however, were inappropriate for normal functioning in 1-g. Hence, upon return to l-g, the crewmen manifested response changes, most notably altered motion sickness susceptibility and postural instability, which gradually diminished and disappeared as they re-adapted to the 1-g environment. Such adaptive changes involving the otoliths and other gravi-receptors would not be expected in subjects undergoing supine bedrest in a l-g environment. Therefore, the lack of significant changes following bedrest should not be unexpected. Even if significant sensory physiological response changes did occur following bedrest of durations greater than 28-days, it is unlikely that the underlying causes would be the same as those associated with exposure to weightless space flight. The bedrest study briefly described above did not provide support for the fluid shift hypothesis of space motion sickness. It must be remembered, however, that in this study the subjects were bedrested in a horizontal position. Fluid shifts induced by prolonged head-down tilt bedrest could conceivably result in vestibular system related disturbances more like those seen during or following space flight. Such controlled observations have yet to be made. Not specifically related to either the sensory conflict or fluid shift theory, but still in the category of mechanisms underlying vestibular alterations in zero-g, were several inflight and postflight studies done with embryonic and young adult killifish (fundulus heteroclitus) during the Apollo-Soyuz Test Project (ASTP). These studies were designed to confirm and extend observations of embryonic development and vestibular adaptation made with killifish during the Skylab 3 flight. The results of these studies, which have been published elsewhere in detail, indicated subtle abnormalities in fish orientation behavior inflight, as well as postflight (Hoffman et al., 1977; Scheld et al., 1976). Adaptation was also observed. The embryos exhibited no gross abnormalities resulting from development in the zero-g environment.
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Prediction
The problem of selecting astronauts for space flight assignments from a motion sickness susceptibility point of view remains unresolved at this time. The Skylab experience did bring this problem into sharper focus. As already indicated, a variety of vestibulometric test data, as well as detailed motion sickness histories, were obtained from each of the Skylab astronauts during the period of time preceding their flights (Graybiel et al., 1975a; Graybiel et al., 1974). These tests indicated that all of these individuals possessed clinically normal vestibular function. None of these data, however, were predictive of the actual incidence of inflight motion sickness symptomatology. Indeed, several crewmen who demonstrated greater than average resistance to experimentally induced Coriolis motion sickness during the preflight tests experienced severe symptoms during the first few days of zero-g space flight. To date, analysis of specific pre-and inflight Skylab mission events, as well as analysis of physiological data obtained on the crewmen, have failed to yield meaningful clues in the search for reliable predictive tests. Because of its practical importance, efforts by NASA in this area are continuing. Several interrelated investigative approaches are being pursued. Laboratory tests are underway to determine the extent to which various provocative tests of motion sickness correlate with one another. Included in these studies are procedures designed to stress the canicular and otolith receptors independently and simultaneously. Also included are methods for producing disorientation and motion sickness which are primarily the result of sensory conflict, particularly visual-vestibular conflict. In addition to studies which correlate susceptibility to motion sickness caused by provocative methods, research is underway to evaluate the relationship between susceptibility and other reflex vestibular responses, as well as non-vestibular response parameters. Included among the non-vestibular responses are various psychodynamic, hemo-dynamic and biochemical factors which may be intrinsically related to susceptibility. Investigations involving these latter factors are, at present, highly preliminary in nature. The possibility that behavioral and/or physiological adaptability may be related to susceptibility is also being assessed. Studies in this area are based on the supposition that some individuals possess a propensity for rapid adaptation to stressful or novel environments while others are inherently slow adapters. Slow adapters may be less able to resolve sensory conflict that occurs upon entry into null gravity and, therefore, be more susceptible to disorientation and motion sickness symptomatology. Laboratory tests which reliably identify slow adapters or individuals unable to resolve sensory conflict, may be of value in discriminating persons susceptible to space motion sickness. An important element of this program is the use of NASA's KC-135 zero-g aircraft to evaluate the validity of various ground based tests for predicting susceptibility to motion sickness during the zero-g phase of parabolic flight. These studies are being conducted under the direction of Dr. Ashton Graybiei of the Naval Aerospace Medical Research Laboratory, Pensacola, Florida. A complex experimental protocol has been developed in which each subject's
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susceptibility is evaluated under conditions where visual cues and head movements are carefully controlled during the zero-g and hyper-g phases of parabolic flight. The results of the parabolic flight experiments are being compared with a variety of ground based vestibular test data obtained on the same individuals. If it can be demonstrated that certain laboratory tests are predictive of susceptibility to the zero-g phase of parabolic flight, then the validity of these same tests for predicting susceptibility to weightless space flight will be enhanced. With the exception of parabolic flight testing, none of the research strategies briefly outlined above are new in concept or unique to manned space flight. A considerable amount of research has been reported during the past two decades on attempts to develop predictive tests for susceptibility to motion sickness in seamen, and especially air crewmen. The results of these studies have often been inconclusive and conflicting. In general, they have failed to yield reliable predictors. The problem becomes even more difficult when considering space motion sickness because the underlying processes are not well understood and may differ, perhaps significantly, from motion sickness which occurs in a one-g field.
C ountermeasures
Methods used previously to prevent or treat space motion sickness have not been entirely satisfactory. As indicated by Fig. 1, combinations of scopolamine (0.35 mg) and dexidrine (5 rag) or promethazine (25 mg) and ephedrine (50 mg) were used by a majority of the Skylab crewmen during the first 1-3 days of flight. Based upon considerable laboratory research these drug combinations were believed to be the best available at the time. Also, during the preflight period, the efficacy of these drugs in significantly reducing susceptibility to Coriolis motion sickness was demonstrated for each crewman. Nevertheless, although these drugs helped to mitigate symptoms, they were not completely effective in preventing or treating inflight motion sickness. In judging the efficacy of these drugs it should be noted that in several cases they were not taken until after symptoms had clearly appeared. It is also noteworthy that prior to the Skylab missions, limited efforts were made by a number of the crewmen to acquire adaptation to stressful motion stimuli. These activities took two forms. In one case the crewmen executed head movements while rotating in the chair designed for the Skylab M131 vestibular function experiments. These "vestibular training" sessions, which generally involved the execution of 150-200 head movements at a chair velocity of 20 rpm, were performed with the aid of anti-motion sickness drugs. These sessions were in addition to the normally scheduled M131 experiment preflight baseline data collection tests. Only 2 or 3 of these vestibular training sessions were performed with each crewman. In addition to the rotating chair activities the crew of Skylab 4 flew aerobatic maneuvers in high performance jet aircraft approximately one hour per week during the 6-8 weeks preceding their flight. These aerobatic activities were not
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supervised by the M131 experiment investigators. However, they may have been effective in that a gradual decrease in susceptibility to Coriolis motion sickness was observed during the course of implementing the M131 preflight tests. The limited attempts by the Skylab crewmen to acquire adaptation preflight appear to have been of no consequence as evidenced by the high incidence of inflight motion sickness. Even in crewmen who did not experience symptoms the value of preflight adaptation training was clouded because of the inflight use of anti-motion sickness drugs. A need to develop more effective countermeasures for space motion sickness clearly exists if future astronauts are to be spared the discomfort, inconvience and possible performance decrement caused by this syndrome. Current research efforts in this area are focusing on the development of new or improved pharmacological, as well as non-pharmacological countermeasures. Much of the new knowledge that has developed in this area since the Skylab Program, particularly that on anti-motion sickness drugs, has been contributed by Dr. Ashton Graybiel and his colleagues. Studies utilizing the Slow Rotating Room (SRR) at Pensacola revealed that a fixed dose combination of promethazine (25 mg) and ephedrine (25mg) provided outstanding protection against motion sickness (Graybiel et al., 1975b). This combination was as effective as the combination of scopolamine and dexidrine which had been established in previous studies as the best drug for preventing and treating motion sickness. The relative benefits of the promethazine plus ephedrine combination have been substantiated in more recent studies (Johnson et al., 1975; Graybiel and Knepton, 1977). These findings, combined with the knowledge that promethazine plus ephedrine provides longer lasting protection and appears to produce fewer side effects, makes this combination the drug of choice at the present time. Preliminary results from drug studies conducted during parabolic flight support this conclusion (Graybiel, pers. comm.). The Pensacola Slow Rotating Room and parabolic flight drug studies have also revealed great individual differences in response to anti-motion sickness drugs, implying that individual assessments must be made for maximal benefits. This finding assumes significance with regard to the expense and time that may become involved with selecting the optimum drug for individual flight crewmembers. The vast majority of drug studies to date have investigated the efficacy of drugs taken by mouth. As evidenced by the Skylab experience, drugs taken orally may be of little value if one is already manifesting symptoms. To deal with this problem research is underway to evaluate the efficacy of drugs administered by other routes. Scopolomine absorbed through the skin has been demonstrated to be a promising method for the long term control of motion sickness (Graybiel et al., 1976). Also, intra-muscular injections of promethazine and scopolomine given to subjects experiencing severe and acute motion sickness during parabolic flight have been very effective in alleviating symptoms (Graybiel, pers. comm.) Prominent side effects, noteably drowsiness, may occur with this type of treatment. Efforts are being made to better understand the behavioral and physiological side effects of various anti-motion sickness drugs.
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The majority of anti-motion sickness drug research conducted since the Skylab Program has emphasized the evaluation of drugs previously known to have anti-motion sickness properties. While the drugs now identified may prove, as a result of further research, to be the drugs of choice in the future, pilot studies are underway to identify new effective drugs. Some of these studies seek to isolate drugs which may modify neural and/or biochemical processes in specific areas of the central nervous system. This approach requires knowledge of the etiology of motion sickness, the pathways involved and how drugs might selectively effect activity in those pathways. In short, this approach deals with the site of drug action and is intended to control the causes of space motion sickness as opposed to merely suppressing symptoms. The development of a suitable animal model for space sickness will be important to the progress that can be made on such site of action drug studies. Two non-pharmacological countermeasures for space motion sickness are under investigation. The foremost of these involves investigations of neurosensory, especially vestibular system, adaptation processes. From these studies it is hoped that effective ground based laboratory techniques can be developed for imparting protective preflight adaptation to future astronauts. Past studies have demonstrated that vestibular adaptation can be acquired. However, the major question under investigation is whether or not such adaptation transfers in a positive fashion to the zero-g environment. To this end a variety of studies are being performed to evaluate such factors as rate of acquisition of adaptation, rate of decay of adaptation and most importantly, the degree to which adaptation acquired in one motion environment transfers to another motion environment. Many of these studies are being carried out with the Pensacola Slow Rotating Room. Also, in order to evaluate transfer effects which more closely approximate the transition to weightless spaceflight, parabolic flight will be utilized. In these planned studies, subjects who are susceptible to motion sickness induced by head movements during the zero-g phase of parabolic flight will be exposed to special vestibular adaptation training protocols and then be re-tested under the same provocative parabolic flight conditions. In addition to vestibular adaptation training a new approach is being applied to the development of an effective countermeasure for motion sickness. Investigators at the NASA-Ames Research Center are using bio-feedback and autogenic therapy to train subjects to control autonomic nervous system responses of the type associated with motion sickness. This is a novel approach which has met with varied success when used in other applications. Nevertheless, preliminary findings have been encouraging and research with this method will continue. Summary and conclusions The unexpectedly high incidence of space motion sickness experienced by the Skylab astronauts indicates convincingly that this syndrome represents a potential threat to the well-being and operational efficiency of at least some individuals who will fly future space missions. Effective means for dealing with this syndrome have proven to be elusive. Although generally considered to be a
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maladaptation phenomenon which occurs upon initial exposure to the novel weightless state, the specific mechanisms underlying space motion sickness are not well understood at this time. Just as importantly from a practical point of view, reliable methods for the a priori identification of individuals susceptible to this syndrome are presently lacking. Also, effective and operationally acceptable methods for preventing and treating symptomatology are not entirely adequate. In an effort to resolve these issues, NASA has undertaken a broad, interdisciplinary program of research. A large number of vestibular investigators at various government and university laboratories in the U.S. are applying their knowledge to this program. The majority of research in progress to define the etiology of space motion sickness is generally based on the premise that the syndrome is the overt manifestation of unresolved sensory conflict. In all likelihood, modifications in otolith behavior which occur during the first few hours in weightlessness are a primary factor in creating sensory conflict. The conflict may be in part intralabyrinthine in origin. That is, the normal synergy that is thought to exist between the semicircular canals and otoliths may be disrupted, thus resulting in modified neural outflow. Also, it is probable that intermodality conflict involving the visual, vestibular and the touch, pressure and kinesthetic senses occurs. The net result may be an inability of the central nervous system to properly integrate the mismatched sensory influx. Adaptive processes in the central nervous system presumably occur as evidenced by the gradual and complete recovery from symptoms of motion sickness. Extensive research, much of it involving the use of various electro-physiological, neuroanatomical, behavior and biochemical methodologies, is being directed toward the investigation of the sensory conflict theory. Aside from sensory conflict the Skylab program gave impetus to research on a new theory of space motion sickness, namely the fluid shift theory. This theory has its primary origin in the distinct observations of cephalad shifts of body fluids in weightlessness. It has been postulated that these fluid shifts may alter vestibular function as a result of creating subtle pressure changes in the labyrinthine fluids. Others have speculated that brain biochemical alterations may result from intracranial edema. Research to date with humans and animals has failed to support the fluid shift theory. Nevertheless, this theory warrants attention and will continue to be scrutinized. Of the various unresolved issues related to space motion sickness, the one which is most perplexing involves the development of predictors of susceptibility. The issue appears not to be one of simply making gross distinctions between high, moderate and low susceptibility to experimentally induced motion sickness. As previously indicated, all of the Skylab crewmen demonstrated moderate to low susceptibility during ground based tests, yet many of these individuals experienced inflight symptomatology. Most past research in this area has yielded results of limited usefulness. Clearly, new approaches are required. It would seem that emphasis should be placed on research wherein motion sickness is provoked largely by otolith stimulation and by exposure to conditions which evoke sensory conflict. That is, provocative and nonprovocative stimuli
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which attempt to activate those mechanisms thought to underly space motion sickness may prove to be a fruitful approach to the definition of valid predictive tests. Another promising approach involves determinations of rate of adaptation. Individuals who possess a propensity for rapid adaption to novel or stressful environments may experience fewer and shorter lived disturbances upon entry into zero-gravity. Also, other variables including predisposing psychodymic traits and intrinsic biochemical factors should and are being explored. The judicious use of parabolic flight is included among the resources that are being utilized in the implementation of these studies. Despite the insights that hopefully will be gained as a result of these ground based studies, it is anticipated that the final validation of predictive tests will require a series of controlled experiments with individuals who have flown previously in space, and more importantly, with those who will fly on the Space Shuttle missions. Modest progress has been made since the termination of the Skylab program in the identification of more effective pharmacological counter-measures for space motion sickness. On the basis of a series of studies using the Pensacola Slow Rotating Room and parabolic fight it has been demonstrated that the drug combination of promethazine and ephedrine (25 mg each) is a highly effective antimotion sickness drug for a substantial number of individuals. This combination has proven to be as efficacious as the long standing scopolomine and dexedrine combination, and typically produces fewer side effects. Advances have also been made in the development and testing of non-oral methods of drug administration. A small adhesive disc which permits the slow absorbtion of scopolomine through the skin has been successfully tested as a method of long term drug administration. More significant has been the treatment of severe and acute motion sickness by intramuscular injections of promethazine and scopolomine. Despite their usefulness, anti-motion sickness drugs may exact penalties in the form of detrimental side effects. Therefore, research is continuing to examine more thoroughly the behavioral and physiological consequences of using drugs as a countermeasure. In addition to the identification of new or improved drugs, the development of practical vestibular adaptation training methods continues to be of great significance. In this area efforts are being made to acquire more information related to the acquisition, retention and transfer of adaptation. Of paramount importance is whether or not adaptation acquired by whatever means preflight transfers in a beneficial manner to the space flight environment. Again, the Pensacola Slow Rotating Room and the parabolic flight aircraft have proven to be valuable research tools in the investigation of adaptation effects. Other research on non-pharmacological approaches to the development of counter measures currently includes the use of biofeedback training and autogenic therapy. Which of the countermeasures under investigation will be the most practical remains to be determined. Pharmacological methods are relatively easy to implement, especially inflight, and should involve a minimum of crew time. Such methods have the disadvantage, however, of creating potentially unacceptable side effects for some individuals, especially with prolonged drug use. Training
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methods avoid the problems associated with drugs, but may demand a considera b l e a m o u n t o f p r e f l i g h t c r e w t i m e . A s w i t h p r e d i c t i v e t e s t s , t h e final v a l i d a t i o n of countermeasures for space motion sickness, especially those employing t r a i n i n g t e c h n i q u e s , will r e q u i r e a s e r i e s o f c o n t r o l l e d s t u d i e s w i t h i n d i v i d u a l s w h o fly o n t h e S p a c e S h u t t l e m i s s i o n s . References Graybiel A. Personal communication. Graybiel A. and Lackner J. R. (1977) Comparison of susceptibility to motion sickness during rotation at 30rpm in the earth-horizontal, 10° head-up and 10° head-down positions. Avait. Space Environ. Med. 48(1), 7-11. Graybiel A. and Knepton J. (1977) Evaluation of a new antinauseant drug for the prevention of motion sickness. Aeait. Space Environ. Med. 48(9), 867-871. Graybiel A., Knepton J. and Shaw J. (1976) Prevention of experimental motion sickness by scopolamine absorbed through the skin. Avait. Space Environ. Med. 47(10), 1096-1100. Graybiel A., Miller E. F. II and Homick J. L. (1974) Experiment Mi31: Human vestibular function. In Proc. of the Skylab Life Sciences Syrup. Vol. 1, pp. 169-220. NASA TMX-58154. Graybiel A., Miller E. F. II and Homick J. L. (1975a) Individual differences in susceptibility to motion sickness among six Skylab astronauts. Acta Astronautica 2, 155-174 Graybiel A., Wood C. D., Knepton J., Hoche J. P. and Perkins G. F. (1975b) Human assay of anti-motion sickness drugs. Avait. Space Environ. Med. 46(9), 1107-1118. Hoffman R. B., Salinas G. A. and Baky A. A. (1977) Behavioral Analysis of killifish exposed to weightlessness in the Apollo-Soyuz Test Project. Avait. Space Environ. Med. 48(8), 712-717. Homick J. L. and Miller E. F. (1975) Apollo flight crew vestibular assessment. In Biomedical Results of Apollo, pp. 323-368. NASA SP-368. Homick J. L. and Reschke M. F. Unpublished data. Homick J. L. and Reschke M. F. (1977) Postural equilibrium following exposure to weightless space flight. Acta Otolaryngol 83, 455-464. Homick J. L., Reschke M. F., Moore M. J. and Anderson D. J. (1976) The effect of 28-days supine bedrest on vestibular system function. In Report of 28-day Bedrest Simulation of Skylab. Contract NAS9-14578, December. Hyatt K. H. Personal communication. Johnson W. H., Money K. E. and Graybiel A. (1976) Airborne testing of three anti-motion sickness preparations. Avait. Space Environ. Med. 47(11), 1214--1216. Parker D. E. (1977) Labyrinth and cerebral-spinal fluid pressure changes in guinea pigs and monkeys during simulated zero-g. Avait. Space Environ. Med. 48(4), 356-361 (1977). Reason J. and Graybiel A. (1973) Factors contributing to motion sickness susceptibility: adaptability and receptivity. In AGARD Conference on Predictability of Motion Sickness in the Selection of Pilots. AGARD-CP-109. Scheld H. W. et al. (1976) Killifish hatching and orientation, experiment MA-161. In Apollo-Soyuz Test Project Preliminary Science Report. NASA TMX-58173. Thornton W. E., Hoffler G. W. and Rummel J. A. (1974) Anthropometric changes and fluid shifts. In Proc. of the Skylab Life Sciences Syrup. pp. 637-658. NASA TMX-58154.
Space motion sickness J. L. H O M I C K Medical Sciences Division, NASA-Johnson Space Center, Houston, TX 77058, U.S.A.
(Received 10 January 1978) Abstract--Space motion sickness, presumably triggered by sudden entry into a weightless environment, occurred with unexpected frequency and severity among astronauts who flew the Skylab missions. Recovery from symptoms was complete within 3-5 days, and as revealed by the Skylab MI31 Human Vestibular Function Experiment, all crewmembers were immune to experimentally induced motion sickness after mission day 8. This syndrome has been recognized as a possible threat to the early mission well-being and operational efficiency of at least some individuals who will fly space missions in the future. The causes of space motion sickness are not clearly understood, nor have satisfactory methods been identified to date for its prediction, prevention and treatment. In order to minimize the potential impact of this syndrome on Space Shuttle crew operations the National Aeronautics and Space Administration has organized a broad program of inter-disciplinary research involving a large number of scientists in the United States. Current research on the etiology of space motion sickness is based to a large extent on the so called sensory conflict theory. Investigations of the behavioral and neurophysiological consequences of intralabyrinthine, as well as intermodality sensory conflict are being performed. The work in this area is being influenced by the presumed alterations that occur in otolith behavior in weightlessness. In addition to sensory conflict, the possible relationship between observed cephalad shifts of body fluids in weightlessness and space motion sickness is being investigated. Research to date has failed to support the fluid shift theory. Research underway to identify reliable test methods for the prediction of susceptibility to space motion sickness on an individual basis includes attempts to (a) correlate susceptibility in different provocative environments; (b) correlate susceptibility with vestibular and non-vestibular response parameters, the latter including behavioral, hemodynamic and biochemical factors and (c) correlate susceptibility with rate of acquisition and length of retention of sensory adaptation. Controlled studies are also being performed during parabolic flight as a means of attempting to validate predictive tests for susceptibility to this syndrome. Research to develop new or improved countermeasures for space motion sickness is underway in two primary areas. One of these involves anti-motion sickness drugs. Significant achievements have been realized with regard to the identification of new highly efficacious drug combinations, dose levels and routes of administration. Although pronounced individual variations must be accounted for in selecting the optimum drug and dose level, combinations of promethazine plus ephedrine or scopolamine plus dexidrine are presently the drugs of choice. Work is also underway to identify side effects associated with anti-motion sickness drug use and to identify new drugs which may selectively modify activity in central neural pathways involved in motion sickness. In addition to research on drugs, efforts are being made to develop practical vestibular training methods. Variables which influence rate of acquisition of adaptation, length of retention of adaptation and transfer of protective adaptation to new environments are being evaluated. Also, included in this area is the use of biofeedback and autogenic therapy to train individuals to regulate autonomic responses associated with motion sickness. While valuable new knowledge is expected to evolve from these combined research programs, it is concluded that the final validation of predictive tests and countermeasures will require a series of controlled space flight experiments.
Introduction CONCERNS t h a t a s t r o n a u t s m i g h t e x p e r i e n c e v e s t i b u l a r s y s t e m r e l a t e d d i s t u r bances, most noteably spatial disorientation and space motion sickness during or 1259
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following exposure to weightless space flight, have persisted throughout the history of the manned U.S. space program. These concerns, however, were not substantiated during the Mercury and Gemini programs where a total of 16 missions were flown with no reported incidents of disorientation or motion sickness by any of the 26 crewmen involved. As a precautionary measure, anti-motion sickness drugs were carried by these crewmen, but were never used. The course of events began to change with the Apollo Program. During this flight series a total of 11 incidents of inflight motion sickness, ranging from mild to severe were reported (Homick and Miller, 1975). Also, special tests conducted following the Apollo 16 mission revealed slight alterations in vestibular sensitivity and postural equilibrium during the immediate postflight period. It is generally believed that the increased opportunity for m o v e m e n t by the crewmen within the relatively large volume of the combined Apollo command and lunar modules was largely responsible for the high incidence of motion sickness reported. Such freedom of movement was not possible in the very confined crew compartments of the Mercury and Gemini spacecraft. The Skylab Program served to underscore the potential seriousness of space motion sickness as an operational problem for future manned spaceflight. Of the nine individuals who flew these missions, five experienced symptoms of motion sickness during the initial days of the flight. All of the reported incidents occurred during the second and third manned missions (Skylab 3 and 4). In two cases symptoms were severe and included vomiting. Anti-motion sickness drugs were used by the Skylab 3 and 4 crewmen, however, the drugs were not completely effective in ameliorating symptoms. R e c o v e r y was complete in 3-5 days for all of the crewmen affected. The time course, severity of symptoms experienced under operational conditions and the anti-motion sickness drugs used are summarized in Fig. 1. Opinions have varied regarding the overall impact MOTIONSICKNESSUNDEROPERATIONALCONDITIONS
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of the malaise experienced on the crewmens' ability to perform required mission tasks. Nevertheless, the more severely affected crewmen did find it necessary to restrict their physical activity to some extent during the first days of fight and it appeared that their general performance capability was temporarily degraded. In addition to the early inflight symptoms, motion sickness (sea sickness) was experienced by two of the Skylab 2 crewmen on the recovery ship during the first hours following splashdown. Anti-motion sickness drugs taken by all of the Skylab 3 and 4 crewmen immediately prior to reentry were generally successful in preventing or at minimizing the further occurrence of symptoms during the early postflight period. Aside from observations of operational or spontaneous motion sickness upon entry into weightlessness, a variety of pre-, in-, and postflight experimental test data were obtained on each of the Skylab crewmen. The majority of these were collected in conjunction with Skylab Experiment M131, Human Vestibular Function. Experiment M131 was comprised of three sub-experiments, namely, (1) susceptibility to motion sickness, (2) thresholds for perception of angular acceleration as indicated by the oculogyral illusion, and (3) perceived direction of internal and external space. Inflight assessments of susceptibility to experimentally induced motion sickness were conducted on or after mission day 8 by which time the crewmen had adapted to the weightless environment. Stressful Coriolis accelerations were provided by requiring the crewmen, with eyes covered, to execute standardized head movements while seated in a chair that could be rotated at velocities up to 30 rpm. The end point used was either a mild level of motion sickness or 150 discrete head movements. This experiment revealed that all of the crewmen tested were virtually symptom free even when exposed to the highest stress levels possible (150 head movements at 30rpm) with the experiment system used. Thus, following the initial period of adaptation, a marked decrease in susceptibility was observed inflight relative to each crewman's preflight baseline susceptibility. Susceptibility tests conducted postflight indicated a slight "refractoriness" during the immediate postflight period, the duration of which was related in a positive fashion to the length of zero-g exposure. That is, crewmen on the latter two missions, especially the 84-day Skylab 4 mission, displayed few if any symptoms initially postflight, but gradually (over a period of 5-30 days) returned to their preflight levels of susceptibility. These postflight observations were unrelated to anti-motion sickness drug use. Adaptive processes primarily involving otolith sensory inputs were believed to be largely responsible for the alterations in susceptibility to experimentally induced motion sickness observed inflight and postflight. Although some increased variability was noted in a few crewmen, thresholds for perception of the oculogyral illusion (OGI) were basically unchanged inflight relative to values obtained preflight. Likewise, no changes were observed immediately postflight with this measurement procedure. These findings provide evidence that semi-circular canal function is not altered in a zero-g field. However, the first OGI threshold tests were not conducted before mission day 5
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on any of the three missions. Therefore, whether or not canal sensitivity is modified during the first few days of weightless flight remains to be quantitatively determined. The third part of the Skylab M131 experiment which assessed perceived direction of internal and external space also failed to reveal any significant quantitative changes inflight or postflight. Nevertheless, a majority of the crewmen did report experiencing curious anomolies with visual spatial orientation. These episodes of spatial disorientation were always mild and transient, and typically occurred after transition to a location in the Skylab vehicle where a different visual frame of reference (i.e. local vertical) had to be assumed. The reader is invited to examine previously published reports for a thorough description and discussion of the Skylab M131 experiment results (Graybiel et al., 1975a; Graybiel et al., 1974). Several other types of pre- and postflight test data related to vestibular system function were obtained on the Skylab crewmen. Included preflight was an audiogram, a complete motion sickness history, a modified FitzgeraldHallpike test to assess canal function, measurements of ocular counterrolling to assess otolith function and measurements of postural equilibrium. The postural equilibrium test utilized narrow metal rails on which the crewmen were required to balance with eyes open, as well as eyes closed. This test was repeated on several occasions during the immediate postflight period. A comparison of the pre- and postflight data revealed a marked postflight deficit in postural equilibrium performance in the eyes closed test condition for all of the crewmen tested. Deficits with visual inputs were much less pronounced. Return to preflight postural performance occurred within 10 days. These findings were highly suggestive of functional alterations in proprioceptive, vestibular and neuromuscular sensory mechanisms induced by the prolonged absence of a normal gravitational stimulus (Homick and Reschke, 1977). The pre-, in- and postflight Skylab vestibular experiments briefly summarized above were necessarily limited in scope and yielded a relatively small amount of quantitative information. Virtually all of the data obtained from these experiments has been previously reported. No further attempts of any consequences have been made to re-evaluate those data. However, as stated previously, the unexpected frequency and severity of space motion sickness during the Skylab missions did result in an increase in concern about the possible consequences of this problem for future manned missions, particularly Space Shuttle crewmembers. Upon examining the operational requirements of the Shuttle Program the issue of space motion sickness assumes special significance for several reasons. First, all of the Shuttle flights will place high work load demands on the crewmembers and the flights will be relatively short (7-30 days) in duration. Therefore, crewmembers who are susceptible to space motion sickness could experience symptoms during a significant portion of the total mission duration. Secondly, the Shuttle orbiter and Spacelab will be sufficiently large in volume to permit extensive movement by the crewmembers. Past experience indicates that excessive movement during the first days of weightless flight is a significant factor in precipitating symptoms in susceptible individuals. Finally, a large
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number of individuals previously inexperienced with unusual gravito-inertial force environments, let alone weightless space flight, will be assigned as crewmembers. Again, past findings suggest that these persons may be more prone to develop vestibular related disturbances than astronauts with previous space flight experience (Homick and Miller, 1975). In an effort to minimize the potential deleterious impact of space motion sickness on the well-being and performance of Shuttle crewmembers, a broad program of research under the sponsorship of the National Aeronautics and Space Administration is underway in the United States. Four interrelated problem areas are being addressed by this program. These include research on the causes, prediction, prevention and treatment of space motion sickness. Each of these areas is briefly discussed below. Research strategies being used have been influenced to a large extent by information (both quantitative and qualitative) and insights gained from the Skylab Program. The results of most of the research in progress are preliminary and will not be presented here in detail. Current research programs: Rationale and preliminary findings Etiology Despite the considerable volume of research that has been documented on the subject, the causes of motion sickness, and in particular the form peculiar to zero-g space flight, are not well understood. Elucidation of the etiology of this syndrome is essential to the development of effective means for its prediction, prevention and treatment. Two theories on the etiology of space motion sickness are currently under investigation by NASA. One of these, which did not originate as a result of manned space flight, may be broadly encompassed by what has been previously described as the sensory conflict theory of motion sickness. The second theory, which has been named the fluid shift theory, received its impetus from the Skylab Program. This theory is based upon the observed redistribution of body fluids that occurs upon exposure to sustained zero-g. The sensory conflict and fluid shift theories of space motion sickness are not mutually exclusive. The sensory conflict theory as elaborated by Reason and Graybiel (1973) argues that motion sickness symptoms result from a mismatch between the total pattern of information from the spatial senses and that held in a neural store from previous experiences. The basic assumption is that motion sickness is a maladaptation phenomenon which occurs during the period of time that the contents of the neural store are at variance with the prevailing sensory influx. An essential proviso for this theory is the presence of an intact and functional vestibular system. Indeed, reports by astronauts indicate that the manifestation of symptoms is closely associated with head movements and concommitant vestibular stimulation. Restriction of head movements in zero-g has been one means of controlling symptom formation. In the context of the sensory conflict theory, a viewpoint widely held is that upon entry into zero-g, the otoliths play a primary role in supplying conflicting neural signals which mismatch signals from the semicircular canals, visual system, proprioceptors and related structures in the central nervous system.
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Considering the significance of the otoliths in the evolution of the species and the knowledge that the otoliths in a l-g environment depend upon a constant gravitational reference for proper function, it is quite conceivable that the otolith end organs upon exposure to zero-g may deliver unnatural inputs to a neural store in the central nervous system. The inability of the organism to initially resolve the resultant sensory conflict may be a major causal factor in the space motion sickness syndrome. A variety of interrelated neurophysiological, neuroanatomical, behavior and biochemical studies have been initiated since the end of the Skylab Program to examine various aspects of the sensory conflict theory. The results of most of these studies are preliminary, but do generally lend support to the notion of sensory conflict. No attempt is made here to summarize these studies. As stated above, the fluid shift theory of motion sickness is based largely on the observation of significant cephalad displacements of body fluid in astronauts during weightlessness. This phenomenon has been well documented (Thornton et al., 1974). Subjective reports by crewmen, as well as inflight photographs, indicate a distention of blood vessels in the neck and head, a puffy appearance of the cheeks and tissue surrounding the eyes, chronic nasal congestion and sensations of fullness of the head. Mild headache was also commonly reported. These findings suggest that increased intracranial fluid pressure or edema may be a causal factor in the space motion sickness syndrome. The majority of the research in this area to date has focused on the supposition that the observed fluid shifts result in an imbalance of labyrinthine fluid pressures which in turn alters neural activity in the vestibular pathways (possibly creating an intra or interlabyrinthine neural mismatch) and leads to the symptoms of motion sickness. Direct measurement of cerebral spinal fluid, and perilymph pressure in guinea pigs exposed to torso elevation and zero-g parabolic flight have failed to provide support for the fluid shift hypothesis of motion sickness (Parker, 1977). However, critical measurements of endolymph fluid pressure have yet to be made. Data obtained thus far with humans are also inconclusive. In one recent study it was found that there were no intra-individual differences in susceptibility to motion sickness resulting from rotation at 30 rpm in the earth horizontal, 10° head-up and 10° head-down positions (Graybiel and Lackner, 1977). In this study subjects assumed the test position 60min prior to testing, thus presumably allowing for some redistribution of body fluids. Responses suggestive of vestibular disturbances have been only occasionally reported by subjects exposed to fluid shifts induced by head-down tilt bedrest (Hyatt, Pers. Comm.). However, in these studies no purposeful effort was made to evaluate vestibular function by quantitative methods. A pilot study conducted at the Johnson Space Center to measure possible alterations in vestibular sensitivity by monitoring spontaneous and positional nystagmus during two hours of 10° head-down tilt yielded inconclusive results in the ten subjects tested (Homick and Reschke, unpubl'd). Despite the failure to date to clearly demonstrate a relationship between fluid shifts and motion sickness, this is an area which will continue to be investigated until it can be reasonably eliminated as a causal factor.
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Related indirectly to both of the above theories is a recent study which was designed to determine if processes underlying the neurosensory and neuromuscular functional alterations observed postflight in Skylab crewmen could be elucidated by using supine bedrest as an analog of weightlessness (Homick et al., 1976). In this study susceptibility to experimentally induced Coriolis motion sickness, postural equilibrium and vestibulospinal reflexes were measured in six male subjects before and immediately after 28 days of horizontal bedrest. Test methods employed were nearly identical to those used during the Skylab Program. On the basis of data obtained from this experiment it was concluded that with regard to sensory physiological processes, supine bedrest does not provide a valid analog of weightlessness of equivalent duration. The lack of any meaningful correlation between the bedrest study results and the Skylab postflight findings is not surprising if one considers the mechanisms thought to be responsible for the Skylab postflight changes. As already suggested it is most probable that, during the Skylab missions significant adaptive changes involving the otolith receptors occurred. Included, as a result of altered otolith activity, would have been modifications in the central nervous system processing of sensory information which were appropriate for the zero-g environment. Such modifications, however, were inappropriate for normal functioning in 1-g. Hence, upon return to l-g, the crewmen manifested response changes, most notably altered motion sickness susceptibility and postural instability, which gradually diminished and disappeared as they re-adapted to the 1-g environment. Such adaptive changes involving the otoliths and other gravi-receptors would not be expected in subjects undergoing supine bedrest in a l-g environment. Therefore, the lack of significant changes following bedrest should not be unexpected. Even if significant sensory physiological response changes did occur following bedrest of durations greater than 28-days, it is unlikely that the underlying causes would be the same as those associated with exposure to weightless space flight. The bedrest study briefly described above did not provide support for the fluid shift hypothesis of space motion sickness. It must be remembered, however, that in this study the subjects were bedrested in a horizontal position. Fluid shifts induced by prolonged head-down tilt bedrest could conceivably result in vestibular system related disturbances more like those seen during or following space flight. Such controlled observations have yet to be made. Not specifically related to either the sensory conflict or fluid shift theory, but still in the category of mechanisms underlying vestibular alterations in zero-g, were several inflight and postflight studies done with embryonic and young adult killifish (fundulus heteroclitus) during the Apollo-Soyuz Test Project (ASTP). These studies were designed to confirm and extend observations of embryonic development and vestibular adaptation made with killifish during the Skylab 3 flight. The results of these studies, which have been published elsewhere in detail, indicated subtle abnormalities in fish orientation behavior inflight, as well as postflight (Hoffman et al., 1977; Scheld et al., 1976). Adaptation was also observed. The embryos exhibited no gross abnormalities resulting from development in the zero-g environment.
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Prediction
The problem of selecting astronauts for space flight assignments from a motion sickness susceptibility point of view remains unresolved at this time. The Skylab experience did bring this problem into sharper focus. As already indicated, a variety of vestibulometric test data, as well as detailed motion sickness histories, were obtained from each of the Skylab astronauts during the period of time preceding their flights (Graybiel et al., 1975a; Graybiel et al., 1974). These tests indicated that all of these individuals possessed clinically normal vestibular function. None of these data, however, were predictive of the actual incidence of inflight motion sickness symptomatology. Indeed, several crewmen who demonstrated greater than average resistance to experimentally induced Coriolis motion sickness during the preflight tests experienced severe symptoms during the first few days of zero-g space flight. To date, analysis of specific pre-and inflight Skylab mission events, as well as analysis of physiological data obtained on the crewmen, have failed to yield meaningful clues in the search for reliable predictive tests. Because of its practical importance, efforts by NASA in this area are continuing. Several interrelated investigative approaches are being pursued. Laboratory tests are underway to determine the extent to which various provocative tests of motion sickness correlate with one another. Included in these studies are procedures designed to stress the canicular and otolith receptors independently and simultaneously. Also included are methods for producing disorientation and motion sickness which are primarily the result of sensory conflict, particularly visual-vestibular conflict. In addition to studies which correlate susceptibility to motion sickness caused by provocative methods, research is underway to evaluate the relationship between susceptibility and other reflex vestibular responses, as well as non-vestibular response parameters. Included among the non-vestibular responses are various psychodynamic, hemo-dynamic and biochemical factors which may be intrinsically related to susceptibility. Investigations involving these latter factors are, at present, highly preliminary in nature. The possibility that behavioral and/or physiological adaptability may be related to susceptibility is also being assessed. Studies in this area are based on the supposition that some individuals possess a propensity for rapid adaptation to stressful or novel environments while others are inherently slow adapters. Slow adapters may be less able to resolve sensory conflict that occurs upon entry into null gravity and, therefore, be more susceptible to disorientation and motion sickness symptomatology. Laboratory tests which reliably identify slow adapters or individuals unable to resolve sensory conflict, may be of value in discriminating persons susceptible to space motion sickness. An important element of this program is the use of NASA's KC-135 zero-g aircraft to evaluate the validity of various ground based tests for predicting susceptibility to motion sickness during the zero-g phase of parabolic flight. These studies are being conducted under the direction of Dr. Ashton Graybiei of the Naval Aerospace Medical Research Laboratory, Pensacola, Florida. A complex experimental protocol has been developed in which each subject's
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susceptibility is evaluated under conditions where visual cues and head movements are carefully controlled during the zero-g and hyper-g phases of parabolic flight. The results of the parabolic flight experiments are being compared with a variety of ground based vestibular test data obtained on the same individuals. If it can be demonstrated that certain laboratory tests are predictive of susceptibility to the zero-g phase of parabolic flight, then the validity of these same tests for predicting susceptibility to weightless space flight will be enhanced. With the exception of parabolic flight testing, none of the research strategies briefly outlined above are new in concept or unique to manned space flight. A considerable amount of research has been reported during the past two decades on attempts to develop predictive tests for susceptibility to motion sickness in seamen, and especially air crewmen. The results of these studies have often been inconclusive and conflicting. In general, they have failed to yield reliable predictors. The problem becomes even more difficult when considering space motion sickness because the underlying processes are not well understood and may differ, perhaps significantly, from motion sickness which occurs in a one-g field.
C ountermeasures
Methods used previously to prevent or treat space motion sickness have not been entirely satisfactory. As indicated by Fig. 1, combinations of scopolamine (0.35 mg) and dexidrine (5 rag) or promethazine (25 mg) and ephedrine (50 mg) were used by a majority of the Skylab crewmen during the first 1-3 days of flight. Based upon considerable laboratory research these drug combinations were believed to be the best available at the time. Also, during the preflight period, the efficacy of these drugs in significantly reducing susceptibility to Coriolis motion sickness was demonstrated for each crewman. Nevertheless, although these drugs helped to mitigate symptoms, they were not completely effective in preventing or treating inflight motion sickness. In judging the efficacy of these drugs it should be noted that in several cases they were not taken until after symptoms had clearly appeared. It is also noteworthy that prior to the Skylab missions, limited efforts were made by a number of the crewmen to acquire adaptation to stressful motion stimuli. These activities took two forms. In one case the crewmen executed head movements while rotating in the chair designed for the Skylab M131 vestibular function experiments. These "vestibular training" sessions, which generally involved the execution of 150-200 head movements at a chair velocity of 20 rpm, were performed with the aid of anti-motion sickness drugs. These sessions were in addition to the normally scheduled M131 experiment preflight baseline data collection tests. Only 2 or 3 of these vestibular training sessions were performed with each crewman. In addition to the rotating chair activities the crew of Skylab 4 flew aerobatic maneuvers in high performance jet aircraft approximately one hour per week during the 6-8 weeks preceding their flight. These aerobatic activities were not
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supervised by the M131 experiment investigators. However, they may have been effective in that a gradual decrease in susceptibility to Coriolis motion sickness was observed during the course of implementing the M131 preflight tests. The limited attempts by the Skylab crewmen to acquire adaptation preflight appear to have been of no consequence as evidenced by the high incidence of inflight motion sickness. Even in crewmen who did not experience symptoms the value of preflight adaptation training was clouded because of the inflight use of anti-motion sickness drugs. A need to develop more effective countermeasures for space motion sickness clearly exists if future astronauts are to be spared the discomfort, inconvience and possible performance decrement caused by this syndrome. Current research efforts in this area are focusing on the development of new or improved pharmacological, as well as non-pharmacological countermeasures. Much of the new knowledge that has developed in this area since the Skylab Program, particularly that on anti-motion sickness drugs, has been contributed by Dr. Ashton Graybiel and his colleagues. Studies utilizing the Slow Rotating Room (SRR) at Pensacola revealed that a fixed dose combination of promethazine (25 mg) and ephedrine (25mg) provided outstanding protection against motion sickness (Graybiel et al., 1975b). This combination was as effective as the combination of scopolamine and dexidrine which had been established in previous studies as the best drug for preventing and treating motion sickness. The relative benefits of the promethazine plus ephedrine combination have been substantiated in more recent studies (Johnson et al., 1975; Graybiel and Knepton, 1977). These findings, combined with the knowledge that promethazine plus ephedrine provides longer lasting protection and appears to produce fewer side effects, makes this combination the drug of choice at the present time. Preliminary results from drug studies conducted during parabolic flight support this conclusion (Graybiel, pers. comm.). The Pensacola Slow Rotating Room and parabolic flight drug studies have also revealed great individual differences in response to anti-motion sickness drugs, implying that individual assessments must be made for maximal benefits. This finding assumes significance with regard to the expense and time that may become involved with selecting the optimum drug for individual flight crewmembers. The vast majority of drug studies to date have investigated the efficacy of drugs taken by mouth. As evidenced by the Skylab experience, drugs taken orally may be of little value if one is already manifesting symptoms. To deal with this problem research is underway to evaluate the efficacy of drugs administered by other routes. Scopolomine absorbed through the skin has been demonstrated to be a promising method for the long term control of motion sickness (Graybiel et al., 1976). Also, intra-muscular injections of promethazine and scopolomine given to subjects experiencing severe and acute motion sickness during parabolic flight have been very effective in alleviating symptoms (Graybiel, pers. comm.) Prominent side effects, noteably drowsiness, may occur with this type of treatment. Efforts are being made to better understand the behavioral and physiological side effects of various anti-motion sickness drugs.
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The majority of anti-motion sickness drug research conducted since the Skylab Program has emphasized the evaluation of drugs previously known to have anti-motion sickness properties. While the drugs now identified may prove, as a result of further research, to be the drugs of choice in the future, pilot studies are underway to identify new effective drugs. Some of these studies seek to isolate drugs which may modify neural and/or biochemical processes in specific areas of the central nervous system. This approach requires knowledge of the etiology of motion sickness, the pathways involved and how drugs might selectively effect activity in those pathways. In short, this approach deals with the site of drug action and is intended to control the causes of space motion sickness as opposed to merely suppressing symptoms. The development of a suitable animal model for space sickness will be important to the progress that can be made on such site of action drug studies. Two non-pharmacological countermeasures for space motion sickness are under investigation. The foremost of these involves investigations of neurosensory, especially vestibular system, adaptation processes. From these studies it is hoped that effective ground based laboratory techniques can be developed for imparting protective preflight adaptation to future astronauts. Past studies have demonstrated that vestibular adaptation can be acquired. However, the major question under investigation is whether or not such adaptation transfers in a positive fashion to the zero-g environment. To this end a variety of studies are being performed to evaluate such factors as rate of acquisition of adaptation, rate of decay of adaptation and most importantly, the degree to which adaptation acquired in one motion environment transfers to another motion environment. Many of these studies are being carried out with the Pensacola Slow Rotating Room. Also, in order to evaluate transfer effects which more closely approximate the transition to weightless spaceflight, parabolic flight will be utilized. In these planned studies, subjects who are susceptible to motion sickness induced by head movements during the zero-g phase of parabolic flight will be exposed to special vestibular adaptation training protocols and then be re-tested under the same provocative parabolic flight conditions. In addition to vestibular adaptation training a new approach is being applied to the development of an effective countermeasure for motion sickness. Investigators at the NASA-Ames Research Center are using bio-feedback and autogenic therapy to train subjects to control autonomic nervous system responses of the type associated with motion sickness. This is a novel approach which has met with varied success when used in other applications. Nevertheless, preliminary findings have been encouraging and research with this method will continue. Summary and conclusions The unexpectedly high incidence of space motion sickness experienced by the Skylab astronauts indicates convincingly that this syndrome represents a potential threat to the well-being and operational efficiency of at least some individuals who will fly future space missions. Effective means for dealing with this syndrome have proven to be elusive. Although generally considered to be a
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maladaptation phenomenon which occurs upon initial exposure to the novel weightless state, the specific mechanisms underlying space motion sickness are not well understood at this time. Just as importantly from a practical point of view, reliable methods for the a priori identification of individuals susceptible to this syndrome are presently lacking. Also, effective and operationally acceptable methods for preventing and treating symptomatology are not entirely adequate. In an effort to resolve these issues, NASA has undertaken a broad, interdisciplinary program of research. A large number of vestibular investigators at various government and university laboratories in the U.S. are applying their knowledge to this program. The majority of research in progress to define the etiology of space motion sickness is generally based on the premise that the syndrome is the overt manifestation of unresolved sensory conflict. In all likelihood, modifications in otolith behavior which occur during the first few hours in weightlessness are a primary factor in creating sensory conflict. The conflict may be in part intralabyrinthine in origin. That is, the normal synergy that is thought to exist between the semicircular canals and otoliths may be disrupted, thus resulting in modified neural outflow. Also, it is probable that intermodality conflict involving the visual, vestibular and the touch, pressure and kinesthetic senses occurs. The net result may be an inability of the central nervous system to properly integrate the mismatched sensory influx. Adaptive processes in the central nervous system presumably occur as evidenced by the gradual and complete recovery from symptoms of motion sickness. Extensive research, much of it involving the use of various electro-physiological, neuroanatomical, behavior and biochemical methodologies, is being directed toward the investigation of the sensory conflict theory. Aside from sensory conflict the Skylab program gave impetus to research on a new theory of space motion sickness, namely the fluid shift theory. This theory has its primary origin in the distinct observations of cephalad shifts of body fluids in weightlessness. It has been postulated that these fluid shifts may alter vestibular function as a result of creating subtle pressure changes in the labyrinthine fluids. Others have speculated that brain biochemical alterations may result from intracranial edema. Research to date with humans and animals has failed to support the fluid shift theory. Nevertheless, this theory warrants attention and will continue to be scrutinized. Of the various unresolved issues related to space motion sickness, the one which is most perplexing involves the development of predictors of susceptibility. The issue appears not to be one of simply making gross distinctions between high, moderate and low susceptibility to experimentally induced motion sickness. As previously indicated, all of the Skylab crewmen demonstrated moderate to low susceptibility during ground based tests, yet many of these individuals experienced inflight symptomatology. Most past research in this area has yielded results of limited usefulness. Clearly, new approaches are required. It would seem that emphasis should be placed on research wherein motion sickness is provoked largely by otolith stimulation and by exposure to conditions which evoke sensory conflict. That is, provocative and nonprovocative stimuli
Space motion sickness
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which attempt to activate those mechanisms thought to underly space motion sickness may prove to be a fruitful approach to the definition of valid predictive tests. Another promising approach involves determinations of rate of adaptation. Individuals who possess a propensity for rapid adaption to novel or stressful environments may experience fewer and shorter lived disturbances upon entry into zero-gravity. Also, other variables including predisposing psychodymic traits and intrinsic biochemical factors should and are being explored. The judicious use of parabolic flight is included among the resources that are being utilized in the implementation of these studies. Despite the insights that hopefully will be gained as a result of these ground based studies, it is anticipated that the final validation of predictive tests will require a series of controlled experiments with individuals who have flown previously in space, and more importantly, with those who will fly on the Space Shuttle missions. Modest progress has been made since the termination of the Skylab program in the identification of more effective pharmacological counter-measures for space motion sickness. On the basis of a series of studies using the Pensacola Slow Rotating Room and parabolic fight it has been demonstrated that the drug combination of promethazine and ephedrine (25 mg each) is a highly effective antimotion sickness drug for a substantial number of individuals. This combination has proven to be as efficacious as the long standing scopolomine and dexedrine combination, and typically produces fewer side effects. Advances have also been made in the development and testing of non-oral methods of drug administration. A small adhesive disc which permits the slow absorbtion of scopolomine through the skin has been successfully tested as a method of long term drug administration. More significant has been the treatment of severe and acute motion sickness by intramuscular injections of promethazine and scopolomine. Despite their usefulness, anti-motion sickness drugs may exact penalties in the form of detrimental side effects. Therefore, research is continuing to examine more thoroughly the behavioral and physiological consequences of using drugs as a countermeasure. In addition to the identification of new or improved drugs, the development of practical vestibular adaptation training methods continues to be of great significance. In this area efforts are being made to acquire more information related to the acquisition, retention and transfer of adaptation. Of paramount importance is whether or not adaptation acquired by whatever means preflight transfers in a beneficial manner to the space flight environment. Again, the Pensacola Slow Rotating Room and the parabolic flight aircraft have proven to be valuable research tools in the investigation of adaptation effects. Other research on non-pharmacological approaches to the development of counter measures currently includes the use of biofeedback training and autogenic therapy. Which of the countermeasures under investigation will be the most practical remains to be determined. Pharmacological methods are relatively easy to implement, especially inflight, and should involve a minimum of crew time. Such methods have the disadvantage, however, of creating potentially unacceptable side effects for some individuals, especially with prolonged drug use. Training
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methods avoid the problems associated with drugs, but may demand a considera b l e a m o u n t o f p r e f l i g h t c r e w t i m e . A s w i t h p r e d i c t i v e t e s t s , t h e final v a l i d a t i o n of countermeasures for space motion sickness, especially those employing t r a i n i n g t e c h n i q u e s , will r e q u i r e a s e r i e s o f c o n t r o l l e d s t u d i e s w i t h i n d i v i d u a l s w h o fly o n t h e S p a c e S h u t t l e m i s s i o n s . References Graybiel A. Personal communication. Graybiel A. and Lackner J. R. (1977) Comparison of susceptibility to motion sickness during rotation at 30rpm in the earth-horizontal, 10° head-up and 10° head-down positions. Avait. Space Environ. Med. 48(1), 7-11. Graybiel A. and Knepton J. (1977) Evaluation of a new antinauseant drug for the prevention of motion sickness. Aeait. Space Environ. Med. 48(9), 867-871. Graybiel A., Knepton J. and Shaw J. (1976) Prevention of experimental motion sickness by scopolamine absorbed through the skin. Avait. Space Environ. Med. 47(10), 1096-1100. Graybiel A., Miller E. F. II and Homick J. L. (1974) Experiment Mi31: Human vestibular function. In Proc. of the Skylab Life Sciences Syrup. Vol. 1, pp. 169-220. NASA TMX-58154. Graybiel A., Miller E. F. II and Homick J. L. (1975a) Individual differences in susceptibility to motion sickness among six Skylab astronauts. Acta Astronautica 2, 155-174 Graybiel A., Wood C. D., Knepton J., Hoche J. P. and Perkins G. F. (1975b) Human assay of anti-motion sickness drugs. Avait. Space Environ. Med. 46(9), 1107-1118. Hoffman R. B., Salinas G. A. and Baky A. A. (1977) Behavioral Analysis of killifish exposed to weightlessness in the Apollo-Soyuz Test Project. Avait. Space Environ. Med. 48(8), 712-717. Homick J. L. and Miller E. F. (1975) Apollo flight crew vestibular assessment. In Biomedical Results of Apollo, pp. 323-368. NASA SP-368. Homick J. L. and Reschke M. F. Unpublished data. Homick J. L. and Reschke M. F. (1977) Postural equilibrium following exposure to weightless space flight. Acta Otolaryngol 83, 455-464. Homick J. L., Reschke M. F., Moore M. J. and Anderson D. J. (1976) The effect of 28-days supine bedrest on vestibular system function. In Report of 28-day Bedrest Simulation of Skylab. Contract NAS9-14578, December. Hyatt K. H. Personal communication. Johnson W. H., Money K. E. and Graybiel A. (1976) Airborne testing of three anti-motion sickness preparations. Avait. Space Environ. Med. 47(11), 1214--1216. Parker D. E. (1977) Labyrinth and cerebral-spinal fluid pressure changes in guinea pigs and monkeys during simulated zero-g. Avait. Space Environ. Med. 48(4), 356-361 (1977). Reason J. and Graybiel A. (1973) Factors contributing to motion sickness susceptibility: adaptability and receptivity. In AGARD Conference on Predictability of Motion Sickness in the Selection of Pilots. AGARD-CP-109. Scheld H. W. et al. (1976) Killifish hatching and orientation, experiment MA-161. In Apollo-Soyuz Test Project Preliminary Science Report. NASA TMX-58173. Thornton W. E., Hoffler G. W. and Rummel J. A. (1974) Anthropometric changes and fluid shifts. In Proc. of the Skylab Life Sciences Syrup. pp. 637-658. NASA TMX-58154.