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The Otolith Organs as a Primary Etiological Factor in Motion Sickness: With a Note on "Off-Vertical" Rotation ASHTON GRAYBIEL AND EARL F. MILLER II Naval Aerospace Medical Institute SUMMARY Among investigators who agree that the vestibular organs are essential in producing motion sickness, there is either uncertainty or disagreement as to the roles of the otolith organs and the semi- circular canals which, under natural living conditions, furnish different information in response, respectively, to linear and angular accelerations. The shifting emphasis on the essentiality of the two organs is briefly traced, leaving in doubt today the role of the otolith organs formerly regarded as essential in the causation of seasickness and airsickness. This doubt has arisen by the demonstration that nystagmus, easily evoked when the canals are stimulated by angular or Coriolis accelerations, also may be manifested when a person is exposed to rectilinear accelerations or to "rotating linear acceleration vectors" (RLAV) in the absence of angular or Coriolis accelerations. Some experimental findings on man are reviewed. In one series, it was demonstrated that, in highly susceptible subjects, motion sickness may be experienced when the RLAV is within 4Â° of the physical upright. If the canals are indeed stimulated under these conditions, it implies a second highly effective means of stimulation inasmuch as, under the same circumstances, fluid in a model of the canals is not disturbed. In a second series of experiments, nystagmus was evoked in subjects regarded as possibly having residual otolith function, based on the ocular counterrolling test, but absent canalicular function, based on lack of response to high angular accelerations and to irrigation of the external canal with ice water. Although there may be doubt regarding the essentiality of the otolith organs in the genesis of motion sickness, there is little doubt but that their "influence" has been demonstrated in weight- lessness. Six subjects, symptom free while fixed in their seats during parabolic flight, manifested symptoms when required to carry out experimenter-paced head motions. Moreover, most subjects demonstrated a significant change in susceptibility when exposed to Coriolis accelerations under ground-based and weightless conditions, some manifesting an increase, others a decrease. While making preparations to study the effect of g-loading on susceptibility to motion sickness, it was accidentally discovered that a susceptible person subjected to passive rotation with his long body axis tilted 10Â° from the gravitational upright readily became motion sick. This early opportunity was taken to describe the device and to present some preliminary findings illustrating its uses. INTRODUCTION secondary influences which always are present; specific secondary etiologic factors may increase The primary etiological role of the nonacoustic or decrease susceptibility or, indeed, may be labyrinth in the genesis of motion sickness is facultative in this respect. declared by the fact that it is unique among sen- Among investigators who agree that the non- sory systems in conferring immunity after func- acoustic labyrinth is essential in the causation of tion is lost. This recognition of the essentiality motion sickness, there is still either lack of agree- of the labyrinth in no way minimizes the role of ment or uncertainty concerning the individual 53
54 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION and combined roles of the semicircular canals and the otolith organs. Until these roles have been elucidated, it may not be possible to pre- dict with scientific accuracy the susceptibility to motion sickness in novel force environments. It is the purpose of this report and the one to follow to summarize our present position regarding the etiologic roles of the two vestibular organs in causing motion sickness; a third report (Walter H. Johnson, "Secondary Etiological Factors in the Causation of Motion Sickness," this symposium) will deal with secondary etiological factors. BRIEF HISTORICAL REVIEW Historically, the shipboard force environment was the first to receive serious attention, and the acceleration patterns of that environment, in- terpreted in the light of the Mach-Breuer-Brown theory (ref. 1), seemed to implicate the otolith apparatus. Thus, when motion sickness was experienced under mild sea conditions, the linear accelerations were above threshold value while the angular accelerations were below 2 to 4 deg/ sec/sec which was then regarded as in the thresh- old range. Moreover, clinical observations revealed the absence of nystagmus, which was regarded as supporting evidence that the semi- circular canals were either not implicated or, if they were, played a small etiological role. On the other hand, the early experimental studies using vertical oscillations (refs. 2 and 3) and later studies using horizontal oscillations (refs. 4 and 5) clearly proved that rectilinear accelerations could readily evoke frank motion sickness in susceptible human and animal subjects. De Wit (ref. 6) in his monograph on seasickness published in 1953 concluded, "Seasickness is caused by overstimulation of the otolith system." The connection between the otoliths and sea- sickness was so strongly established that years elapsed before any doubt was expressed that, in- sofar as the etiological roles of the vestibular organs were concerned, there was any difference between seasickness and airsickness. In the early days of flight the etiological role of the force environment was often complicated by hypoxia, another cause of nausea and vomiting. That the majority opinion implicated the otolith apparatus in causing airsickness is shown indirectly by the impact made by a report (ref. 7) of observations that motion sickness in flight could be reduced or prevented by fixation of the head, thus impli- cating the semicircular canals more than the otolith apparatus. Motion-sickness studies using horizontal and vertical oscillators were reevaluated in the light of this finding. The angular component in hori- zontal swings and lack of head fixation in some experiments using vertical oscillations were underscored as generators of small angular accel- erations (ref. 8). Observations on seasickness were also reevaluated in the light of studies prov- ing that the thresholds of response of the semi- circular canals were far lower (ref. 9) than they were formerly thought to be. Although there was ample evidence that typical symptoms of motion sickness could be evoked in susceptible subjects by thermal stimulation and angular acceleration (ref. 10) involving the hori- zontal semicircular canals and by Coriolis accel- eration (refs. 11 and 12), it was the observations in the slow rotation room (ref. 13) which strongly emphasized the predominant etiologic role of the semicircular canals in causing motion sickness, at least in this force environment. Equally important was the evidence pointing away from the otolith apparatus by calling into question the validity of the Mach-Breuer-Brown theory under certain artificial stimulus conditions. The evidence consisted in the demonstration that nystagmus can be evoked when a person is exposed to (1) rectilinear accelerations (refs. 14 and 15), (2) constant angular velocity when rotated about a coplanar Earth-horizontal axis (ref. 16), and (3) a rotating linear acceleration vector in the absence of angular motion (in a counter- rotating room) (ref. 17). In addition to studies on man, experiments using animal subjects with selective injury to the canalicular system showed reduced or abolished susceptibility to motion sickness (ref. 18), and electrophysiological studies revealed what ap- peared to be canalicular responses to linear accelerations (ref. 19). In summarizing this brief review, it is evident that there has been a gradual shift in the majority opinion regarding the roles of the two vestibular
OTOLITH ORGANS AS A FACTOR IN MOTION SICKNESS 55 organs in the genesis of motion sickness. The early experimental studies interpreted in the light of the Mach-Breuer-Brown theory seemed to demonstrate the essentiality of the otolith organs. Today, the evidence suggests that the canals are essential organs in the genesis of motion sickness and, by implication, leave in doubt the role of the otolith apparatus. EVIDENCE IMPLICATING THE OTO- LITH APPARATUS IN THE CAUSATION OF MOTION SICKNESS The Counterrotating Room A counterrotating room (ref. 20) is chosen to typify the force environment in devices either not generating angular or Coriolis accelerations or at least not generating them at the time motion- sickness symptoms are evoked. Among 18 healthy subjects with normal function of the canals as revealed by the threshold caloric test and normal function of the otoliths as revealed by the oculogravic illusion test, 11 manifested symptoms of motion sickness in the counter- rotating room (CRR), six did not, and in one the evidence was in doubt. Two experienced symp- toms while rotating at 10 rpm, one after 14, and the other after 30 minutes. At the effective radius of 2 feet in the room, the rotating gravi- toinertial vector deviated from the physical up- right of the subject by less than 4Â°. Three other subjects experienced symptoms while rotating at 15 rpm for 30 minutes or less, with the rotating vector less than 9Â° from the physical upright. There can be no question that, in these sub- jects, the otolith organs were stimulated in an unusual pattern, even at the lower stimulus level, inasmuch as the stimulus exceeded the thresh- old of response (ref. 21). It is equally certain that the cupula-endolymph system of the canals was not stimulated, at least in a normal manner; the fluid in a glass model was not even disturbed. If the canals were stimulated at the lower ef- fective stimulus level, the rotating linear accel- eration vector evoking symptoms would represent a second fairly efficient stimulus mechanism, inasmuch as the accelerative forces involved were small. If the canals were not stimulated, the question of the significance of their resting discharge arises and whether it was modulated by the unusual input from the otolithic receptors, and, in this way, would give rise to symptoms. The fact that nystagmus can be evoked at higher stimulus levels in the CRR (ref. 20) and in other devices when angular or Coriolis accel- erations are absent is a matter of great and con- tinuing interest and has been reviewed in NASA SPâ115. Although the definitive experiment has not been performed, nystagmus evoked under the above conditions constitutes the best evi- dence that the canals may be stimulated at low as well as at high stimulus levels. Experiments on Persons With Vestibular Defects Labyrinthine-Defective Subjects Eleven persons with severe bilateral laby- rinthine defects (L-D subjects) have participated in many experiments for a period of over 10 years, and during this time functional tests have been conducted on several occasions (table 1) (ref. 22). None has experienced motion sickness in any of our laboratory devices (refs. 13 and 20) or in the air (ref. 23). During their exposure at sea they were free from symptoms characteristic of motion sickness; two occasions in this regard deserve comment. On one occasion (ref. 24) several of them had not recovered from a nauseating dose of sirup of ipecac at the time they were exposed to turbulent seas in a boat; recovery was unevent- ful despite the conditions. On the second occa- sion (ref. 25) during a severe Atlantic storm when living conditions aboard the ship were abnormal, one subject (HA) reported "slight nauseaânot gastrointestinal"; other symptoms checked in the prepared questionnaire form were not remarkable under the circumstances. Based on the clinical findings in these L-D subjects (table 1), it was concluded that some otolithic function might be left. In six of them the likelihood of residual canalicular function seemed to be nil in view of the lack of response both to ice-water irrigations and to exposure to high angular accelerations, yet they manifested nystagmus when exposed to Earth-horizontal rotation at 12 rpm (ref. 16). The conditions in the latter experiment were favorable for stimula- tion of any residuum of the otolithic apparatus, where differences in specific weight between the otoliths and surround were great, but not
56 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION TABLE I. âClinical Findings in 11 Deaf Persons With Bilateral Labyrinthine Defects Subject Age Auricular defects Hearing ' Threshold response, caloric test Counterroll index, minutes of arc.2 maximum tilt 3 Onset year, age Etiology R L R L 50Â° 75Â° 48 13 12 Nil Nil N.R..Â« 10Â° C. 3 min N.R., 10Â° C, 74 74 3 min Greenmun 48 26 Mastoiditis Nil 3=145 Nil 160 N R N R 60 76 Gulak 4i 3= 145 Nil 10Â° C, 40 sec.... N.R., 2.8Â° C, 10 min 10Â° C, 40 sec N.R., 2.8Â° C, 10 min N R 30Â° C 89 Harper 29 13 71 47 53 Jordan 34 29 Nil Nil N R 3 min 126 176 109 82 30 85 117 36 6 *115 ^ no 10Â° C. 40 sec N.R.I?) 73 63 21 71 110 22 Myers 25 33 26 25 25 8 12 3 12i 3i Nil Nil Nil Â» 130 s=135 Nil Nil Nil Â» 135 s* 130 N.R., 2.8Â° C, 10 min N.R., 2.6Â° C, 3 min 9.8Â° C. 40 sec 7.9Â° C. 40 sec Peterson N.R., 2.6" C. 3 min Not tested (infection) 11.0Â°C.3min.... Piper Steele 1 0.0Â° C. 3 min.... 2.8Â° C, 10 min.... Zakutney 2.8Â° C. 10 min.... 1 Response to white noise up to 160 decibels. 2 One-half the sum of maximum roll right and left (minutes of arc). 3 Angular displacement of body from vertical in frontal plane. * N.R. âNo response. for the sensory epithelium of the canals where differences in specific weight were very small. The dilemma is created by the fact that in a normal person, nystagmus is so easily evoked by an artificial stimulus to the canals, whereas in the otolith apparatus the typical response is a compensatory movement of the eyes. Henriks- son (personal communication) believes that on approaching a critical rate of cyclic stimulation of the otolith apparatus, compensatory move- ments might become nystagmic. In any event, the findings in these L-D subjects demonstrate a clear separation between evoking nystagmus and motion sickness. Partial Loss of Vestihular Function The fact that persons with loss of vestibular function are insusceptible to motion sickness raises the problem of how much loss confers immunity. In table 2 are shown the relevant clinical findings in eight persons with abnormal values on the threshold caloric test (ref. 26) or ocular counterrolling test (ref. 27), or both. Interpretation of the findings is made difficult because of the great individual variance in suscep- tibility to motion sickness and in ocular counter- rolling values among clinically normal persons. The first subject was "discovered" fortuitously, during a demonstration in the slow rotation room (SRR), when he failed to manifest any signs of motion sickness during a variety of activities when rotating at 10 rpm. At that time he was unable to stand more than a few seconds on one
OTOLITH ORGANS AS A FACTOR IN MOTION SICKNESS 57 leg. About a year previously he experienced acute symptoms referable to the labyrinth follow- ing a dive; these gradually declined but per- sisted over a period of about 2 weeks. There was no opportunity for systematic tests on the occasion of his first visit, but 2 years later he was seen again. The threshold caloric test values were above normal, and his performance on the postural equilibrium test battery was below normal despite the fact that he had been an exceptionally gifted athlete. After 85 head motions at 10 rpm in the SRR, he manifested severe malaise, indicating that susceptibility was in the normal range. Although the findings are meager, it is reasonable to conclude that his susceptibility to SRR sickness had increased in the 2-year interval. The second subject was a professional diver who, during the course of a routine evaluation, manifested a threshold caloric test value far above normal on the left side but no other definite abnormality. His susceptibility to SRR sickness was in the normal range. The third subject, a professional diver, was seen on three occasions. Aside from a slight hearing loss, the only abnormality revealed was a low ocular counterrolling index on two occa- sions. His susceptibility to motion sickness was within the normal range. The remaining five subjects were similar in their lack of susceptibility to motion sickness. Four had no response to irrigation of the ear with ice water on one side and varying increases in threshold level on the opposite side. It is note- worthy that the ocular counterrolling index was within the normal range in subjects 5 and 7 (table 2). More information of this kind is needed, but it would appear that loss of canalicular function is more critical than loss of otolithic function in reducing susceptibility to motion sickness. Experiments in Parabolic Flight Observations in parabolic flight (ref. 28) have fur- nished some evidence that the otolith apparatus plays a role in the genesis of motion sickness even though this does not demonstrate its essentiality. Susceptibility to motion sickness was compared in 15 subjects exposed to Coriolis accelerations in the weightless phase of parabolic flight and under ground-based conditions. The accelerations were generated by requiring the subject to move his head in a standardized manner while rotating in a chair device. Susceptibility was measured in terms of the number of head movements re- quired at a given angular velocity to evoke severe malaise. It was found that susceptibility aloft either increased (eight subjects) or decreased (seven subjects), compared with that underground- based conditions (fig. 1). When the subjects were ranked in order of increasing susceptibility under ground-based conditions, it was found that this order was preserved under weightless condi- tions up to subject 7 but not beyond. Inasmuch as parabolic flight exclusive of the weightless phase may properly be regarded as a force environment tending to evoke motion sick- ness, the reduced susceptibility manifested by some subjects during the test procedures was regarded as a conservative valid finding, while in- creased susceptibility would have to be inter- preted with caution. The further demonstration, however, that six subjects experienced symptoms 130 en BO 2 90 Â§60 MOTION SICKNESS SUSCEPTIBILITY 0, .1, OKI, FIGURE 1. âComparison of Coriolis (motion) sickness sus- ceptibility of 15 subjects measured in weightlessness and under terrestrial conditions. 0*: no symptoms, except in subject HA who experienced moderate malaise (M II A) on only his first test at zero g. M III: severe malaise. (From ref. 28.)
58 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION â¢ C u .i -S .i Â§ Â£ Je '3 o o C IN i 'â¢^y r fctÂ£^e*T'^ui._^ Â«iffl MÂ§ ^^c^^ga^S;-; * = S od z Â£ Â£ "c c S i> e i/ C . = o Â£^Â£ 5 H â¢2 s s c o rinthine Finn â¢o S 1 i i -o .^ .t: f Â£/", ^ "â¢ L/* CO Â« 1 S1 ^ a o -Â«; i 1 2 |3 0 0 V Â» 1* i i * i ~ if * Â£ 2 c 1 Jl ]i |! Â«5 <j 'Â£ =â¢ > ( </3 c X 1 * â ^ ^H ^^ ro â¢â â "" *â¢ 2 | Â§ SÂ£ t - .. __; oJ "2 -= 'C -c: o â * CÂ£ ^ BK u- O o .S /^ 7 'SC.ii-aJC^oE t o X X Z Z. .i? 52 3 >d jf Z | ^ '^3 Â£<Â§ a 4Â» o Ln oo q = ' -c Susceptibili Scores ( ^ -c a: S S 1 SJ A 1 2 1 J fc A t A fe ? C C S. Z c S "^j V 1 g u K >, B E ! 1 liU s 1 i A |2 Â§-.2 t A Â£ A Â£ A S" Â£ i . H S | > X Q c a -= â¢Â£ "i Â« a. .> i -3 0 C 5 J .Â£ -t ^ â¢S Ed c 1 1 1 Q Q c/) 5 t fe ; 1 1 s -o s^= ^ -3 -3 w 0) Â£ J Â£ '-J U. O Â£Â«. H â¢< eo * s s ? 5 3 % S ^, s ? S 31 i"â¢ j^ C*3 f^ in 3 K
OTOLITH ORGANS AS A FACTOR IN MOTION SICKNESS 59 - O. . 5 fe = 3.* . 1 Si ~ 15 * c u -3 .2 - i a -a â¢;: 111 lei JS i | t 1 i c n >, i * , K >; u d C M -ii O'â 0â n & iB 0 Â». X u * c-ecrtfriIjDp^cO JS ^-S^lco-^^j:- g-JI g-fe2S^o-j;A dicated. a. 7i *s 0} 4) ,* U ,* 0) s * "t to 3 i> 2 Â« !2 L. co u. ra u b CO 'i u â¢ Â»^ u .4, u a Â£. 'E â¢â ,f, â¢â¢â¢ X c u .Â£ =5 .Â£ ^ u o JT S S â¢^ h V "1 - 1 o 3 ;; bÂ£i c a t "u 'a '5 c X U. o u. s s ^ Â» i s s $ 1 â¢ B â¢ ^ 'i * 'o t- W s V O " C X â 24 AS 4S. AS^ AS AS 20 PARABOLA urn a Mil - *?* * ,"Â», 12 | Mm 8 4 0 MM â¢ AL AU FO SC SM WA SUBJECT O HÂ«x) Stotonaj AS â¢ Asymptomatic ^^ Ma A Moderate Maiaise â¢ mod ActiveIy Moved MDI- Severe MataIte FlGURE 2. âMotion sickness susceptibility in zero g. Effect among six susceptible subjects of active head movements relative to the restrained condition upon motion-sickness susceptibility measured in terms of the number of parabolas required to provoke Malaise III. (From ref. 28). while making head motions in the absence of rota- tion (fig. 2) not only adds to the validity of the findings indicating increased susceptibility but also demonstrates experimentally what had been reported by Soviet cosmonauts (refs. 29 and 30). It seemed reasonable to conclude that any sig- nificant changes in susceptibility during weight- lessness were due very largely to changes in otolithic modulating influences resulting from the lifting of the gravitational load. There is a large amount of other evidence that canalicular responses are modified by linear ac- celerations in man (refs. 31 to 33) and that suscep- tibility to motion sickness is affected by increased ^â¢-loading. OFF-VERTICAL ROTATION While making preparations to conduct experi- ments with the object of determining the in- fluence of g-loading on susceptibility to motion sickness, it was found that symptoms were readily evoked in most normal persons when they were
60 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION passively rotated with the base of a chair device tilted 10Â° away from the gravitational upright. Although a full report is in preparation, it seemed worthwhile to make a brief account here inas- much as the off-vertical rotation (OVR) affords an exceptionally precise means of controlling the stressful accelerations. Exposure Device and Procedure A Stille rotating chair, model RS-3, was modified (fig. 3) for use as a rotating tilted chair. It was mounted on a platform which could be tilted up to 20Â°, either by means of a hand crank or an electric motor, and the degree of tilt could be read from a large protractor. A rigid bracket was added with provision for supporting and adjusting both a dental appliance to fix the sub- ject's head and a goggle device (ref. 34). The latter device included a monocular target, con- sisting of a dimly illuminated line of collimated light, which the subject could rotate about its center to indicate the upright or raise or lower to indicate the "horizon"; visual and automatic readouts were available. Provision was made for centering the subject's head precisely over the center of rotation and f\1 \\ â¢â¢â¢â¢â¢ri" 'â¢â¢ \".' â¢'â¢'â¢'â¢' â¢â¢-fiJ ^Â®v,, m :\:::::V" >l ; ""'"-t^. 3V a j -rr^ /â¢ . A.. â¢ 4-/â¢â¢ \ \ FIGURE 3. â Off-vertical rotating chair device; slide mecha- nisms for positioning subject not shown. for proper counterbalancing to ensure smooth rotation at any degree of tilt. The rotation was programed on a time axis involving periods of acceleration at 0.5 deg/sec/sec for 30 seconds, followed by periods of constant velocity for 6 minutes until either the endpoint described below was reached or 6 minutes at 25 rpm were com- pleted. In effect, this program represented unit increases of 2.5 rpm every 6.5 minutes after the initial step. Thus, the endpoint indicated that temporal summation of the disturbing effects had exceeded the capacity for homeostatic adjustment over a period of time, and this served as an index of susceptibility. The endpoint also could be expressed in elapsed time at terminal velocity. With each revolution of the OVR device, the subject's head also rotated out of phase about the yaw and roll axes. Thus, while turning at con- stant velocity, the vestibular organs are exposed to a rotating linear acceleration vector. The ef- fects on the paired maculae of utricle and saccula are unusual in that the horizontal component of this specific force with respect to the subject con- tinually changes direction. The question whether the semicircular canals also are stimulated by a rotating linear acceleration vector has been discussed above. The endpoint used in this series of observa- tions, "moderate malaise" (M II A), has been described elsewhere in detail (ref. 35): the diag- nostic criterion on which it is based is sum- marized in table 3 (ref. 35). Subjects Five of the deaf persons with bilateral labyrin- thine defects mentioned in table 1 and 66 normal males participated. The five L-D subjects, 28 to 54 years of age (GR, GU, MY, PE, and ZA). were in good health, and each had participated in many similar experiments: hence, they were regarded as sophisticated subjects. The control group of 66 subjects ranged in age from 19 to 33 years; 34 of them were in the Navy aviation officer training program, 30 were Navy enlisted men, and 2 were Navy medical externs. All had met the required Navy medical qualifica- tions and were in good health.
OTOLITH ORGANS AS A FACTOR IN MOTION SICKNESS 61 TABLE 3. â Diagnastic Categorization of Different Levels of Severity of Acute Motion Sickness Category Pathognomonic, 16 points Major, 8 points Minor, 4 points Minimal, 2 points AQS.1 1 point Nausea Il 2 Epigastric aware- Skin retching. Il1. Pallor 111 Pallor II fort. Pallor I ness. Il1 II I tive warmth, * II. III II I Drowsiness Ill II Pain Headache, * II Central nervous system... Dizziness: Eyes closed, Â» II. Eyes open, HI. Levels of Severity Identified by Total Points Scored Frank sickness (S) ^ 16 points Severe malaise (M III) 8-15 points Moderate malaise A (M Il A) 5-7 points Moderate malaise B (M II B) Slight malaise (MI) 1-2 points 3-4 points 1 Additional qualifying symptoms. 2 III, severe or marked: II, moderate: I, slight. General Procedure Each subject was carefully instructed in the best manner of reporting the symptoms. This was important, not only for the observer to estimate the level of severity of the signs and symptoms but also to avoid overshooting the endpoint (M HA) because of the rapid increase in severity of symptoms once they became definite. Under the conditions of this test, the observer always had a good opportunity to note and record changes in facial color and expression and the onset of sweating. The subject was queried repeatedly and, with the onset of moderate malaise, the device was quickly tilted to the upright to abolish the stressful stimuli, and deceleration effected at the same rate as that of the acceleration. In conducting susceptibility tests the subject's eyes were covered with a padded shield. Unless otherwise indicated, normal subjects were exposed to the programed accelerations de- scribed above while tilted 10Â° away from vertical. This program was altered for the group of L-D subjects. On one occasion all except ZA were exposed for 6 minutes at terminal velocities of 10, 20, and 30 rpm, and all except GU were exposed on other occasions at 30 rpm for periods of 10 minutes or longer. Results Motion Sickness Symptoms of all but 6 of the 66 control subjects reached the endpoint during the "standard" test, and the variance in their susceptibility is shown in figure 4. More than half reached the endpoint at the three velocities of 7.5, 10.0, and 12.5 rpm. Of the six not reaching the endpoint, three were available for retesting. Of these, two experi- enced M IIA when the tilt was increased to 20Â°, as indicated by the dotted columns in figure 4. Under the test as programed, once symptoms appeared, they waxed rapidly, necessitating alertness on the part of subject and experimenter to avoid overshooting the endpoint, as illustrated in figure 5. This could be prevented by using another mode; e.g., selecting the velocity at which symptoms would be expected. None of
62 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION 0 tI râ-I- in n^ FIGURE 4. â Differences in susceptibility to motion sickness (endpoint, M II A) among 66 subjects exposed to off-vertical rotation according to the programed stress indicated on the abscissa; among the six not experiencing symptoms at 10Â° tilt, three were available for retesting at 20Â° tilt. Two of the three reached the endpoint as indicated by the dashed lines. the five L-D subjects experienced symptoms of motion sickness. Sensations During Rotation There were more uniformities than differences between normal and L-D subjects in reporting their perceptions with eyes covered during rota- tion. During periods of constant velocity, both LâD and normal subjects sensed the motion not as rotation but as if they were revolving, and, except in a few instances, sensed the direc- tion as being opposite to that in which the chair was turning. Although a detailed analysis has not been made of the cyclic variations in the subjects' experiences and the variations from one experience to another, they were reminiscent of those experienced in the counterrotating room (ref. 20). In general, there was a greater tendency for the L-D subjects to become disoriented than was the case for the normal controls, and there were greater individual differences among the L-D subjects in reporting their subjective impressions with regard to their orientation to the gravitational upright and in FIGURE 5. âDemonstrating relatively rapid increases in level of severity of symptoms among seven subjects varying in susceptibility to motion sickness when exposed to off-vertical rotation at 10Â° tilt. FIGURE 6. â Actual recording oj a subject's dynamic settings of the visual target to the "horizon" (pitch) and the vertical (roll) during 10Â° off-vertical rotation at 5 rpm. the shape of the "envelope" in which they revolved. Estimations of Deviations From the Vertical and From the Horizon A few recordings have been made of tne sub- jects' settings using the goggle device described above. The subject's task was to maintain the
OTOLITH ORGANS AS A FACTOR IN MOTION SICKNESS 63 dim broken line of light in darkness at the vertical and the center gap at the level of the horizon. In figure 6 are shown typical settings of a normal subject. It is seen that this rather demanding task Was accomplished quite well. A few normal subjects became "confused" or "disoriented," and a larger number performed poorly. The L-D subjects experienced much more difficulty than normal subjects in making the settings. One evidence of this was their need for a greater excursion of arc in setting the target to the "horizon"; they kept hitting the "stops." Comment The effectiveness of the provocative test just described for motion sickness is shown by the small angle of tilt required to evoke symptoms in 90 percent of subjects available at an air station. The reliability, i.e., test-retest, was high. The passive character of the exposure minimized fatigue, as compared to that experienced when making active head movements. The scoring index accurately ranked the subjects inasmuch as a given value represented the same exposure history for all. Although only one programed mode was used, variations could be made to fit different purposes. The OVR device is useful in exploring further the visual and non- visual subjective experience, both in normal persons and in persons with labyrinthine defects. REFERENCES 1. BORING, E.: Proprioception of the Inner Ear. Sensation and Perception in the History of Experimental Psy- chology, E. Boring, ed., Appleton-Century, 1941, pp. 535-544. 2. SJOBERG, A.: Experimented Studien iiber den Aus- liisungmechanismus der Seekrankheit. Acta Oto- Laryngol.. suppl. 14, 1931, pp. 1-136. 3. ALEXANDER, S. J.: COTZIN, M; HILL. C. J., JR.; Ric- ciUTI. E. A.; AND WENDT. G. R.: Wesleyan University Studies of Motion Sickness: III. The Effects of Vari- ous Accelerations Upon Sickness Rates. J. Psychol., vol. 20, 1945, pp. 3-8. 4. JOHNSON, W. H.; AND TAYLOR, N. B. G.: Some Experi- ments on the Relative Effectiveness of Various Types of Accelerations on Motion Sickness. Aerospace Med., vol. 32, 1961, pp. 205-208. 5. MANNING, G. W.; AND STEWART, W. G.: Effect of Body Position on Incidence of Motion Sickness. J. Appl. Physiol., vol. 1, 1949, pp. 619-628. 6. DE WlT, G.: Seasickness (Motion Sickness). Acta Oto- Laryngol., suppl. 108, 1953, pp. 1-56. 7. JOHNSON, W. H.; STUBBS, R. A.; KELK, G. F.; AND FRANKS, W. R.: Stimulus Required to Produce Motion Sickness. I. Preliminary Report Dealing With Im- portance of Head Movements. J. Aviat. Med., vol. 22, 1951, pp. 365-374. 8. KEIST, B. F.; SHEELEY, W. F.; BYERS, J. M., JR.; AND CHINN, H. I.: Relative Effects of Head Immobilization and Medication on the Incidence of Airsickness. Report 55â78. School of Aviation Medicine, USAF, Randolph AFB, Tex., 1955. 9. GRAYBIEL, A.; KERR, W. A.; AND BARTLEY, S. H.: Stimulus Thresholds of the Semicircular Canals as a Function of Angular Acceleration. Am. J. Psychol., vol. 61, 1948, pp. 21-36. 10. BARANY, R.: Physiologic und Pathologie des Bogengangap- parates beim Menschen. (Funktionspriifung des Bogengangapparates.) Klin. Studien. Deuticke, Wien, 1907. 11. SCHUBERT, G.: Die physiologischen Auswirkungen der Coriolis-Beschleunigungen bei Flugzeugsteuerung. z. Hals-Nas.- u. Ohrenheilk, vol. 30,1932, pp. 595-604. 12. SPIEGEL, E. A.; OPPENHEIMRR, M. J.; HENNY, G. C.; AND WYCIS, H. T.: Experimental Production of Motion Sickness. War Med., vol. 6, 1944, pp. 283-290. 13. GRAYBIEL, A.; CLARK, B.; AND ZARRIELLO, J. J.: Obser- vations on Human Subjects Living in a "Slow Rota- tion Room" for Periods of Two Days. Arch. Neurol., vol. 3, 1960, pp. 55-73. 14. JoNGKEES, L. B. J.; AND PHILIPSZOON, A. J.: Nystagmus Provoked by Linear Accelerations. Acta Physiol. Pharmacol. Neerl., vol. 10, 1962, pp. 239-247. 15. NlVEN, J. I.; HlXSON, W. C.; AND CoRREIA, M. J.: Elicitation of Horizontal Nystagmus by Periodic Linear Acceleration. Acta Oto-Laryngol., vol. 62, 1967, pp. 429-441. 16. GUEDRY, F. E., JR.: Orientation of the Rotation-Axis Relative to Gravity. Acta Oto-Laryngol., vol. 60, 1965, pp. 30-48. 17. MONEY, K. E.: Discussion following paper by F. E. Guedry, Jr., Influence of Linear and Angular Accelera- tions on Nystagmus. Second Symposium on the Role of the Vestibular Organs in Space Exploration, NASA SP-115, 1966, pp. 196-198. 18. MONEY, K. E.; AND FRIEDBERG, J.: The Role of the Semi- circular Canals in Causation of Motion Sickness and Nystagmus in the Dog. Can. J. Physiol. Pharmacol., vol. 42, 1964, pp. 793-801. 19. BENSON. A. J.; Gi EDRY, F. E., JR.; AND JONES. G. M.: Response of Lateral Semicircular Canal Units in Brain Stem to a Rotating Linear Acceleration Vector. J. Physiol., vol. 191, 1967, pp. 26P-27P.
64 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION 20. GRAYBIEL, A.; AND JOHNSON, W. H.: A Comparison of the Symptomatology Experienced by Healthy Persons and Subjects With Loss of Labyrinthine Function When Exposed to Unusual Patterns of Centripetal Force in a Counter-Rotating Room. Ann. Otol., vol. 72, 1963, pp. 357-373. 21. GRAYBIEL, A.; AND PATTERSON, J. L., JR.: Thresholds of Stimulation of the Otolith Organs as Indicated by the Oculogravic Illusion. J. Appl. Physiol., vol. 7, 1955, pp. 666-670. 22. GRAYBIEL, A.: Orientation in Aerospace Flight. Spe- cial Report 66-6. NASA Order R-93. Naval Aero- space Medical Institute. Pensacola, Fla., 1966. 23. COLEHOUR J. K.; AND GRAYBIEL, A.: Excretion of 17- hydroxycorticosteroids, Catechol Amines, and Uro- pepsin in the Urine of Normal Persons and Deaf Subjects With Bilateral Vestibular Defects. Aero- space Med., vol. 35, 1964, pp. 370-373. 24. GRAYBIEL, A.: Functional Disturbances of Vestibular Origin of Significance in Space Flight. Second Inter- national Symposium on Man in Space, Paris, 1965, Springer-Verlag, Wien and New York, 1967, pp. 8-32. 25. KENNEDY, R. S.: GRAYBIEL, A.: McDoNoucH, R. G.: AND BECKWITH, F. D.: Symptomatology Under Storm Conditions in the North Atlantic in Control Subjects and in Persons With Bilateral Labyrinthine Defects. Acta Oto-Laryngol., vol. 66, 1968, pp. 533-540. 26. McLEOD, M. E.; AND MEEK, J. C.: A Threshold Caloric Test: Results in Normal Subjects. NSAM-834. NASA Order R-47. Naval School of Aviation Medi- cine, Pensacola, Fla., 1962. 27. MILLER, E. F., II: Counterrolling of the Human Eyes Produced by Head Tilt With Respect to Gravity. Acta Oto-Laryngol., vol. 54, 1961, pp. 479-501. DISCUSSION FOLLOWING ALL OF SESSION II Gernandt: What about the splanchnic nerve. Dr. Money? Money: These nerves are present, but since the animals after operation failed to vomit to copper sulfate (rather, they did not fail, but the thresholds were markedly increased by a factor of 10), it was concluded that the drug was taking the blood route to the chemoreceptor trigger zone. It was con- cluded that the viscera was denervated, at least from the point of view of the vagus nerve and the sympathetic nerve. As Dr. Gernandt points out, there are other nerves to the viscera as well. We can take this as referring only to those which were in fact eliminated by Wang, Chinn, and Renzi. (Postsymposium note: The sympathectomy as described by these authors, by removal of the sympathetic chain in one unbroken thread, would, in fact, divide the splanchnic nerve.) Waite: Concerning the parabolic flight data presented early in Dr. Grayhiel's paper, I should like to comment that a Soviet investigator, Yuganov, reported three groups, in- cluding subjects who demonstrated no change whatsoever. Does Dr. Graybiel think he might obtain such a group if he were to test a greater number of subjects? 28. MILLER, E. F., II; GRAYBIEL, A.: KELLOGG, R. S.: AND O'DONNELL, R.: Motion Sickness Susceptibility Under Weightless and Hypergravity Conditions Generated by Parabolic Flight. Aerospace Med., vol. 40, 1969. pp. 862-868. 29. KOMENDANTOV, G. L.; AND KOPANEV, V. I.: Motion Sick- ness as a Problem of Space Medicine. Problems of Space Biology, vol. 2, N. M. Sisakyan and V. I. Yaz- dovskiy, eds., JPRS TT18, 395. Joint Publications Research Service, 1963. pp. 84-89. 30. GAZENKO, O.: Medical Studies on Cosmic Spacecraft "Vostok" and "Voskhod." Bioastronautics and the Exploration of Space, T. C. Bedwell. Jr., and H. Strug- hold, eds.. Air Force Systems Command, Brooks Air Force Base, Tex., 1965, pp. 357-384. 31. BENSON, A. J.; AND WHITESIDE, T. C. D.: The Effect of Linear Acceleration on the Response to Angular Ac- celeration in Man. J. Physiol., vol. 156, 1961, pp. 6P-7P. 32. LANSBERG, M. P.; GUEDRY, F. E., JR.; AND GRAYBIEL, A.: Effect of Changing the Resultant Linear Acceleration Relative to the Subject on Nystagmus Generated by Angular Acceleration. Aerospace Med., vol. 36, 1965, pp. 456-460. 33. BENSON, A. J.; AND BODIN, M. A.: Interaction of Linear and Angular Accelerations on Vestibular Receptors in Man. Aerospace Med., vol. 37, 1966, pp. 144-154. 34. GRAYBIEL, A.; MILLER, E. F., II; BILLINGHAM, J.: WAITE, R.; BERRY, C. A.; AND DIETLEIN, L. F.: Vestibular Experiments in Gemini Flights V and VII. Aerospace Med., vol. 38. 1967, pp. 360-370. 35. GRAYBIEL. A.: WOOD, C. D.; MILLER, E. F., II; AND CRAMER. D. B.: Diagnostic Criteria for Grading the Severity of Acute Motion Sickness. Aerospace Med., vol. 39, 1968, pp. 453^55. Graybiel: I would think so. We did find a bimodal dis- tribution, not a complete separation into two groups. These findings are suspect because in parabolic flight there is the high-g pullup and pullout which may influence suscepti- bility to motion sickness in the weightless phase. But we used subjects who were familiar with this maneuver and for the most part were not bothered in standard parabolic flights. They were rotated just during the weightless period. I believe that, qualitatively, our findings will stand up. I think the evidence that the nystagmus runs on for a much longer time in weightlessness also tends to indicate the in- fluence probably of the otolith apparatus on the canal response. Schiff: My comment is on Dr. Money's paper and relates to work done at the Army Chemical Research Center some time prior to my retirement from the Navy. We performed a series of experiments in which, in the first case, we injected diisopropyl fluorophosphate (DFP) or some analog which destroyed the acetylcholinesterase. As soon as this oc- curred, the animal would walk in circles, the so-called
DISCUSSION OTOLITH ORGANS AS A FACTOR IN MOTION SICKNESS 65 adversive syndrome. In another cat we put cocaine next to the round window. The animal would again walk in circles. Then we put the G-agent or DFP against the round window. This substance permeates most tissues highly effectively. No circular motion occurred in the animal. The conclusion would seem to be that it was a central phe- nomenon, since the acetylcholinesterase exists in the brain portion. As far as in the peripheral labyrinth is concerned, acetylcholinesterase exists as a result of the efferent system, but we have no way of measuring efferent effect. From an afferent point of view, the animal did not walk in circles, which meant there was no acetylcholine involved. Baldes: Dr. Graybiel, have you tilted your seat 10Â° for- ward from the vertical? Graybiel: The base of the chair is 10Â° away from the vertical. As it rotates, a person in the chair changes his position all the time. We call it off-vertical rotation. I would like to ask Dr. Money a question regarding the use of vomiting as an endpoint or the guiding system in motion sickness. Vomiting is not an initial cardinal symptom of motion sickness; in my opinion it is a complication. By the time vomiting occurs, many preceding events have taken place. The initial cardinal symptoms are such manifesta- tions as sweating, pallor, drowsiness, and stomach aware- ness. In another paper I have shown a hygrometer recording demonstrating that, as a result of one single head movement in the slow rotation room, there is a slight increase in sweat- ing and a little change in finger temperature (ref. 9 of text). These changes occur very quickly indeed, whereas, vomiting, as Dr. Money pointed out, is usually a rather late symptom unless the stress is extremely severe. Money: Of course, there are many other things besides vomiting that go with motion sickness. However, 1 meant to point out that I see motion sickness as basically a mys- tery. It is an anomaly, or what have you. It happens even in fish. It happens in man, monkeys, cows, horses, and dogs, and why should such an antiteleological phenomenon occur in so many different species? When that question is an- swered, the essence of motion sickness will be understood. Although there are more sensitive indicators than vomiting, I believe that vomiting is the only part of the motion-sickness syndrome that is common to all the species which have motion sickness. Therefore, to attack the problem of motion sick- ness, you have to consider the element common to all the species, and that is vomiting. The autonomic effects that you mentioned, salivation and pallor, are normally controlled by the autonomic nervous system, but it has never been shown as far as I know that, in motion sickness, it is the autonomic nervous system which is effecting these changes. It might be, but it is just possible that the pallor, salivation, and sweating are caused by a circulating chemical that is not related to the autonomic transmitters. Lowenstein: Dr. Guedry placed emphasis on internal labyrinthine conflict. Why do many people show minimum disturbance in weightlessness when semicircular canal and missing otolith effect seem to contradict each other in weight- lessness; or is it that we have so far only tested people who are habituated? Guedry: Probably I should say I cannot answer your question. It seems to me that we are not exactly sure how that otolith system is responding during weightlessness. We may be stimulating the canals and otoliths with head movements, but the otoliths would be stimulated differently than in a 1-g environment. However, their sensory input would not necessarily be in direct conflict with that of the canals. If the astronauts were in a rotating vehicle, head movement near the axis of rotation would not necessarily produce conflict of the kind I pointed out between the otoliths and the canals. This also applies to a weightless situation which does not involve a rotating vehicle. If the otolith effect is simply missing as you suggest, then the axis of rotation signaled by the canals during head move- ments is not in direct conflict with any specific information from the otoliths. In the rotation situations to which I referred in our experiments, head movements produced di- rectional information from both the canals and the otoliths, and the directional information from these two sources was incompatible. However, we must also keep in mind that head movements during weightlessness do induce nausea in some individuals, as Billingham reported at the second symposium in 1966 (John Billingham: "Russian Experience of Problems on Vestibular Physiology Related to Space Environment," NASA SP-115, 1966, pp. 5-11). Waite: Dr. Money, would you care to postulate a function for the somasomatic synaptic connections between the vestibular nuclei and the dorsal vagal nucleus which have been described variously over the past few years, especially by Malcolm Carpenter? Money: No, I could not postulate a function; but, inasmuch as vagotomized dogs get sick as easily as most dogs. I do not think it is important for motion sickness. Barber: Can you speculate, Dr. Money, as to a phys- iological or perhaps phylogenetic purpose for motion sick- ness? There may be one, since it occurs in so many orders of life. Secondly, can you reconcile your views of chemical stimulation of the chemoreceptive emetic trigger zone to variations in susceptibility to motion sickness? Money: For whatever reason, there is individual varia- tion in susceptibility. If it is a matter of direct neuronal mechanism or connection, there would be a variation of that kind, or a variation in the rate at which an emetic chemical is produced or destroyed. Why some individuals would have such a mechanism and others a different one, I have no idea. The basic philosophical notion of motion sickness is something I have given some thought to and have come up with nothing. There seems to be no survival value in vom- iting in response to motion, and there is no survival value in becoming pale or sweating either. The only wild idea I had that was consistent with the fact is that it is just possible we had a sea-dwelling ancestor who did derive some sur- vival value from a vomiting response to motion such as in shallow water or something like that: and we just inherited this, and it is therefore a vestigial mechanism. But that is just a speculation.
66 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION Whiteside: My question, perhaps rather a comment, is directed to Dr. Guedry in regard to the conflict situation which he refers to in the vestibular labyrinth itself. I would have thought that there were indications that the conflict would have to be between different modalities, because although you can produce a conflict in the visual sense alone, for example, by the waterfall illusion, that situation does not produce nausea, certainly not in me, and I think not in any- one else, nor does it produce any discomfort of any nature. I would have thought, therefore, that the internal inter- modality concept was probably the better one. Guedry: This is something that we will not settle today; but, certainly without any visual input and with simply a few head movements in darkness, you can make people pretty sick fairly quickly. 1 would argue, and this is nothing but an argument, that the vestibular system gives vectorlike information. We are given directional information as well as magnitude information. The canals seem to locate the angular velocity vector relative to the skull. Now, if the canals respond only to angular acceleration, as is generally believed, then the canals cannot possibly locate the axis of rotation relative to gravity, but the otolith system certainly could. In the situations 1 described, the otolith system would indicate one axis of rotation relative to the skull, while the canals would indicate a different axis of rotation relative to the skull. The directions indicated would be incompatible. I do not want to say that is the only thing that produces motion sickness in all situations, but I think that an intra- labyrinthine conflict of this kind may be a primary cause of motion sickness in the situation to which I referred. Parker: Returning to the question of autonomic nervous system involvement in motion sickness, I would suggest that perhaps we can get at individual differences in sus- ceptibility to motion sickness by studying the autonomic responses. Autonomic-response characteristics may indi- cate individual predispositions to respond to stress in general and to motion-sickness-inducing stimuli in particular. If this approach is valid, why have autonomic nervous system response measurements not given us any information pre- viously? I think we are just beginning to get some under- standing, through the work of people who identify them- selves as psychophysiologists, of some properties of the autonomic nervous system. I think we are seeing three or four concepts which might be valuable for investigating individual differences in motion sickness. These concepts include the autonomic balance which has been explored by Wenger. He has suggested some relation to motion sickness with this measure and has developed quite precise measuring techniques. More interestingly, Lacey has developed a concept called response stereotypy; some people are very rigid in the man- ner in which they respond to various stresses, whereas other people are quite random in the kinds of autonomic responses they give, even to the same stress. Another concept might be autonomic precision. Here I refer to a sort of damping phenomenon. For example, you produce changes in heart rate as a function of exposure to a stress and, in some individuals, a great deal of rebound may be exhibited; i.e., they go from a high heart rate to well below their homeostatic level. We could suggest, perhaps, that individuals may be differentiated along a scale of pre- cision. We could suggest that they may be differentiated along a scale of stereotypy. We could suggest that indi- viduals may be differentiated along a scale of autonomic balance. By locating individuals within this hypothetical multifactor space, through appropriate testing, we might be able to predict some individual differences in motion sickness susceptibility. Torok: Autonomic nervous responses to strong vestibular stimulation have been known for a long time. There is not much doubt that such reactions exist. As to the meaning, the reason, or the philosophy of these reactions, they may be considered to be alarm reactions to extreme stimulation or abuse. The parasympathetic system particularly is known to serve and function in such capacity in general physiology. Autonomic responses do not occur during physiological stimulation, but will be manifest only when the stimulation strength is above physiological level or when the receptors are abused. Such a totally unphysiological abuse occurs during motion sickness. Dr. Money tries to prove that vomiting is not necessarily an autonomic nervous response in motion sickness. He speculates that it might be a direct vestibulomuscular response through intercostal nerve stimulations, for instance. Certainly, the intercostal musculature is involved along with the diaphragm and the abdominal muscles in vomiting, but these are rather secondary to the antiperistalsis which, in turn, is the autonomic effect elicited by vestibular abuse. This is not a unique phenomenon but rather the role of the autonomic nervous function in the entire general physiology. Money: 1 disagree that the autonomic nervous system is important to the vomiting of motion sickness. Perhaps Dr. Borison can outline the evidence for this, but it is a matter of controversy whether there is any antiperistalsis whatever in vomiting. Certainly, vomiting occurs quite normally in animals essentially lacking the autonomic nervous system altogether. This is not to say that the autonomic nervous system cannot be used as a valuable index of something that is going on somewhere else in the body; but nevertheless, except in frogs and fishes, antiperistalsis is dispensable for vomiting and it is not the essential thing. The essential force for expulsion in mammals comes from the respiratory musculature and the abdominal-wall musculature. Per- haps we could submit this to Dr. Borison for mediation.
SESSION III Chairman: THOMAS C. D. WHITESIDE R.A.F. Institute of Aviation Medicine Farnborough, England