Symposium on the Role of the Vestibular Organs in Space Exploration (1970)

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The Semicircular Canals as a Primary Etiological Factor in Motion Sickness1 EARL F. MILLER II AND ASHTON GRAYBIEL Naval Aerospace Medical Institute SUMMARY Data are presented which support the view that the semicircular canals can act as the essential factor for the production of motion sickness and the evocation of symptoms characteristic of this malady in the absence of "motion." Quantitative grading of acute symptoms demonstrated that motion sickness can be evoked by stimuli which are at once adequately provocative and unique for the canals. These results are compared with those of two provocative tests that introduce Coriolis forces and with one that generates a rotating linear acceleration vector when human subjects are exposed in rotating devices. Wide interindividual differences but only slight intraindividual differences among the six provocative test conditions are revealed. The pattern of symptoms manifested by the group of 10 subjects at the test endpoint. moderate malaise, is also similar among these tests. The fact that typical symptoms of motion sickness (M IIA endpoint) were produced by bithermal irrigation as well as simple angular acceleration in several subjects representing a wide range of susceptibility adds to the evidence that the semicircular canals can act as the primary etiological factor in this malady. INTRODUCTION This report is intended to complement the preceding one by centering attention on the in- dividual role of the semicircular canals in the etiology of motion sickness. The presentation falls into two main parts, the first demonstrating the essentiality of the canals and the second comparing susceptibility to symptoms charac- teristic of motion sickness in the same subjects when the canals only, the otoliths primarily, and when both organs of equilibrium are stimulated simultaneously. Some evidence that the canals are the primary etiological factor in motion sickness has been 'This study was supported by Contract T-81633, Bio- medieal Research Office, Manned Spacecraft Center, and by Order R-93, Office of Advanced Research and Tech- nology, NASA. furnished by animal and human studies. Money and Friedberg (ref. 1) reported that confirmed inactivation of all six semicircular canals by plugging eliminates motion sickness in suscep- tible dogs, at least to the same extent as does bilateral labyrinthectomy of these animals. None of four patients treated for Meniere's disease with streptomycin sulfate experienced the nausea syndrome while carrying out the Dial test or during exercises to habituate them to the oculogyral illusion (ref. 2). The vestilm- lometric testing of these individuals revealed great suppression of semicircular canal function, but sparing of various amounts of otolith func- tion. In two patients this was within normal range, although there was a probability that some loss of otolith function had nevertheless oc- curred. The history of motion sickness was not helpful; these patients had not experienced 6')

70 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION much motion sickness prior to the therapy, but, on the other hand, none had been exposed to very stressful force environments. Still the argument that motion sickness cannot occur without at least some residual function of the semicircular canals remains unchallenged. Historically, several investigators have dem- onstrated, for the most part in an incidental manner, that specific stimulation of the canals by caloric irrigation and simple angular accel- eration can evoke vegetative reactions in man. Schmiedekam and Hensen as early as 1868 (ref. 3) recorded that filling the external auditory canal with cold water produced dizziness, nausea, and vomiting, whereas water of near body temperature did not have this effect. Calori- zation has been employed by several investi- gators for determining motion sickness suscepti- bility (refs. 4 to 7). Barany (ref. 8) reported that his now classical clinical method of evoking nystagmus by rotating a patient 10 times in approximately 20 seconds, then suddenly stopping him, only infrequently provoked nausea. "Impulse" braking of lesser intensity used for example in certain cupulo- metric techniques can also evoke vegetative reactions (refs. 5 and 9), but this response would only be expected in individuals with fairly high susceptibility. Increasing the rate of angular acceleration, as was done in the present study, markedly increases the incidence of motion sickness and thus its adequacy as a test of sus- ceptibility for general use. Rates within or above the range of this study have been employed in cupulometric studies but not repeatedly for the purpose of studying susceptibility. These ob- servations illustrate that if a provocative type of motion is used as the stimulus, its effect in terms of motion-sickness production is dependent upon the strength of the forces involved, within defi- nite limits and, of course, the level of the sub- ject's susceptibility. The selection of an ade- quately provocative type of motion from among the wide variety available to the investigator who desires to develop a laboratory test of motion- sickness susceptibility is quite another matter. In most cases this process is either based upon information gained from "natural" environ- ments or empiric data, since the major factor is not the vestibular stimulus intensity but its pattern whose effectiveness is difficult to predict (ref. 10). For example, relatively small forces which, with a particular patterning may be well tolerated in one situation, with another, may be surprisingly provocative. Recently it has been shown that even ordinary head movements in near weightlessness can produce motion sickness (ref. 11). Complex temporal and spatial patterns of vestibular stimulation can be generated by active or passive movement of the subject's head while he is being rotated at a constant velocity. This procedure has been shown by numerous investigators to be highly provocative, even at low rotational rates (refs. 12 to 15), but unlike the two general methods of canalicular stimu- lation already described, it provides otolithic stimulation as well. PROCEDURE Subjects The subjects used in the intertest compari- sons were ten young Navy enlisted males, 19 or 20 years of age. Each had passed the standard medical examination required by the Navy De- partment and was in excellent health at the time of these tests. In addition, each manifested normal vestibular function as determined by specific tests of otolithic (refs. 16 and 17) and semicircular canal function (ref. 18). The addi- tional subjects cited in this report have been described in other communications (preceding paper, this symposium, entitled "The Otolith Organs as a Primary Etiological Factor in Mo- tion Sickness: With a Note on 'Off-Vertical' Rotation," by Graybiel and Miller: ref. 13; and Miller and Graybiel, unpublished data). Methods In each of the tests herein described, the vestibular stressor level was adjusted so that it was subjectively and objectively equivalent among all subjects as indicated by the common manifestation of a definitive level of moderate (M HA) or severe (M III) malaise (ref. 19). The M IIA and M III endpoints as well as other diagnostic malaise levels were quantitatively determined by specific diagnostic criteria which

SEMICIRCULAR CANALS AS A FACTOR IN MOTION SICKNESS 71 are outlined in table 1. This set of ground rules has placed the study of motion sickness in this laboratory on a highly workable, standardized, and quantitative basis. Moreover, it has per- mitted the reliable measurement of susceptibility using premonitory signs and symptoms without resorting to the classical pathognomonic endpoint of vomiting or retching. In fact, in this investi- gation as well as in others currently being con- ducted, M IIA, a condition in which even mild nausea is a rare occurrence, served success- fully in defining susceptibility (E. F. Miller II and A. Graybiel, "Comparison of Five Levels of Motion Sickness Severity as the Basis for Grading Susceptibility," in preparation). A tally sheet (shown as an appendix) was used to score the specific signs and symptoms of motion sickness as they appeared in each test; this aid permits even an observer with minimal training to record the symptomatology, sum corresponding point values, and end the provocative stimulation upon reaching the desired criterion (ref. 13). The order of testing varied among the sub- jects as listed in table 2; the time interval between tests of an individual was at least 24 hours. The first two methods to be described were experimental probes; the others are used routinely in this laboratory. Angular Acceleration Susceptibility (AAS) Test The subject was rigidly fixed in an upright posi- tion with his head and neck held firmly by a fiber- glass mold and centered approximately over the axis of rotation of a special motor-driven Barany- type chair. The subject's eyes were open and un- covered. The test was initiated (time zero) by rapidly accelerating the chair within approxi- mately 4 seconds (~ 90°/sec2) to a velocity of 30 or 60 rpm which was maintained until 150 seconds had elapsed. The choice of maximum chair velocity was dependent upon the sub- ject's level of susceptibility. It was found that the more susceptible individuals could not sustain the initial acceleration to 60 rpm without mani- festing very rapidly appearing and severe symp- toms; these individuals were retested at 30 rpm (~ 45°/sec2) (table 2). Following the constant- velocity phase, the chair was decelerated to a stop within approximately 4 seconds. The chair remained stationary until the accumulative time totaled 300 seconds; this inactive phase was TABLE I. —Diagnastic Categorization of Different Levels of Severity of Acute Motion Sickness Category Pathognomonic, Major, 8 points Minor, 4 points Minimal, 2 points AQS,2 1 point 16 points Nausea syndrome Vomiting or Nausea II III ; N .1 • Skin retching. Pallor III Pallor II discomfort. Pallor I awareness. Cold sweating III II I warmth * II. Increased salivation Ill II.. I Drowsiness Ill II I Pain Central nervous system ... Eyes closed, * II. Eyes open. III. Frank sickness (S) * 16 points Severe malaise (M III) 8-15 points Moderate malaise A (M IIA) 5-7 points Moderate malaise B Slight malaise (MI) 1-2 points (M Illii 3^-4 points Levels of Severity Identified by Total Points Scored 1 From ref. 19. 2 Additional qualifying symptoms. 3 III, severe or marked; II, moderate; I, slight.

72 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION introduced to allow for any lag in the appearance or intensification of the diagnostic symptoms. The 300-second procedural cycle (acceleration, constant velocity; deceleration, static hold) was repeated up to 20 times or until the subject exhibited M IIA. If the test were terminated during a dynamic procedural phase, the chair was slowly decelerated (0.5°/sec2) to a stop. The accumulative test duration served as the index of susceptibility to motion which involved simple angular acceleration without any significant gravitoinertial force changes. Concern has been expressed that rates near or above those provided by the Barany method can damage the labyrinths (ref. 20). Arslan argued that such accelerations which can be greatly exceeded in ordinary head movements probably do not harm the cupula (ref. 21) and suggested the possibility of central adaptation in the decrease in the duration of nystagmus and sensation of rotation. There was no op- portunity in the present study to test the after- effects, if any, of the multiple exposures to rapid angular acceleration in the AAS test which with the exception of one subject was the final one administered. Such a possibility should be carefully explored before this method is em- ployed routinely. Bithermal Irrigation Susceptibility (BIS) Test By strict definition, any test employing caloric irrigation does not, at least in any direct way, measure motion-sickness susceptibility since the subject remains stationary. However, cupular deflection is accomplished, and the effect in terms of subjective sensations and attendant symptoms closely resembles that which can be induced by accelerative forces. A version of the Fitzgerald-Hallpike method (ref. 22) has been used as a provocative test. It has also been our experience that the stimulus conditions of this particular test are occasionally sufficient to elicit symptoms to the point of in- validating any subsequent test of susceptibility made on the same day. To increase its provoca- tive effect for more subjects, we irrigated both ears simultaneously, one at the higher, the other at the lower temperature level. In this test the subject was seated upright in a stationary chair with his head firmly secured by straps and a head rest. He was instructed in the use of hand sig- nals which the experimenter used to question TABLE 2.—Motion-Sickness Susceptibility as Measured by the 6 Experimental Conditions Angular Bithermal Bithermal Coriolis Coriolis accel- Off-vertical acceleration irrigation. irrigation. acceleration, eration, slow rotation c u- je eyes open eyes closed rotating chair rotation room Test Score, Score, Score, Score, Score, Score, order Rank time/RPM. Rank time, Rank time. Rank CSS1 Rank RPM/HM ' Rank time, sec sec sec sec SY 21 41/30 1 26 1 35 1 1.9 1 7.5/20 3 620 4—5-6-2-3-1 JE 2 240/30 6 156 2 89 7 9.0 9.5 20.0/40 1 325 4—5—6—2-3-1 JA 3 340/30 5 134 9 315 2 6.4 3 7.5/35 5 1280 5-^-6-2-3-1 95/60 HR 4 180/60 3 119 3 115 4 7.4 2 7.5/30 6 1755 5-4-2-6-3-1 HB 5 460/30 4 124 4 130 3 6.8 4 10.0/30 4 970 4-5-6—2-3-1 185/60 HE 6 187/60 8 180 6 200 8 9.4 7 15.0/30 7 1790 5-6—2—4-3-1 RO 7 374/60 9.5 360 + 10 360 + 5.5 8.2 5.5 10.0/50 2 550 4—5-6—1-3-2 HU 8 420/60 2 105 5 180 5.5 8.2 5.5 10.0/50 8 2075 5-6-^4-2-3-1 DA 9 605/60 7 172 8 295 9.5 24.0 9.5 20.0/40 10 3720 4-5—6-3-2-1 DI 10 1080/60 9.5 360 + 7 207 9.5 24.0 8 15.0/45 9 3675 4—5-6—3—2-1 1 Head movements. 2 Most susceptible.

SEMICIRCULAR CANALS AS A FACTOR IN MOTION SICKNESS 73 the occurrence of specific diagnostic symptoms during the binaural irrigation. The test was initiated with the simultaneous introduction of a stream of warm water (44° C) into the right and cold water (30° C) into the left external auditory canal. A constant flow rate of 6 cc/sec into each ear was maintained until acute signs and symptoms indicated M IIA or an arbitrary time limit of 6 minutes was reached. The water temperature was maintained within ±0.1° C of the stated values. The procedure was varied by either having the subject's eyes closed (BIS E/C) or eyes open (BIS E/O), conditions which will also be described in the following text by eyes covered or eyes uncovered, respec- tively. The duration of the irrigation period in seconds served as a convenient index of motion- sickness susceptibility as measured by this method. Coriolis Acceleration Susceptibility (CAS) Test Chair The experimental apparatus (Stille rotational chair) and procedure for a standardized and highly reliable laboratory test of susceptibility to Coriolis forces are diagramed in figure 1 and described in detail in another report (ref. 13). It was found early in this test's developmental program that one rate of rotation could not be used to scale the wide range of individual dif- ferences in this susceptibility, and chair velocity had to be introduced as an additional parameter. The stressor effect of a standard head tilt as a function of chair velocity was measured in an- other study (Miller and Graybiel, unpublished data) by determining among several subjects the number of head tilts required to elicit a common malaise level (M IIA and M HI) at each of sev- eral different chair velocities. Individually, the regularity of this function was limited to rota- tional rates above a critical amount. When the rpm was reduced below this amount, there was characteristically a sudden marked increase in the subject's capacity for making head move- ments without evoking symptoms, as would be predicted from the results of testing at higher velocities. These findings indicated the pos- sible influence and the limits of physiological mechanisms for adjusting to motion stress which are expressed as the individual's functional vestibular reserve (FVR) (ref. 23). One inter- pretation of the critical FVR value is that it rep- resents a limit of an individual's ability to make homeostatic adjustments, perhaps in the form of inhibiting irradiation of vestibular activity to neural centers involved in the genesis of motion sickness. If the chair rpm were lower than indi- cated for the individual's FVR, neurovegetative symptoms apparently would not appear no mat- ter how long this test were continued. The con- cept of FVR is of great practical significance in training and habituating astronauts for space flight (ref. 23), but in this and other tests of sus- ceptibility it is important that the vestibular stressor level be in excess of the subject's FVR UPRIGHT POSITIOM FIGURE 1. —Diagram of the standardized procedure for making each sequence of head movements to and from tilt positions I through 5 during clockwise and counterclockwise rotation of the chair.

74 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION in order to obtain a valid calibration of his susceptibility. Attention was given in the design of this test to factors which reduce or, if possible, eliminate habituation. Moving the head in different direc- tions for a limited number of times, covering the eyes, and if the test were repeated, reversing the direction of rotation (CW, CCW) were pro- cedures introduced to increase the complexity of the stimulus, to decrease experiential factors and thereby reduce the subject's ability to habitu- ate to the test conditions. Furthermore, a chair velocity which would stress the individual at a level above his functional vestibular reserve was carefully selected. These procedures prob- ably contributed to its high test-retest reliability (refs. 11 and 13). The subject was secured in the rotary chair and blindfolded. While stationary, he demonstrated the head-movement sequence. After the sub- ject returned to an upright position, the chair was rotated clockwise or counterclockwise at an acceleration rate of 5°/sec2 until one of the several programed constant velocities (2.5, 5.0, 7.5, 10.0, 12.5, 15.0, 20.0,25.0, 30.0 rpm) was reached. At no less than 60 seconds thereafter, the first head movement sequence was begun. Coriolis accel- eration was then introduced by having the sub- ject bend his neck and upper body as necessary to effect approximately 90° positive and negative movements of his head (and vestibular apparatus) from its upright position within the frontal and sagittal planes according to the following pattern: forward, upright, pause; rightward, upright, pause; backward, upright, pause; leftward, up- right, pause; forward, upright, rest (fig. 1). Each of the movements to a new position or the return to upright was executed smoothly over a 1- second period. A taped recording directed and standardized the temporal sequence of head movements. The pauses between movements were of the same (1-second) duration with the final pause (rest) lasting for 20 seconds. The rest duration was found to be short enough so that any appreci- able recovery from previous stimulation did not occur. On the other hand, it was sufficiently long to query the subject fully and to observe closely for signs of malaise appearing on his face as well as to allow for the lag in the appearance of motion-sickness symptoms after each exposure to the head movement sequence. Immediately upon reaching the M IIA level the head move- ments were terminated, the subject returned to his upright position, and the chair was slowly decelerated (0.5°/sec2) to a stop. The level of motion stress imposed upon each subject had to be such that his symptoms would develop rather gradually in order that the ob- server could readily differentiate and sequentially register them; furthermore, it was of great prac- tical importance to avoid overstimulating the subject to the point of extreme nausea or vomiting (frank sickness). For this reason, the "motion experience questionnaire" was developed as a guide for selecting the proper chair rotational rate for testing each subject (ref. 13). Table 3 lists the best estimate of the chair's rotational test rate (rpm) which we so far have been able to gain from the average level of experience X and intensity of symptoms S which the subject reports in this questionnaire. The table's usefulness is demonstrated by the fact that, in approximately 4 out of 5 cases among 250 subjects, it predicted an rpm which yielded the malaise criterion within the limits of 40 to 166 head movements on the first trial (ref. 13). Only one additional test was usually necessary to calibrate those individuals who were tested with an incorrect rotational rate. It is our experience that when M IIA or M III occurs within a limited range of head movements (ref. 13), the signs and symptoms develop regularly and gradually without exceeding the chosen criterion level. If the number of head movements required falls outside this range, the test is considered invalid, and the subject is retested after at least 48 hours have elapsed, with the rpm adjusted in accordance with his initial response. If the M IIA criterion is not reached at this limit of 150 head movements when 30 rpm is used, the test is stopped and the results used as evidence that the individual was essen- tially immune to motion sickness. With regard to the physical forces present, the amount of Coriolis stimulation with the set pattern of head movements was found to vary directly with the rotational rate of the chair (Miller and Graybiel, unpublished data). The average

SEMICIRCULAR CANALS AS A FACTOR IN MOTION SICKNESS 75 TABLE 3. — Table of Rotary Chair Test Velocities Found To Be Most Often Associated With the Various Average Coded Experience X and Symptoms S Levels Reported in the Motion Experience Questionnaire M III Symptoms S 0,0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Experience X: 0.5 '10.0 12.5 12.5 12.5 12.5 15.0 20.0 25.0 30.0 30.0 10.0 12.5 12.5 12.5 12.5 15.0 15.0 20.0 25.0 30.0 10.0 10.0 12.5 12.5 12.5 12.5 15.0 15.0 20.0 25.0 10.0 10.0 10.0 12.5 12.5 12.5 15.0 15.0 20.0 25.0 10.0 10.0 10.0 12.5 12.5 12.5 12.5 15.0 20.0 25.0 10.0 10.0 10.0 10.0 12.5 12.5 12.5 15.0 15.0 20.0 10.0 10.0 10.0 10.0 12.5 12.5 12.5 12.5 15.0 15.0 7.5 7.5 7.5 10.0 10.0 12.5 12.5 12.5 12.5 12.5 5.0 5.0 7.5 7.5 7.5 10.0 10.0 10.0 10.0 10.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 7.5 7.5 7.5 7.5 7.5 1.0 1.5 2.0 2.5 5.0 7.5 7.5 7.5 7.5 7.5 3.0 3.5 4.0 4.5 5.0 1 Rotary chair velocity (rpm). stressor effect (f-factor) of a single head move- ment which was determined for each of the test velocities and malaise criteria (IIA and III) is presented in table 4 (Miller and Graybiel, unpub- lished data). With these values a measure of each individual's susceptibility, referred to as his Coriolis Sickness Susceptibility Index or CSSI, is simply calculated by multiplying the ap- propriate f-factor associated with the chair's test velocity and malaise criterion by the number of head movements N required to elicit the selected malaise criterion: TABLE 4. — Average Stressor Effect (E-Factor) of a Single Head Movement for Each of the Test Velocities and Malaise IIA and III Criteria Slow Rotation Room The dial test conducted on the Pensacola Slow Rotation Room (SRR) has been described else- where (ref. 14). Essentially, it involves dials which are positioned around the subject such that he is forced to make head movements, which are out of the plane of the slowly rotating room, when resetting these dials according to taped instruc- tions. Twenty sequences of five head move- ments are made in a single successive series of trials at 5.0, 7.5, 10.0, 15.0, 20.0 rpm or until M III develops. Unlike the other tests, the patterning and progressive buildup of symptoms up to this endpoint were not recorded and therefore could not be compared. The test results are expressed in terms of the number of head movements executed at the rpm level which produced M III. Test velocity, rpm MI1A' M III 2 30.0 0.67 0.60 250 48 43 200. 33 28 15.0 205 165 12 5 150 118 10.0 .105 .078 7 5 (Vvl ftd/» 50 032 021 25 010 006 1 0 002 001 1 150 head movements at 30 rpm= 100.0. 166 head movements at 30 rpm = 100.0. Off-Vertical Rotation (OVR) Susceptibility Test This method was described in the preceding report (this symposium, Graybiel and Miller). The subject sat upright in a Stille rotary chair and his eyes were covered with a padded shield. The chair was tilted so that its rotational axis was displaced 10 degrees from the gravitational vertical (fig. 2), then accelerated slowly (0.5°/ sec2) for 30 seconds to reach and maintain for a period of 6 minutes the constant velocity of 2.5 rpm. Continuing from this velocity level, the same sequence of slow acceleration, followed by 6 minutes of constant velocity, was repeated in

76 THE ROLE OF THE VEST1BULAR ORGANS IN SPACE EXPLORATION FIGURE 2. — Diagmm of apparatus used in the off-vertical rotation test. succession for levels of 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, and 25.0 rpm. With the onset of M IIA the chair was quickly returned to its up- right position, which ended all provocative stim- ulation, and then the rotation was slowly (0.5°/ sec2) halted. RESULTS AND DISCUSSION The results are summarized in table 2 which lists each subject's score expressed in terms of magnitude of the stimulus and duration of its application and corresponding rank order of motion-sickness susceptibility as determined with each of the test procedures. As indicated in the table, the vestibular stimuli associated with each test were adequate to provoke M IIA (M III, for the dial test) in all subjects except RO and DI with eyes covered, and RO with eyes open during the bithermal irrigation test. Intratest Subject Differences All tests yielded a wide range of scores in- dicating that susceptibility varied considerably among the subjects. For example, susceptibility as measured by the angular acceleration test ranged from 41 seconds at 30 rpm to 1080 seconds at 60 rpm. All of the subjects tested at 30 rpm ranked below those tested at 60 rpm. since the effective stimulus ratio as indicated by the dual test results of two subjects (table 2) greatly exceeded the 2:1 ratio based upon chair velocities. In the bithermal irrigation tests, subject RO experienced only mild symptoms with 6 minutes of irrigation, whereas subject S\ developed M IIA after only 26 seconds of irrigation: the rapid development and continuation in the build- up of his symptoms after M IIA was reached and irrigation stopped required several trials each on a separate day in which the duration of irrigation was progressively reduced in order to determine this threshold. The substantial lag between the caloric stimulus and the manifestation of symp- toms was also revealed but to a lesser extent in the other subjects. As a result, the endpoint could not always be properly controlled and often exceeded the M IIA level, sometimes reaching severe malaise (M III). For this reason, the test protocol has been changed for future studies to include pauses in the irrigation throughout the test. Susceptibility to Coriolis forces generated by active head movements in a rotating chair covered a wide range from what could be de- scribed as high (CSSI=1.9) to moderate (CSSI = 24.0). This gross classification on an arbitrary scale of 0 to 100 is based upon data of a previous study (ref. 13) (fig. 3) which revealed marked skewness toward the high score (low suscepti- bility) end of the frequency distribution of Coriolis sickness susceptibility among 250 subjects. This graphic representation, the first to be ex- pressed quantitatively on a single scale of values, indicates that the distribution of motion-sickness susceptibility is not Gaussian as has been sug- gested (ref. 24). Under the dial test conditions, development of M III was well distributed throughout the range of scores from 20 head movements at 7.5 rpm (sub- ject SY) to 40 head movements at 20 rpm (subjects JE, DA). Susceptibility to simple rotation around an off- vertical axis varied about tenfold in terms of dura- tion of exposure and terminal velocity level; viz, from 325 seconds, 2.5 rpm (subject JE) to 3720 seconds, 25 rpm (subject DA).

SEMICIRCULAR CANALS AS A FACTOR IN MOTION SICKNESS 77 JO 40 907? NX FlciiRE 3. — Distribution of Coriolis sickness suscepubility index (CSS/) among 250 normal subjects. Intertest Subject Differences In addition to intratest individual differences, certain subjects did not always maintain their rank order among the several test conditions. Since the test sequence varied among subjects and each test was administered only once, no im- portance can be attached to small intraindividual differences in scores or rank order. However, some differences are so substantial that it must be. considered that susceptibility may vary as a function of the type of vestibular stimulus and this variance in turn may be highly individualistic. For example, subject JE, who revealed high sus- ceptibility to angular acceleration and off-vertical rotation, was relatively unsusceptible to Coriolis forces encountered in the slow rotation room as well as in the rotating chair. The most ap- parent difference between the conditions of these two types of tests was the active or passive movements of the head in space which in this individual could have been the significant factor. Another example, subject RO, the least susceptible to bithermal bilabyrinthine caloriza- tion, ranked second in susceptibility to off-vertical rotation. As a general rule, however, susceptibility to the various provocative tests followed a more or less regular order. The extent of this orderli- ness is expressed in the correlations among sus- ceptibility rankings for the six provocative test conditions as presented in table 5. All correla- tions were positive in sign and substantial in amount; the highest (p = 0.93) was found between Coriolis susceptibility as measured by the rotating chair and the rotating room methods. This find- ing can be explained by the fact that the Coriolis forces used as the stimulus in these two situations were quite similar. Differences in the two pro- cedures which were principally vision versus no vision, on-axis versus off-axis rotation evidently did not differentially affect the subjects' relative susceptibility. The high correlation indicates that the standardized rotating chair test (ref. 13) can be used as a valid substitute for the dial test when a centrifuge is not available. Furthermore, the data collected with the dial test (refs. 14 and 25) can serve as background for the new test. The next highest correlation (0.75) existed be- tween susceptibility as measured by bithermal TABLE 5.— Correlations Among Susceptibility as Ranked by Several Tests of Motion Sickness Upright angular acceleration without head movements, eyes closed (AAS) Upright bithermal irrigation, eyes closed, no movement (BIS E/C) Upright bithermal irrigation, eyes open, no movement (BIS E/O) Upright constant on-axis rotation with active head movements, eyes closed (CAS, chair) Upright constant off-axis rotation with active head movements, eyes open (CAS, SRR) Tilted off-vertical rotation, passive head movements, eyes closed (OVR) HAS 0 60 057 0 71 0 56 0.75 BIS E/f 69 33 31 32 BIS E/O .75 .74 .19 93 .55 CAS SRR 35 OVR

78 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION irrigation (eyes open) and that measured with Coriolis force environments of the dial and rotary chair tests. Correlations between each of the Coriolis acceleration tests and the bithermal irri- gation test dropped markedly (p = 0.31 and 0.33) when the eyes were covered during irrigations, reflecting to a great extent the rank order differ- ence of subject J A as already described. An equally high correlation was found between angular acceleration and off-vertical rotation sus- ceptibility measurements, while the latter corre- lated the least (0.19) with the bithermal irrigation test (eyes open) data. One significant differ- ence which exists among these tests and bither- mal irrigation tests probably lies in the presence or absence of motion which is also perceived by nonlabyrinthine receptors, a secondary factor in motion sickness. This might also explain the finding of only moderate (0.57 and 0.60) correla- tions between the two "pure" tests of suscepti- bility to semicircular canal stimulation. It must also be considered that the calorization technique stimulated mainly the vertical, whereas the angu- lar acceleration stimulated mainly the lateral canals which may have had a differential in- fluence upon susceptibility. The moderately high correlation between the eyes covered and uncovered conditions of the bithermal irriga- tion test indicates that visual cues generally had no appreciable effect upon the susceptibility of most subjects, but there were exceptions. A greater effect from irrigation was found with vision for subject JA and without for subjects JE and DI. Subject DI who experienced only mild dizziness during the 6 minutes of irrigation when he observed the laboratory environment, on the other hand, spontaneously noted and complained of the great increase in sensations and symptoms without vision, and he developed M IIA after 207 seconds. Subject JA, who ranked fifth in sus- ceptibility with visual stimuli present, sustained greater than twice the duration of irrigation and ranked ninth without this influence. These results suggest that visual stimuli may in certain individuals tend either to suppress (ref. 15) or facilitate the effects of vestibular activity and indi- cate the complexity and variability in processing multiple sensory inputs. Since the subject's head was rigidly fixed in these studies, vision would ap- pear to be a secondary but significant factor in motion sickness whose influence goes consider- ably beyond any aid it may provide for immobili- zation of the head in situations in which it is not restrained (ref. 26). The substantial correlations found among all the various provocative tests of this study indicate that generally individuals possess an overall sus- ceptibility to motion sickness which is relatively independent of the type of motion. However, it is well known and shown in this study that suscepti- bility measured in one motion environment may not always be a valid predictor of susceptibility in another (refs. 14 and 25). Other factors, includ- ing otolithic contributions which have been dra- matically demonstrated when the normal g-load is counteracted (ref. 11), may markedly influence susceptibility. The general agreement, but occasional wide discrepancy, between susceptibility to different motion environments is exemplified in the results shown in figure 4 which were obtained from a larger population tested by the Coriolis (rotary chair) and the off-vertical rotation methods. These two sets of data collected on 35 of 66 nor- t- a. IT UJ bj U N-35 HIGH- -SUSCEPTIBILITY RANK • -»-LOW CORIOLIS ACCELERATION FIGURE b.—Scattergram of .15 normal subjects showing the relationship between motion-sickness-susceptibility test by the Coriolis (rotary chair) and off-vertical rotation tests.

SEMICIRCULAR CANALS AS A FACTOR IN MOTION SICKNESS 79 mal subjects, described in the preceding study (this symposium, Graybiel and Miller), correlate highly and at a level comparable to that reported for the smaller group of subjects of this study (table 5). Most cases fall at or near the regres- sion line but there are notable exceptions, par- ticularly those individuals denoted by letters A, B, and C in figure 4. In this small percentage of subjects, the factor of active or passive movement of the vestibular organs might have been in- fluential, but the relative amounts of stimulation of the canals and otoliths in the two test situa- tions must also be considered. In most cases, however, the two methods of measuring suscep- tibility yield quite similar results. Symptomatology The subjects' M IIAsymptomatological pattern- ing found for the angular acceleration, Coriolis acceleration, the two bithermal irrigations, and off-vertical rotation conditions is summarized in figure 5. The patterning among these tests was similar with respect to frequency of incidence and grouping of symptoms, but some significant differences were revealed. Pallor and epigastric awareness or discomfort were the most significant symptoms for all provocative tests. Headache II, III, and nausea I were manifested infrequently at this endpoint level. Drowsiness I occurred most frequently (3 of the 10 subjects) during off-vertical rotation. Increased subjective warmth was ex- perienced more frequently in the Coriolis test which required active head and body movements and thereby may have contributed to the mani- festation of this symptom; this test provoked in- creased salivation in only one subject. Cold sweating was conspicuously absent in the off- vertical rotation and the angular acceleration tests which, on the other hand, featured increased salivation. Caloric irrigation elicited moderate to severe dizziness in about one-half the subjects. The similarities among the group's symptom- atological patterns would be an indication that similar physiological mechanisms were involved. Comparison of symptomatology manifested by the group of 35 subjects during passive off-vertical rotation and active head movements with vertical rotation revealed that with the exception of the difference in subjective warmth, again influenced by exercise, no distinct differences were found (fig. 6). With respect to rate of buildup of symptoms, there was a clear-cut difference between the off-vertical rotation and the Coriolis acceleration test which probably stems from a procedural difference. When the standardized test of susceptibility for Coriolis acceleration is properly CORIOLIS ACCELERATION OFF-VERTICAL ROTATION FIGURE 5. — Frequency of specific diagnostic symptoms manifested for each test condition. FIGURE 6. —Comparison of frequency of specific diagnostic symptoms manifested during off-vertical (10°) and vertical (with active head movements) rotations.

80 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION conducted, symptoms slowly appear and increase in intensity from M I up to the endpoint (fig. 7); whereas, in the case of off-vertical rotation they can appear suddenly and wax rapidly, passing through several malaise levels within several seconds' time (fig. 6, preceding paper this symposium, Graybiel and Miller). Much greater care and closer observation are therefore re- quired in administering this test in order to avoid overshooting the selected malaise criterion. It is probable that exposure to longer durations at a velocity below the terminal one would be suf- ficiently provocative yet yield a slower symptom buildup pattern. Among 250 subjects of a previous study (ref. 13), nausea I, epigastric discomfort, or epigastric awareness was the predominant feature of severe malaise (M III). However, a significant propor- tion of this test population (9.6 percent) failed to manifest even the mildest form of this syndrome at this malaise level. This finding is not in aline- ment with the classical viewpoint which, for the most part, equates motion sickness with a gastro- intestinal reaction marked by nausea or vomiting, symptoms which have represented the endpoint in the vast majority of studies dealing with this topic and are still regarded by some investigators as the only ones having reliability (ref. 24). If M III as diagnosed by a nonnausea symptom complex is equivalent, in terms of the subject's well-being, his psychomotor efficiency, or some other indicator, to that involving the nausea syndrome, then the restricted "nausea syndrome" criterion of motion sickness must be reevaluated. In many of the cases in which the endpoint was reached without the nausea syndrome, the symptoms were for the most part effectively localized in the head region; e.g., moderate or severe levels of drowsiness to the point of being unable to follow instructions, headache, facial pallor, severe dizziness, and increased salivation. It is possible if not probable that if the motion stress had been continued, the nausea syndrome would have eventually appeared in most of these subjects. In any case it is questionable that the manifestation of the nausea syndrome is required for predicting susceptibility to frank motion sickness. As described in the methods section, the average relative stimulus effect of a single •/r . • T"^300 FIcURE 1.-Variations among six selected cases (subjects A through f) in the buildup rate of Coriolis-sickness symptoms. head movement in the Coriolis acceleration (rotarv chair) test could be expressed by the factor E. which directly related in logarithmic terms to chair velocity (table 4). It appears, therefore, when vestibular stressor conditions are appropriate, each head movement may act to release autonomic effects on an incremental and accumulative basis through a neural or humoral mechanism. The latter is suggested in the report of Wang and Chinn that insertion of plastic barriers in the fourth ventricle of several dogs removed their susceptibility even though their emetic thresholds to apomorphine were not raised (ref. 27). In any case the rate of release seems dependent on the stressor "step-size" taken with each head movement at a specific chair velocity. Six cases from a 250-subjecl group (A. B, C, D, E, F, fig. 7) illustrate the different rates in the buildup of symptoms. The ideal pattern of response is illustrated by cases D and E. As a rule, when a subject experienced M IIA and M III with only a few head movements (cases A, B, C) it was found extremely difficult if not impossible at times to prevent a sky- rocketing of his symptoms up to the level of frank sickness (FS) as illustrated by cases A and B. These two cases show the typical response when the rpm is too high relative to their susceptibility level. If. on the other hand, the rpm selected is too low for the individual, head movements can be continued beyond a practical number

SEMICIRCULAR CANALS AS A FACTOR IN MOTION SICKNESS 81 without any apparent effect, such as in case F in figure 7. In another case, not represented in the figure, in which the subject was rotated below his critical rpm value, 900 head movements were executed without provoking any increase in symptoms beyond that found in the initial head movements. In fact, there was a lessening and disappearance of his symptoms as the test progressed. However, when each of these subjects was retested at a properly adjusted rpm, the "normal" pattern of response (such as cases D and E) resulted. In these studies the intensity and duration of the vestibular stimulus were individually con- trolled so as to provide an equivalent stressor stimulus in terms of the response of each subject under each test condition as diagnosed by specific criteria (ref. 19). The physical dimensions of the stimulus therefore varied with the individual but in most cases they were small, approaching what commonly is regarded as physiological proportions, yet they proved highly effective in provoking motion sickness. As expressed by Lansberg (ref. 28), the opinion advanced by certain investigators (refs. 29 to 32) that motion sickness is simply the result of overstimulation of the otolith organs is untenable. APPENDIX Svmptom Irvel 1't. val. PriiK-ipal symptoms RPM i:w i:i:»' TMP, nix. HAC, DRS, _PJj SWT, r'AL. SALI+): NSA. Major 8 1tt Ill III II. Ill Minor 4 II II II 1 llllRlll.A 'lll Minimal 2 I J 1 1 E.I)., AQS 1 IL Ill n. in u. in | E.A.,- Othrrs>m. HM,, 5 10 IS 20 25 30 I 35 40 45 SO 55 i 60 — 70 75 • L 80 i 85 l 90 1 05 u. |100 1. Subjrctivr warmth 2. DizziiM"* 3. HraiIafhr 4. Druwsiness 5. ('.old sweating 6. Pallor 7. Salivation inrrt- 8. NauM-a 9. Epigastric di(u-omfim 10. Kpipastric awarenes» I I. Hfail •(!•.•> <:•,. n.

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