Torsional vestibulo-ocular reflex measurements for identifying otolith asymmetries possibly related to space motion sickness susceptibility

ActaAstronautica %1ol.33, pp. 1-8, 1994

Pergamon

0094-5765(94)00086-7

Copyright © 1994 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0094-5765/94 $7.00+0.00

TORSIONAL VESTIBULO-OCULAR REFLEX MEASUREMENTS FOR IDENTIFYING OTOLITH ASYMMETRIES POSSIBLY RELATED TO SPACE MOTION SICKNESS SUSCEPTIBILITY Robert J. Peterka, Ph.D. Good Samaritan Hospital & Medical Center Clinical Vestibular Laboratory 1040 N.W. 22 nd Ave., N010 Portland, OR 97210

ABSTRACT Recent studies by Diamond and Markham 1,2 have identified significant correlations between space motion sickness susceptibility and measures of d i s c o n j u g a t e t o r s i o n a l eye m o v e m e n t s r e c o r d e d during p a r a b o l i c flights. These results support an earlier proposal by von Baumgarten and Th~mler 3 which hypothesized that an asymmetry of otolith function between the two ears is the cause of space motion sickness. It may be p o s s i b l e to devise experiments that can be p e r f o r m e d in the 1 g environment on earth that could identify and quantify the presence of a s y m m e t r i c o t o l i t h function. This p a p e r s u m m a r i z e s the k n o w n physiological and anatomical properties of the otolith organs and the properties of the torsional vestibulo-ocular reflex which are relevant to the design of a stimulus to identify otolith asymmetries. A specific stimulus which takes advantage of these properties is proposed. INTRODUCTION Attempts to predict motion sickness susceptibility, and in particular space motion sickness susceptibility, have been generally unsuccessful. Many factors which play a role in motion sickness have been identified. These factors include receptor system physiology, neural coding of sensory information about body orientation in space, oculomotor and postural control reflexes, the perception of motion and orientation, and the interaction between motor behavior and perception. However, the correlations of these factors with motion sickness susceptibility are weaker than desired, and there has been poor transference of predictions of susceptibility from one setting to another. Recent studies by Diamond and Markham 1,2 have identified a strong correlation between prior history of space motion sickness s u s c e p t i b i l i t y in a s t r o n a u t s and their eye m o v e m e n t a s y m m e t r i e s identified during parabolic flights. Specifically, Diamond and Markham measured torsional eye position (ocular counterrolling) in both eyes at rest in a 1 g environment, and in the 0 g and 1.8 g periods during parabolic flight trajectories. With the 1 g measurements serving as a reference, they identified the existence of small disconjugate torsional eye positions in 0 g and 1.8 g conditions. The greater the difference between the disconjugate eye positions in the 0 g and 1.8 g conditions, the greater the likelihood that the astronaut had experienced motion sickness symptoms while on shuttle flights. Among those who had

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e x p e r i e n c e d m o t i o n sickness, the s e v e r i t y was c o r r e l a t e d w i t h the m a g n i t u d e of the d i f f e r e n c e b e t w e e n 0 g and 1.8 g d i s c o n j u g a t e eye torsion. An a s y m m e t r y of o t o l i t h f u n c t i o n b e t w e e n the two ears may be the cause of the torsional asymmetry. However, Diamond and M a r k h a m were not able to identify an ocular torsion asymmetry in any subject during roll tilts made in a 1 g environment, including subjects who had identifiable a s y m m e t r i e s in the 0 g and 1.8 g conditions. A reasonable explanation for this is that in the t e r r e s t r i a l e n v i r o n m e n t , otolith function a s y m m e t r i e s are well c o m p e n s a t e d by central nervous s y s t e m m e c h a n i s m s which e f f e c t i v e l y mask the e x i s t e n c e of the asymmetry. D i a m o n d and M a r k h a m ' s results support a t h e o r y put f o r w a r d by von B a u m g a r t e n and T h ~ m l e r 3. This t h e o r y p o s t u l a t e s that an a s y m m e t r y of otolith function between the two ears exists in some subjects and causes the neural a c t i v i t y a r i s i n g from the o t o l i t h organs in one ear to be unequal to a c t i v i t y of the other ear. In order to c o m p e n s a t e for this imbalance and p r o v i d e for normal v e s t i b u l a r f u n c t i o n under t e r r e s t r i a l conditions, the central nervous system generates a central neural tone that c o r r e c t s for the a s y m m e t r y . W h e n the s u b j e c t e n t e r s a 0 g e n v i r o n m e n t , the u n w e i g h t i n g of the o t o l i t h organs in the two ears p r o d u c e s a shift in the p e r i p h e r a l neural tone to new levels. The continued presence of the c e n t r a l c o m p e n s a t o r y t o n e in the 0 g e n v i r o n m e n t r e s u l t s in an e f f e c t i v e i m b a l a n c e of o t o l i t h function, p o s s i b l y l e a d i n g to the d e v e l o p m e n t of m o t i o n sickness symptoms. The theory of yon B a u m g a r t e n and ThOmler is a d d i t i o n a l l y s u p p o r t e d by the r e s u l t s of L a c k n e r et al. 4 L a c k n e r ' s r e s u l t s a c t u a l l y did show a correlation between asymmetric ocular torsion m e a s u r e d in 1 g and motion sickness susceptibility on parabolic flights. The correlation, however, was not large e n o u g h to a l l o w a c c u r a t e p r e d i c t i o n of m o t i o n sickness susceptibility. M o r e s e n s i t i v e tests for a s y m m e t r i c a l o t o l i t h f u n c t i o n have been p r o p o s e d by W e t z i g et al. 5. W e t z i g m e a s u r e d tilt p e r c e p t i o n and ocular t o r s i o n d u r i n g constant v e l o c i t y v e r t i c a l - a x i s r o t a t i o n s in which the subject's o r i e n t a t i o n with respect to the rotation axis v a r i e d so as to deliver asymmetric centrifugal accelerations to the two ears. E x p e r i m e n t s on a limited number of subjects r e v e a l e d results consistent with the e x i s t e n c e of a s y m m e t r i c o t o l i t h r e s p o n s e s . In addition, d i s c o n j u g a t e t o r s i o n a l eye m o v e m e n t s were o b s e r v e d i n d i c a t i n g that the otolith organ in a given ear exerts a stronger influence on ipsilateral as c o m p a r e d to c o n t r a l a t e r a l eye movements. This o b s e r v a t i o n tends to support the recent results of D i a m o n d and Markham, and indicates that b i n o c u l a r m e a s u r e m e n t s of ocular torsion could improve the s e n s i t i v i t y of tests of asymmetric otolith function. A l t h o u g h Wetzig's experiments were well conceived, the m a g n i t u d e of the d i f f e r e n t i a l a c c e l e r a t i o n applied to the two ears was small, about 0.07 g, possibly decreasing the l i k e l i h o o d that otolith a s y m m e t r i e s could be r e l i a b l y measured. In this paper we describe an a l t e r n a t i v e test stimulus that has the p o t e n t i a l of m o r e r e l i a b l y i d e n t i f y i n g the e x i s t e n c e of a s y m m e t r i c o t o l i t h function. The d e s i g n p r i n c i p l e s for c r e a t i n g an a p p r o p r i a t e stimulus are described. Since our k n o w l e d g e of the CNS p r o c e s s i n g of o t o l i t h signals is not sufficient to p r e d i c t the success of any given stimulus, e x p e r i m e n t s will be n e c e s s a r y to e v a l u a t e the e f f i c a c y and e f f i c i e n c y of a l t e r n a t i v e approaches.

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1.5

F i g u r e i. A typical otolith afferent stimulus - response f u n c t i o n r e l a t i n g the o t o l i t h a f f e r e n t d i s c h a r g e rate to the component of linear acceleration acting along the afferent's most s e n s i t i v e axis of s t i m u l a t i o n (adopted from Fernandez and Goldberg6) •

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Force (g's) STIMULUS D E S I G N P R I N C I P L E S A r e a s o n a b l e set of p r i n c i p l e s for the d e s i g n of s t i m u l u s and measurement techniques capable of d e t e c t i n g the existence and quantifying the magnitude of asymmetric otolith function are as follows: i. 2.

3.

4.

The stimulus should be b a s e d on the known p h y s i o l o g y of the o t o l i t h receptors. The stimulus should provide a linear acceleration stimulus that is as large as p o s s i b l e and will produce a d i f f e r e n t i a l effect on the two o t o l i t h organs. The s t i m u l u s s h o u l d be novel in the sense that s u b j e c t s w o u l d not t y p i c a l l y be e x p o s e d to the stimulus in e v e r y d a y life. (This w o u l d limit the likelihood that CNS compensatory mechanisms have m a s k e d the effects of a s y m m e t r i c otolith function.) For p r a c t i c a l p u r p o s e s , the s t i m u l u s and m e a s u r e m e n t t e c h n i q u e s s h o u l d not be so e x o t i c as to r e q u i r e e q u i p m e n t not c u r r e n t l y available.

PHYSIOLOGICAL

PROPERTIES

Otolith Nonlinear

Force-resPonse Properties

Otolith afferent neural responses show significant nonlinear response p r o p e r t i e s 6. Figure 1 shows a typical s t i m u l u s - r e s p o n s e c h a r a c t e r i s t i c curve of an o t o l i t h a f f e r e n t nerve fiber for a linear a c c e l e r a t i o n a c t i n g a l o n g the most s e n s i t i v e axis, the p o l a r i z a t i o n vector, of the afferent. The s t i m u l u s - r e s p o n s e curves vary from a f f e r e n t to a f f e r e n t in t h e i r h o r i z o n t a l and v e r t i c a l shift and scale factors, but the g e n e r a l n o n l i n e a r shape is consistent. On average, the 0 g point is l o c a t e d on a very n o n l i n e a r p o r t i o n of the stimulus response curve. For the utricular otolith organs, which to a first a p p r o x i m a t i o n lie in a h o r i z o n t a l p l a n e when the h e a d is in an u p r i g h t p o s i t i o n , the g r a v i t y v e c t o r e x e r t s an i n e f f e c t i v e compressional f o r c e on the u t r i c u l a r hair cells, and most a f f e r e n t s will be b i a s e d near the 0 g p o i n t s on their stimulus response curves. When the h e a d is r o l l e d 90 ° so that one ear is d i r e c t e d downward, o t o l i t h a f f e r e n t fibers whose p o l a r i z a t i o n vectors are oriented toward the downward ear will be b i a s e d to the steeper +I g point on their s t i m u l u s - r e s p o n s e curves, and

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R

R

I

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F Figure 2. Otolith afferent neural responses (R versus t) predicted during subject-on-side low amplitude, high frequency sinusoidal oscillations about an earth-horizontal axis with the subject's head displaced from the rotation axis. Most utricular otolith afferents in the upper ear will be biased toward the -i g operating point on the stimulus-response curves (R versus F), and in the lower ear toward the +I g operating point.

afferents with oppositely directed polarization vectors will be biased to the flatter -I g point. With the head in this ear-down orientation, any linear acceleration applied along a vertical axis (collinear with gravity) w o u l d t h e r e f o r e produce very different responses in the afferents with oppositely oriented polarization vectors. Specifically, afferents biased toward +i g would have larger resting discharge rates and show larger modulations in neural activity (larger gains) than afferents biased toward -i g. Asymmetrical

Otolith Morphology

Fernandez a n d G o l d b e r g 7 identified asymmetries in the distribution of polarization vectors within the otolith organs of the squirrel monkey. Specifically for the utricles, about 75% of the a f f e r e n t s had polarization vectors that were generally oriented toward the lateral direction. This asymmetry means that when a subject is oriented with one ear directed downward, most utricular afferents in that downward ear are b i a s e d t o w a r d their +i g o p e r a t i n g points and most utricular afferents in the opposite ear toward their -I g operating points. If a linear acceleration collinear with gravity is applied, on average the utricular otolith responses arising from the downward ear should be quite different from those from the upward ear (Figure 2).

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R

R i

i

I

F

F

R I

i

i

i

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t

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Figure 3. Prediction of utricular otolith afferent responses in a subject with asymmetric otolith function represented by different slopes for the stimulus-response curves (R versus F) in the two ears. The stimulus-response curve for the subject's right ear has a lower slope than the left ear. The identical low amplitude, high frequency, sinusoidal eccentric axis oscillations with the subject oriented with right ear down (left side plots) versus left ear down (right side plots) result in very different patterns of utricular otolith activity (R versus t) in the two head orientations.

Asymmetric

otolith function

The t h e o r y of a s y m m e t r i c o t o l i t h f u n c t i o n p o s t u l a t e d by von Baumgarten and T h O m l e r 3 can be e x p r e s s e d in terms of the otolith stimulus-response characteristic curves. A reasonable interpretation is that, on average, the slopes of the stimulus-response curves differ between the two ears, possibly due to differences in the effective otoconial mass. If a subject were tested with a vertical oscillating linear acceleration, first with one ear oriented downward, then with the other ear oriented downward (Figure 3), the otolith responses generated in the two head positions would be quite different. One would expect these differences to be reflected in differences in VOR eye movements. 2m~s/mmnl_~D~ A linear acceleration stimulus can evoke horizontal, vertical, or t o r s i o n a l V O R eye m o v e m e n t s d e p e n d i n g upon the d i r e c t i o n of the acceleration 8. Early experiments which measured ocular counterrolling in response to static tilts with respect to gravity showed only low

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RightEye "

-

(R-L)*5 J,,

JL

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. , li

LeftEye 10°I L

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F i g u r e 4. B i n o c u l a r r e c o r d i n g s of t o r s i o n a l eye m o v e m e n t s in response to a s i n u s o i d a l roll tilt stimulus (0.2 Hz, ±20 °) about an e a r t h - h o r i z o n t a l axis with h e a d on axis. Torsional measurements were d e r i v e d from video recordings. Systematic d i f f e r e n c e s b e t w e e n right and left eye t o r s i o n were o b s e r v e d (center trace). Large spikes are eye blink artifacts.

a m p l i t u d e t o r s i o n a l r e s p o n s e s 9. This led to the c o n c l u s i o n that the t o r s i o n a l c o m p o n e n t of VOR was u n i m p o r t a n t r e l a t i v e to the h o r i z o n t a l and v e r t i c a l components. However more recent results have shown that the gain of the t o r s i o n a l VOR during roll rotations (vertical canal and otolith stimulation) is c o m p a r a b l e to that of the h o r i z o n t a l and vertical c o m p o n e n t s I0,II, p a r t i c u l a r l y at higher stimulus frequencies 12. Therefore alterations of otolith function associated with 0 g conditions could have a s i g n i f i c a n t influence on t o r s i o n a l VOR dynamics, p o s s i b l y c o n t r i b u t i n g to i n c r e a s e d s e n s o r y c o n f l i c t and l e a d i n g to m o t i o n sickness. The t o r s i o n a l V O R has some u n u s u a l p r o p e r t i e s that c o u l d make it p a r t i c u l a r l y u s e f u l as a m e a s u r e r e l a t e d to o t o l i t h function. In c o m p a r i s o n to h o r i z o n t a l and v e r t i c a l VOR, the t o r s i o n a l V O R is less i n f l u e n c e d by visual i n f o r m a t i o n and is less i n f l u e n c e d by c o n s c i o u s a t t e m p t s to m o d u l a t e the reflex a m p l i t u d e by i m a g i n i n g e a r t h - f i x e d or s u b j e c t - f i x e d t a r g e t s d u r i n g m o t i o n s in the dark 13. The d i r e c t i o n of gaze and the vergence angle of the eyes are known to influence the gain of the h o r i z o n t a l and vertical VOR 14, but not the gain of the t o r s i o n a l VOR. Finally, some l i n e a r a c c e l e r a t i o n s , such as t h o s e a l o n g an interaural axis, are known to evoke torsional eye movements that are not c o m p e n s a t o r y in the sense that they do not serve to s t a b i l i z e gaze in space 8. The fact that this n o n - c o m p e n s a t o r y VOR exists, suggests that it is an artifact of an unusual force environment, and as such is likely to have e s c a p e d the actions of CNS m e c h a n i s m s that might otherwise mask the e f f e c t s of a s y m m e t r i c o t o l i t h function. Therefore, the use of a

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stimulus that evokes t o r s i o n a l VOR eye m o v e m e n t s as an indirect indicator of otolith function is likely to be less i n f l u e n c e d by u n c o n t r o l l e d e x p e r i m e n t a l variables which c o n f o u n d h o r i z o n t a l and vertical VOR responses. A CANDIDATE

STIMULUS

With minor m o d i f i c a t i o n s to available equipment, we p r o p o s e to deliver a low amplitude, high frequency, roll rotational stimulus (±5 °, 2 Hz) to subjects positioned with head about 0.8 m off-axis and oriented in both the right and left ear down positions. This stimulus produces an oscillating tangential acceleration with a peak value of i.I g acting essentially collinear with gravity, and with only a small centripetal acceleration with peak amplitude of 0.I g. Unfortunately a rotational stimulus also stimulates the vertical semicircular canals. The vertical canal responses, however, should be identical in both the right and left ear down positions, so that any difference in VOR responses in the two positions should be attributable to asymmetric otolith function. One would expect this stimulus to evoke both torsional and horizontal VOR eye movements. The torsional component would be driven by both otolith and vertical canal stimulation and the horizontal component probably would be d r i v e n by the interaural tangential linear acceleration. From the work of Paige 15, it is reasonable to expect that the gain of the horizontal component would depend upon vergence angle, and therefore it will be important to record eye movements binocularly in order to account for this variable. In addition, binocular recordings will allow detection of disconjugate torsional eye movements which might be an additional indicator of the presence of asymmetric otolith function. We have recently begun binocular video recordings of eye movements with off-line computer analysis of horizontal, vertical, and torsional eye p o s i t i o n using image p r o c e s s i n g t e c h n i q u e s similar to those described by Clarke et al. 16 An example of binocular recordings of torsional eye movements evoked by a head-on-axis roll rotation about an earth-horizontal axis is shown in Figure 4. The torsional eye movements p r o d u c e d by this m i l d stimulus (0.2 Hz, ±20 ° ) showed some small disconjugacy such that at maximum excursions of torsion, which typically occurred at maximum tilt positions, the intorting eye moved farther than the extorting eye. Given the mild nature of this stimulus, it would be s u r p r i s i n g if the d i s c o n j u g a t e torsion was the result of otolith asymmetry. Rather, orbital mechanics of the eye may be a contributor to disconjugate torsional eye movements, and t h e r e f o r e c o u l d be a confounding factor in the search for measurements reflecting otolith asymmetries. CONCLUSION We will shortly begin experiments using the stimulus described above, and will additionally measure torsional responses to rotational stimuli designed to replicate the work of Wetzig et al. (1990). If the two experiments give c o r r e s p o n d i n g results, this will p r o v i d e strong evidence for the existence of asymmetric otolith function in a normal population, and will m o t i v a t e the application of these results to prospective studies of space sickness susceptibility in astronauts.

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ACKNOWLEDGMENT This research

was supported by NASA grant NAG 9-117.

BIBLIOGRAPHY i. Diamond SG and M a r k h a m CH (1991) Prediction of space motion sickness s u s c e p t i b i l i t y by d i s c o n j u g a t e eye torsion in p a r a b o l i c flight. Aviat Space Environ Med 62:201-205 2. M a r k h a m CH and D i a m o n d SG (1992) F u r t h e r e v i d e n c e to support disconjugate eye torsion as a predictor of space motion sickness. Aviat Space Environ Med 63 (2):118-121 3. von B a u m g a r t e n RJ and T h 0 m l e r R (1979) A m o d e l for v e s t i b u l a r function in altered gravitational states. Life Sci Space Res 17:161-170 4. Lackner JR, Graybiel A, Johnson WH and Money KE (1987) A s y m m e t r i c otolith function and increased susceptibility to motion sickness during e x p o s u r e to v a r i a t i o n s in g r a v i t o i n e r t i a l a c c e l e r a t i o n level. Aviat Space Environ Med 58:652-7 5. W e t z i g J, R e i s e r M, M a r t i n E, B r e g e n z e r N and von B a u m g a r t e n RJ (1990) U n i l a t e r a l c e n t r i f u g a t i o n of the o t o l i t h s as a new m e t h o d to determine b i l a t e r a l asymmetries of the otolith apparatus in man. Acta A s t r o n a u t i c a 21:519-525 6. Fernandez C and Goldberg JM (1976) Physiology of peripheral neurons i n n e r v a t i n g o t o l i t h organs of the s q u i r r e l monkey. II. D i r e c t i o n selectivity and force-response relations. J N e u r o p h y s i o l 39:985-995 7. Fernandez C and Goldberg JM (1976) Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. I. Reponse to static tilts and to long-duration centrifugal force. J N e u r o p h y s i o l 39:970-984 8. Paige GD and Tomko DL (1991) Eye movement responses to linear head motion in the squirrel monkey. I. Basic characteristics. J Neurophysiol 65:1170-1182 9. Miller II EF (1970) Evaluation of otolith organ function by means of ocular counter-rolling measurements. In: Stahle J (ed) V e s t i b u l a r function on earth and in space. Pergamon Press, New York, pp 97-107 i0. Ferman L, C o l l e w i j n H, Jansen TC and van den Berg AV (1987) Human gaze s t a b i l i t y in the horizontal, v e r t i c a l and t o r s i o n a l d i r e c t i o n during v o l u n t a r y h e a d movements, e v a l u a t e d with a three d i m e n s i o n a l scleral induction coil technique. Vision Res 27:811-828 ii. Vi~ville T and Masse D (1987) Ocular c o u n t e r - r o l l i n g during active head tilting in humans. Acta Otolaryngol (Stockh) 103:280-290 12. P e t e r k a RJ (1992) Response c h a r a c t e r i s t i c s of the human torsional v e s t i b u l o - o c u l a r reflex. Ann NY Acad Sci 656:877-879 13. L e i g h RJ, M a a s EF, G r o s s m a n GE and R o b i n s o n DA (1989) V i s u a l c a n c e l l a t i o n of the t o r s i o n a l v e s t i b u l o - o c u l a r reflex in humans. Exp Brain Res 75:221-226 14. Paige GD and Tomko DL (1991) Eye movement responses to linear head m o t i o n in the squirrel monkey. II. V i s u a l - v e s t i b u l a r i n t e r a c t i o n s and kinematic considerations. J Neurophysiol 65:1183-1196 15. Paige GD (1991) Linear vestibulo-ocular reflex (LVOR) and modulation by vergence. Acta Otolaryngol [Suppl] (Stockh) 481:282-286 16. Clarke AH, Teiwes W and Scherer H (1991) V i d e o - o c u l o g r a p h y - an alternative m e t h o d for m e a s u r e m e n t of t h r e e - d i m e n s i o n a l eye movements. In: S c h m i d R, Z a m b a r b i e r i D (eds) O c u l o m o t o r C o n t r o l and C o g n i t i v e Processes. Elsevier Science Publishers B.V., North-Holland, pp 431-443