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Ocular torsion as a test of the asymmetry hypothesis of space motion sickness
Acta Astronautica Voi.27. pp. 11 - 17. 1992 Printed in Great Britain
0094-5765/92 $5.00+0.00 Pergamon Press Ltd
OCULAR TORSION AS A TEST OF THE ASYMMETRY HYPOTHESIS OF SPACE MOTION SICKNESS Shirley G. Diamond and Charles H. Markham UCLA School of Medicine, Department of Neurology Los Angeles, CA 90024-1769 USA
ABSTRACT Disconjugate eye torsion induced by O G and 1.8 G during parabolic flight was studied in nine former astronauts in 1990 and eight in 1991, four of whom were included in the previous experiment. The astronauts could be divided into two statistically significant groups on the basis of low and high scores of disconjugacy. When their histories of space motion sickness (SMS) were later revealed, all of the low scorers had not been sick on previous space flights; all the high scorers had had SMS. These data give support to the hypothesis that SMS in one-half or two-thirds of astronauts is due to an otolith, probably utricular, asymmetry in those persons. Ocular disconjugacy tended to increase at O G with increasing numbers of parabolas, this being particularly evident in those subjects with prior SMS. One conclusion: 10 to 20 parabolas are necessary to adequately discriminate those who are subject to SMS from those who are not. Tilting the subjects with high disconjugacy values and presumed otolith asymmetry by small amounts in right ear down or left ear down positions for several exposures to hypergravity did not reveal a lessened amount of ocular disconjugacy; there were actually increased amounts of ocular disconjugacy induced in the tipped positions. We suspect the increased disconjugacy caused by multiple parabolas may have masked any "null" point induced at 1.8 G by small head angulations. Space motion sickness (SMS) appears to be a unique form of motion sickness. It occurs within minutes to hours after entering microgravity environment, typically lasts the first 1 to 4 days in space flight, and may occur in abbreviated form on returning to earth. The symptoms are much like other forms of motion sickness except vomiting may occur with little warning. The substrate of SMS appears to be a loss of the constant force of gravity acting on the vestibular otolith system. In certain subjects in this "sensory mismatched" state, motion sickness may be easily triggered by linear and angular acceleration to the head and by visual stimuli. Between one-half and two-thirds of astronauts and cosmonauts have SMS 3 m and the remainder do not. The most likely explanation is the hypothesis advanced by von Baumgarten and Th0mler, 1 i.e. in certain individuals there is an asymmetry in the otolith apparatus on the two sides of the head which becomes compensated in a lifetime in a 1 G environment, but this compensation is lost when exposed to the hypogravlty of space flight. One thing that makes SMS unique is that there is no correlation with motion sickness in a earth-based environment, whether it be on land, sea or in the air. This is perhaps the main reason it has not been possible, until the present investigations, to predict who would get SMS. We shall review here work relating alterations in ocular torsional movements induced by repeated exposure to transient episodes of O G and 1.8 G during parabolic airplane flight to SMS. Several questions were asked: Could we predict in a blinded analysis which astronautsubjects had had prior SMS (and which had not)? Based on what appears to be a positive answer,4 we then asked whether the observed ocular torsional disconjugacy could be modified by an increasing number of parabolas; and whether observed disconjugacy seen in the subject in the upright position could be reduced or "nulled" by parabolic stimuli with the subjects tipped at different angles in the right ear down and left ear down directions.
M 27-c
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9th IAAManin SpaceSymposium
METHODS
AND
SUBJECTS:
Slowly rotating human subjects about their naso-occipital axes induces eye rotation opposite to the head rotation. The ocular torsion or ocular counterrolling (OCR), when done at constant velocity, does not stimulate the semicircular canals and is under reflex otolith control. The utricles appear to be the main or only responsible otolith organ.2,13,17 Based on earlier work of Kellogg, 10 we have developed a system of inducing ocular rotation during constant naso-occipital rotation, photographing both eyes simultaneously and determining the amount of OCR by visual superimposition of iral images. It is accurate to 0.1 ° eye torsion. Comparison of OCR in the two eyes has proven helpful in human disease states, including acoustic neuromas with and without brainstem compression, 5 benign paroxysmal positional vertigo 12 and spasmodic torticollis. 6 The same apparatus used in the patient population was bolted to the floor of the KC-135, over the wings and facing aft, and the subject's body held firmly by straps and side supports. The subject's head was held firmly by means of a bite bar. A single lens reflex camera was fixed about 13 cm in front of the subject's face. Two to 5 photographs were taken at O G and at 1.8 G, the photographs being taken only when a G meter indicated the above values. Data from each subject was taken during 10-20 parabolas. Nine astronauts were studied in the upright position. In a subsequent experiment, eight astronauts, including four astronauts from the previous study, were tested in four parabolas in the upright position, four parabolas when tipped 5 ° right ear down, four at 10° right ear down, four at 5 ° left ear down and four at 10 ° left ear down. The subjects were all former or present astronauts. All had had one to three previous space flights. Each recorded their prior SMS history on a form which they then sealed in an envelope. The envelopes were not opened until data analysis was completed some weeks later. The astronauts' observations were then converted into a well-recognized SMS evaluation scale. 3 When the flights, which were conducted at NASA Johnson Space Center, were completed, the data was analyzed at UCLA (see below). Ocular torsional asymmetry determinations were performed as indicated in Figure 1. Briefly, for one astronaut, the mean amplitude of ocular torsion at 1.8 G in the right eye in parabola 1 was
TORSIONAL
ASYMMETRY
( mean right eye amplitude minus mean left eye amplitude ) AstronautA -7, Parabola 1
right eve amplitude
1.8 G
left eve amplitude
-•
1"5° 2.5 ° 2.6°
.~
mean 2.2°
1'4~' 1.9° 1,5°
mean 1.6
°
right minus left 2.2 ° - 1.6° = .6°
.,~ 1'5° 0G 1'5° 1,6° mean 1.6°
1.21 /
1.o 8
~ " 0"7° " ~ 0'6° O5° mean 0.6°
.6 .4
slope =
~ 1~8G
right minus left 1.6° - 0.6 ° = 1.0° FIGURE 1. Computationof ocular torsional asymmetry. See text for details.
l 0G
.4
9th IAA Man in Space Symposium
13
determined from three (in this case) individual measures. Similar measures were made in the left eye. The mean left eye amplitude was subtracted from the right. The same steps were performed on data obtained at 0 G, parabola 1. The points were then plotted, the 1.8 G data to the left and the 0 G data to the right, and the slope determined. The same steps were performed for each subsequent parabola. Then a mean slope was calculated for that subject as a summary score of torsional asymmetry. The same steps were carried out on the data for all the subjects.
RESULTS: We found in our initial study in 19904 that four astronauts had low mean slopes of torsional asymmetry, and five had high values. The scores of the two groups differed significantly (p = 0.01, Wilcoxon rank sums test) 8 (see Figure 2). The envelopes containing the SMS history of the astronauts were then opened. The five with the high scores all had had SMS; none of the low scorers had SMS. Further, the magnitude of torsional asymmetry in the high scoring group was related to the severity of their SMS.
! TORSIONAL ASYMMETRY IN GROUND-BASED 1G
m m
_
_
m m m _
8.00
ILl O
_
_ram_
_
_mmm
-m~.
_
_
m
_
_
m m
_
_
m
-
-
,ram-
-
-
J
TORSIONAL ASYMMETRY IN HYPO- AND HYPERGRAVITY
2.00
Z < LU =E
mean = 0.08 (0.07)
.4--. p = 0.01--.~
mean = 1.17 (1.18)
1.00
_ I
A-9
. I
A-1
.
_ I
A-3
.... I
A-7
I
A-8
I
A-5
I
A-4
I
A-2
A-6
FIGURE 2. The top portion shows the 1 G disconjugate eye torsion scores. There were no differences between the subjects, all having low asymmetry. The lower portion depicts the infUght scores. The four astronauts with the lowest scores of torsional asymmetry in the hypo- and hypergravity on the KC-135 (shown with black bars) did not get sick in space. The five astronauts with the highest scores (gray bars) are those who had SMS on their space missions. Torsional asymmetry scores on the KC-135 differed significantly (p = 0.01) in the two groups. Severity of SMS was correlated with torsional asymmetry scores.
In 1991 we examined, in a blinded fashion, four new astronaut-subjects in a protocol of 20 parabolas - - four in upright position and four each at 5° and 10° right ear down and 5° and 10° left ear down. These four astronauts fell into two groups of two each, based on the magnitude of ocular disconjugacy, obtained from the data from the 20 parabolas. The difference in mean scores of the high and low scoring groups was significant at p = .015, (t-test) which is of special interest since the
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9th IAA Man in Space Symposium
number of subjects was so small (see Figure 3). When we opened the envelopes containing their SMS histories, we found the two with the highest ocular disconjugacy scores had had SMS, and the two with the lower scores had not. This is consistent with the earlier results in the nine subjects discussed above.
T O R S I O N A L A S Y M M E T R Y IN G R O U N D - B A S E D 1G FIVE POSITIONS
0.5
3.00-
T O R S I O N A L A S Y M M E T R Y IN HYPO- A N D H Y P E R G R A V I T Y FIVE POSITIONS
u,I n_
o
2.00 -
z
=E mean = 0.30 ( 0.05 )
q
p = 0.015
I~
mean = 0.85 (0.15)
1,oo-
I
I
I
I
A-10
A-11
A-12
A-13
FIGURE 3. Torsionaldisconjugacy in four former astronauts, tested in 1991, arranged in order of increasing scores. The low scorers, shown in black, did not have SMS; the high scorers had SMS. At the top of the figure are shown disoonjugacyvalues in 1 G; the scores are low and similarto each other.
We hypothesized that the two utricles in SMS subjects might be asymmetrical in shape, angulation or specific gravity, such that tipping the subject's head during 1.8 G stimuli might reduce or "null" the magnitude of torsional asymmetry (see Methods above). In this 1991 experiment, we used data from all eight astronaut subjects, four being new and four being subjects who had high torsional disconjugacy in the prior study. We found no significant lessening or reduction of ocular torsional asymmetry when the subjects were tipped 5° and 10 ° right ear down and 5° and 10 ° left ear down, being stimulated with four parabolas at each tipped head position. On the contrary, we found there was a tendency for increased ocular disconjugacy in the tipped positions. We then looked into the question of whether there were changes in torsional asymmetry with repeated parabolas, and whether it might be possible to use a lesser number than 10 or 20 parabolas to predict whether or not an individual might get SMS. For this analysis, we used 13 astronauts, 9 from the 1990 study plus the 4 new astronauts from the 1991 study. The latter we felt could be combined with the former, in spite of minor differences in protocols, since the results did not differ (see Figure 4). Looking at the data obtained from progressive sets of four parabolas, one can see a significant increase in torsional disconjugacy at O G with increasing numbers of parabolas (.001 ~ p <_.02, repeated measures ANOVA) in both those who had SMS and those who did not, but especially noteworthy in the SMS group. In 1.8 G torsional disconjugacy was far less than in O G and appeared to improve midway through the flight.
9th IAA Man in Space Symposium
15
TORSIONAL DISCONJUGACY IN 0 G AND 1.8 G
8M8 1.11G " NOSblS0G"
......... "
"
"
'
NO SMS 1.8 G ,0
1,40,0 ~P
,J >-
# #
1,20--
,f ~P
Z 0
#
1,10-,.J <
# # t # ~t
O ffl w Ill IT'
,80--
#
a Z
~
•
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.60-
O o o o o e
.50-
o o
o o o o
.40-
i
.10--
I
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1-4
5-8
9-12
13-16
17-20
PARABOLAS
FIGURE 4. Torsional disconjugacy, plotted against increasing number of parabolas, for all 13 subjects, increased in O G (gray and black dashed lines) (.001 ~; p < .02), especiallyin those with pdor historyof SMS (gray dashed line). DISCUSSION: Perhaps the most important finding of these investigations is that those astronaut-subjects whose ocular torsional disconjugacy is enhanced in KC-135 parabolic flight have a history of prior SMS. This was true in the original analysis of nine astronauts as well as in an additional four astronauts. While the numbers are still small, it appears likely this is the first predictive test of SMS. However, it should be recognized that this is a biological test and with further numbers of subjects, it is quite likely there will be false negatives and false positives. Nonetheless, these initial findings encourage us to encourage NASA to perform these ocular torsional analyses on all prospective astronauts. We emphasize this is for the purpose of using prophylactic medication and other measures in those persons who are likely to be affected by SMS.
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9th IAA Man in Space Symposium
Ocular counterrolling (OCR) is a type of ocular torsion induced by rotation of the subject's head, usually about the naso-occipital axis, in a gravitational field. Ocular torsion can also be induced by electrically stimulating the utricle.2,13,17 Its utricular origin is also supported by OCR demonstrating the same abnormalities when only the superior branch of the vestibular nerve is cut as when the entire vestibular nerve is severed. 11 Further, OCR has its greatest sensitivity when the subject's head (and the utricles) is close to upright. It is in these positions of slight tilt that shear, exerted by the otoconia on the underlying hair cells, is maximal. When a normal subject's head is upright, there is spontaneous ocular torsion ranging, peak to valley, up to 1.5°. 7 Is this ocular torsion also under utricular control? It seems so, since the magnitude of these spontaneous torsional movements is progressively enhanced when the head is tipped and maintained at 30 °, 60 ° and 90°. For all these reasons, we are inclined to ascribe changes in ocular torsion seen in our astronautsubjects at O G and 1.8 G to alterations in utricular reflex control rather than saccular influences. 14 We hoped by tipping the the astronauts to small angles to each side for four parabolas each that we might show a null point or minima in ocular disconjugacy induced at 1.8 G. This would have been consistent, for example, with Ross' demonstrating a major difference in otoconial mass between the paired otoliths in rats.15,16 However, we found no such reduction in ocular disconjugacy. On the contrary, there was an increase in disconjugacy in the tipped positions. If there were, in fact, changes suggesting a minima, they were masked by greater magnitude of ocular torsion seen in tipped head positions 7 and by progressively enhanced magnitude of ocular disconjugacy seen with repeated parabolas. It seems that the physiological demonstration of a structural asymmetry between the two utricles will have to be tested by recording from first order otolith afferents. As seen in Figure 4, there is clear increased magnitude of ocular disconjugacy in O G with repeated parabolas. One lesson from this: a predictive test for SMS will need no fewer than 10 to 20 parabolas on the KC-135. ACKNOWLEDGEMENTS:
We wish to thank Trent Wells for financially supporting this study; Noel Wheeler, Ph.D. for statistical consultation; and Setsuko Kashitani, Dan Stoller and Lynn Kashitani for technical support. We also wish to thank Bob Williams and other NASA KC-135 flight personnel, and especially all our astronaut-su bjects. REFERENCES:
1.
von Baumgarten RJ, Th~mler RA. A model for vestibular function in altered gravitational states. Life Sci. Space Res. 1978; 17:161-70.
2.
Blanks RHI, Anderson JH, Precht W. Response characteristics of semicircular canal and otolith systems in cat. II. Responses of trochlear motoneurons. Exp. Brain Res. 1978; 32-509-28.
3.
Davis JR, Vanderploeg JM, Santy PA, Jennings RT, Stewart DF. Space motion sickness during 24 flights of the space shuttle. Aviat. Space Environ. Med. 1988; 59:1185-9.
4.
Diamond SG, Markham CH. Prediction of space motion sickness susceptibility by disconjugate eye torsion in parabolic flight. Aviat. Space Environ. Med. 1991; 62:201-5.
5.
Diamond SG, Markham CH. Ocular counterrolling as an indicator of vestibular otolith function. Neurology 1983; 33:1460-9.
6.
Diamond SG, Markham CH, Baloh RW. Ocular counterrolling abnormalities in spasmodic torticollis. Arch. Neurol. 1988; 45:164-69.
7.
Diamond SG, Markham CH, Furuya N. Binocular counterrolling during sustained body tilt in normal humans and in a patient with unilateral vestibular nerve section. Annl Otol. Rhino, Laryngol. 1982; 91:225-9.
8.
Hollander M, Wolfe DA. Non parametric statistical methods. New York: John Wiley & Sons, 1973.
9.
Igarashi M. New facets of space medicine. Acta Otolaryngol. 1988; Suppl. 458:103-7.
9th IAA Man in Space Symposium
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10. Kellogg RS. Dynamic counterrolling of the eye in normal subjects and in persons with bilateral labyrinthine defects. The Role of the Vestibular Organs in the Exploration of Space. NASA SP77, 195, 1965. 11. Markham CH, Diamond SG. Do the eyes counterroll during barbecue rotation? Soc. Neurosci. Abstracts Vol. 9, Nov. 1983. 12. Markham CH, Diamond SG, Ito J. Utricular dysfunction in benign paroxysmal positional vertigo. In: The Vestibular Svstem: Neuroohvsioloaic and Clinical Research. Graham MD and Kemink JL (Eds). Raven Press, New York,-pp. 255-262, 1987. 13. Markham CH, Estes MS, Blanks RHI. Vestibular influences on ocular accommodation in cats. Equilibrium Res. 1973; 3:102-15. 14. Mittelstaedt H, Glasauer S. Determinants of spatial orientation in weightlessness.
Proc. of the Fourth European Symposium on Life Sciences Research in Space, Trieste, Italy, held from May 28-June 1, 1990, ESA SP-307, Nov. 1990.
15. Ross MD. Implications of otoconial changes in microgravity. Physiologist 1987; 30 (1) Suppl.: $90-3. 16.
Ross MD, Donovan KM. Otoconia as test masses in biological accelerometers: what can we learn about their formation from evolutionary studies and from work in microgravity? Scanning Electron Microscopy 1986; IV:1695-704.
17. Suzuki J-I, Tokumasu K, Goto K. Eye movements from single utricular nerve stimulation in the cat. Acta Otolaryngol. 1969; 68:350-62.
0094-5765/92 $5.00+0.00 Pergamon Press Ltd
OCULAR TORSION AS A TEST OF THE ASYMMETRY HYPOTHESIS OF SPACE MOTION SICKNESS Shirley G. Diamond and Charles H. Markham UCLA School of Medicine, Department of Neurology Los Angeles, CA 90024-1769 USA
ABSTRACT Disconjugate eye torsion induced by O G and 1.8 G during parabolic flight was studied in nine former astronauts in 1990 and eight in 1991, four of whom were included in the previous experiment. The astronauts could be divided into two statistically significant groups on the basis of low and high scores of disconjugacy. When their histories of space motion sickness (SMS) were later revealed, all of the low scorers had not been sick on previous space flights; all the high scorers had had SMS. These data give support to the hypothesis that SMS in one-half or two-thirds of astronauts is due to an otolith, probably utricular, asymmetry in those persons. Ocular disconjugacy tended to increase at O G with increasing numbers of parabolas, this being particularly evident in those subjects with prior SMS. One conclusion: 10 to 20 parabolas are necessary to adequately discriminate those who are subject to SMS from those who are not. Tilting the subjects with high disconjugacy values and presumed otolith asymmetry by small amounts in right ear down or left ear down positions for several exposures to hypergravity did not reveal a lessened amount of ocular disconjugacy; there were actually increased amounts of ocular disconjugacy induced in the tipped positions. We suspect the increased disconjugacy caused by multiple parabolas may have masked any "null" point induced at 1.8 G by small head angulations. Space motion sickness (SMS) appears to be a unique form of motion sickness. It occurs within minutes to hours after entering microgravity environment, typically lasts the first 1 to 4 days in space flight, and may occur in abbreviated form on returning to earth. The symptoms are much like other forms of motion sickness except vomiting may occur with little warning. The substrate of SMS appears to be a loss of the constant force of gravity acting on the vestibular otolith system. In certain subjects in this "sensory mismatched" state, motion sickness may be easily triggered by linear and angular acceleration to the head and by visual stimuli. Between one-half and two-thirds of astronauts and cosmonauts have SMS 3 m and the remainder do not. The most likely explanation is the hypothesis advanced by von Baumgarten and Th0mler, 1 i.e. in certain individuals there is an asymmetry in the otolith apparatus on the two sides of the head which becomes compensated in a lifetime in a 1 G environment, but this compensation is lost when exposed to the hypogravlty of space flight. One thing that makes SMS unique is that there is no correlation with motion sickness in a earth-based environment, whether it be on land, sea or in the air. This is perhaps the main reason it has not been possible, until the present investigations, to predict who would get SMS. We shall review here work relating alterations in ocular torsional movements induced by repeated exposure to transient episodes of O G and 1.8 G during parabolic airplane flight to SMS. Several questions were asked: Could we predict in a blinded analysis which astronautsubjects had had prior SMS (and which had not)? Based on what appears to be a positive answer,4 we then asked whether the observed ocular torsional disconjugacy could be modified by an increasing number of parabolas; and whether observed disconjugacy seen in the subject in the upright position could be reduced or "nulled" by parabolic stimuli with the subjects tipped at different angles in the right ear down and left ear down directions.
M 27-c
11
12
9th IAAManin SpaceSymposium
METHODS
AND
SUBJECTS:
Slowly rotating human subjects about their naso-occipital axes induces eye rotation opposite to the head rotation. The ocular torsion or ocular counterrolling (OCR), when done at constant velocity, does not stimulate the semicircular canals and is under reflex otolith control. The utricles appear to be the main or only responsible otolith organ.2,13,17 Based on earlier work of Kellogg, 10 we have developed a system of inducing ocular rotation during constant naso-occipital rotation, photographing both eyes simultaneously and determining the amount of OCR by visual superimposition of iral images. It is accurate to 0.1 ° eye torsion. Comparison of OCR in the two eyes has proven helpful in human disease states, including acoustic neuromas with and without brainstem compression, 5 benign paroxysmal positional vertigo 12 and spasmodic torticollis. 6 The same apparatus used in the patient population was bolted to the floor of the KC-135, over the wings and facing aft, and the subject's body held firmly by straps and side supports. The subject's head was held firmly by means of a bite bar. A single lens reflex camera was fixed about 13 cm in front of the subject's face. Two to 5 photographs were taken at O G and at 1.8 G, the photographs being taken only when a G meter indicated the above values. Data from each subject was taken during 10-20 parabolas. Nine astronauts were studied in the upright position. In a subsequent experiment, eight astronauts, including four astronauts from the previous study, were tested in four parabolas in the upright position, four parabolas when tipped 5 ° right ear down, four at 10° right ear down, four at 5 ° left ear down and four at 10 ° left ear down. The subjects were all former or present astronauts. All had had one to three previous space flights. Each recorded their prior SMS history on a form which they then sealed in an envelope. The envelopes were not opened until data analysis was completed some weeks later. The astronauts' observations were then converted into a well-recognized SMS evaluation scale. 3 When the flights, which were conducted at NASA Johnson Space Center, were completed, the data was analyzed at UCLA (see below). Ocular torsional asymmetry determinations were performed as indicated in Figure 1. Briefly, for one astronaut, the mean amplitude of ocular torsion at 1.8 G in the right eye in parabola 1 was
TORSIONAL
ASYMMETRY
( mean right eye amplitude minus mean left eye amplitude ) AstronautA -7, Parabola 1
right eve amplitude
1.8 G
left eve amplitude
-•
1"5° 2.5 ° 2.6°
.~
mean 2.2°
1'4~' 1.9° 1,5°
mean 1.6
°
right minus left 2.2 ° - 1.6° = .6°
.,~ 1'5° 0G 1'5° 1,6° mean 1.6°
1.21 /
1.o 8
~ " 0"7° " ~ 0'6° O5° mean 0.6°
.6 .4
slope =
~ 1~8G
right minus left 1.6° - 0.6 ° = 1.0° FIGURE 1. Computationof ocular torsional asymmetry. See text for details.
l 0G
.4
9th IAA Man in Space Symposium
13
determined from three (in this case) individual measures. Similar measures were made in the left eye. The mean left eye amplitude was subtracted from the right. The same steps were performed on data obtained at 0 G, parabola 1. The points were then plotted, the 1.8 G data to the left and the 0 G data to the right, and the slope determined. The same steps were performed for each subsequent parabola. Then a mean slope was calculated for that subject as a summary score of torsional asymmetry. The same steps were carried out on the data for all the subjects.
RESULTS: We found in our initial study in 19904 that four astronauts had low mean slopes of torsional asymmetry, and five had high values. The scores of the two groups differed significantly (p = 0.01, Wilcoxon rank sums test) 8 (see Figure 2). The envelopes containing the SMS history of the astronauts were then opened. The five with the high scores all had had SMS; none of the low scorers had SMS. Further, the magnitude of torsional asymmetry in the high scoring group was related to the severity of their SMS.
! TORSIONAL ASYMMETRY IN GROUND-BASED 1G
m m
_
_
m m m _
8.00
ILl O
_
_ram_
_
_mmm
-m~.
_
_
m
_
_
m m
_
_
m
-
-
,ram-
-
-
J
TORSIONAL ASYMMETRY IN HYPO- AND HYPERGRAVITY
2.00
Z < LU =E
mean = 0.08 (0.07)
.4--. p = 0.01--.~
mean = 1.17 (1.18)
1.00
_ I
A-9
. I
A-1
.
_ I
A-3
.... I
A-7
I
A-8
I
A-5
I
A-4
I
A-2
A-6
FIGURE 2. The top portion shows the 1 G disconjugate eye torsion scores. There were no differences between the subjects, all having low asymmetry. The lower portion depicts the infUght scores. The four astronauts with the lowest scores of torsional asymmetry in the hypo- and hypergravity on the KC-135 (shown with black bars) did not get sick in space. The five astronauts with the highest scores (gray bars) are those who had SMS on their space missions. Torsional asymmetry scores on the KC-135 differed significantly (p = 0.01) in the two groups. Severity of SMS was correlated with torsional asymmetry scores.
In 1991 we examined, in a blinded fashion, four new astronaut-subjects in a protocol of 20 parabolas - - four in upright position and four each at 5° and 10° right ear down and 5° and 10° left ear down. These four astronauts fell into two groups of two each, based on the magnitude of ocular disconjugacy, obtained from the data from the 20 parabolas. The difference in mean scores of the high and low scoring groups was significant at p = .015, (t-test) which is of special interest since the
t4
9th IAA Man in Space Symposium
number of subjects was so small (see Figure 3). When we opened the envelopes containing their SMS histories, we found the two with the highest ocular disconjugacy scores had had SMS, and the two with the lower scores had not. This is consistent with the earlier results in the nine subjects discussed above.
T O R S I O N A L A S Y M M E T R Y IN G R O U N D - B A S E D 1G FIVE POSITIONS
0.5
3.00-
T O R S I O N A L A S Y M M E T R Y IN HYPO- A N D H Y P E R G R A V I T Y FIVE POSITIONS
u,I n_
o
2.00 -
z
=E mean = 0.30 ( 0.05 )
q
p = 0.015
I~
mean = 0.85 (0.15)
1,oo-
I
I
I
I
A-10
A-11
A-12
A-13
FIGURE 3. Torsionaldisconjugacy in four former astronauts, tested in 1991, arranged in order of increasing scores. The low scorers, shown in black, did not have SMS; the high scorers had SMS. At the top of the figure are shown disoonjugacyvalues in 1 G; the scores are low and similarto each other.
We hypothesized that the two utricles in SMS subjects might be asymmetrical in shape, angulation or specific gravity, such that tipping the subject's head during 1.8 G stimuli might reduce or "null" the magnitude of torsional asymmetry (see Methods above). In this 1991 experiment, we used data from all eight astronaut subjects, four being new and four being subjects who had high torsional disconjugacy in the prior study. We found no significant lessening or reduction of ocular torsional asymmetry when the subjects were tipped 5° and 10 ° right ear down and 5° and 10 ° left ear down, being stimulated with four parabolas at each tipped head position. On the contrary, we found there was a tendency for increased ocular disconjugacy in the tipped positions. We then looked into the question of whether there were changes in torsional asymmetry with repeated parabolas, and whether it might be possible to use a lesser number than 10 or 20 parabolas to predict whether or not an individual might get SMS. For this analysis, we used 13 astronauts, 9 from the 1990 study plus the 4 new astronauts from the 1991 study. The latter we felt could be combined with the former, in spite of minor differences in protocols, since the results did not differ (see Figure 4). Looking at the data obtained from progressive sets of four parabolas, one can see a significant increase in torsional disconjugacy at O G with increasing numbers of parabolas (.001 ~ p <_.02, repeated measures ANOVA) in both those who had SMS and those who did not, but especially noteworthy in the SMS group. In 1.8 G torsional disconjugacy was far less than in O G and appeared to improve midway through the flight.
9th IAA Man in Space Symposium
15
TORSIONAL DISCONJUGACY IN 0 G AND 1.8 G
8M8 1.11G " NOSblS0G"
......... "
"
"
'
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FIGURE 4. Torsional disconjugacy, plotted against increasing number of parabolas, for all 13 subjects, increased in O G (gray and black dashed lines) (.001 ~; p < .02), especiallyin those with pdor historyof SMS (gray dashed line). DISCUSSION: Perhaps the most important finding of these investigations is that those astronaut-subjects whose ocular torsional disconjugacy is enhanced in KC-135 parabolic flight have a history of prior SMS. This was true in the original analysis of nine astronauts as well as in an additional four astronauts. While the numbers are still small, it appears likely this is the first predictive test of SMS. However, it should be recognized that this is a biological test and with further numbers of subjects, it is quite likely there will be false negatives and false positives. Nonetheless, these initial findings encourage us to encourage NASA to perform these ocular torsional analyses on all prospective astronauts. We emphasize this is for the purpose of using prophylactic medication and other measures in those persons who are likely to be affected by SMS.
16
9th IAA Man in Space Symposium
Ocular counterrolling (OCR) is a type of ocular torsion induced by rotation of the subject's head, usually about the naso-occipital axis, in a gravitational field. Ocular torsion can also be induced by electrically stimulating the utricle.2,13,17 Its utricular origin is also supported by OCR demonstrating the same abnormalities when only the superior branch of the vestibular nerve is cut as when the entire vestibular nerve is severed. 11 Further, OCR has its greatest sensitivity when the subject's head (and the utricles) is close to upright. It is in these positions of slight tilt that shear, exerted by the otoconia on the underlying hair cells, is maximal. When a normal subject's head is upright, there is spontaneous ocular torsion ranging, peak to valley, up to 1.5°. 7 Is this ocular torsion also under utricular control? It seems so, since the magnitude of these spontaneous torsional movements is progressively enhanced when the head is tipped and maintained at 30 °, 60 ° and 90°. For all these reasons, we are inclined to ascribe changes in ocular torsion seen in our astronautsubjects at O G and 1.8 G to alterations in utricular reflex control rather than saccular influences. 14 We hoped by tipping the the astronauts to small angles to each side for four parabolas each that we might show a null point or minima in ocular disconjugacy induced at 1.8 G. This would have been consistent, for example, with Ross' demonstrating a major difference in otoconial mass between the paired otoliths in rats.15,16 However, we found no such reduction in ocular disconjugacy. On the contrary, there was an increase in disconjugacy in the tipped positions. If there were, in fact, changes suggesting a minima, they were masked by greater magnitude of ocular torsion seen in tipped head positions 7 and by progressively enhanced magnitude of ocular disconjugacy seen with repeated parabolas. It seems that the physiological demonstration of a structural asymmetry between the two utricles will have to be tested by recording from first order otolith afferents. As seen in Figure 4, there is clear increased magnitude of ocular disconjugacy in O G with repeated parabolas. One lesson from this: a predictive test for SMS will need no fewer than 10 to 20 parabolas on the KC-135. ACKNOWLEDGEMENTS:
We wish to thank Trent Wells for financially supporting this study; Noel Wheeler, Ph.D. for statistical consultation; and Setsuko Kashitani, Dan Stoller and Lynn Kashitani for technical support. We also wish to thank Bob Williams and other NASA KC-135 flight personnel, and especially all our astronaut-su bjects. REFERENCES:
1.
von Baumgarten RJ, Th~mler RA. A model for vestibular function in altered gravitational states. Life Sci. Space Res. 1978; 17:161-70.
2.
Blanks RHI, Anderson JH, Precht W. Response characteristics of semicircular canal and otolith systems in cat. II. Responses of trochlear motoneurons. Exp. Brain Res. 1978; 32-509-28.
3.
Davis JR, Vanderploeg JM, Santy PA, Jennings RT, Stewart DF. Space motion sickness during 24 flights of the space shuttle. Aviat. Space Environ. Med. 1988; 59:1185-9.
4.
Diamond SG, Markham CH. Prediction of space motion sickness susceptibility by disconjugate eye torsion in parabolic flight. Aviat. Space Environ. Med. 1991; 62:201-5.
5.
Diamond SG, Markham CH. Ocular counterrolling as an indicator of vestibular otolith function. Neurology 1983; 33:1460-9.
6.
Diamond SG, Markham CH, Baloh RW. Ocular counterrolling abnormalities in spasmodic torticollis. Arch. Neurol. 1988; 45:164-69.
7.
Diamond SG, Markham CH, Furuya N. Binocular counterrolling during sustained body tilt in normal humans and in a patient with unilateral vestibular nerve section. Annl Otol. Rhino, Laryngol. 1982; 91:225-9.
8.
Hollander M, Wolfe DA. Non parametric statistical methods. New York: John Wiley & Sons, 1973.
9.
Igarashi M. New facets of space medicine. Acta Otolaryngol. 1988; Suppl. 458:103-7.
9th IAA Man in Space Symposium
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10. Kellogg RS. Dynamic counterrolling of the eye in normal subjects and in persons with bilateral labyrinthine defects. The Role of the Vestibular Organs in the Exploration of Space. NASA SP77, 195, 1965. 11. Markham CH, Diamond SG. Do the eyes counterroll during barbecue rotation? Soc. Neurosci. Abstracts Vol. 9, Nov. 1983. 12. Markham CH, Diamond SG, Ito J. Utricular dysfunction in benign paroxysmal positional vertigo. In: The Vestibular Svstem: Neuroohvsioloaic and Clinical Research. Graham MD and Kemink JL (Eds). Raven Press, New York,-pp. 255-262, 1987. 13. Markham CH, Estes MS, Blanks RHI. Vestibular influences on ocular accommodation in cats. Equilibrium Res. 1973; 3:102-15. 14. Mittelstaedt H, Glasauer S. Determinants of spatial orientation in weightlessness.
Proc. of the Fourth European Symposium on Life Sciences Research in Space, Trieste, Italy, held from May 28-June 1, 1990, ESA SP-307, Nov. 1990.
15. Ross MD. Implications of otoconial changes in microgravity. Physiologist 1987; 30 (1) Suppl.: $90-3. 16.
Ross MD, Donovan KM. Otoconia as test masses in biological accelerometers: what can we learn about their formation from evolutionary studies and from work in microgravity? Scanning Electron Microscopy 1986; IV:1695-704.
17. Suzuki J-I, Tokumasu K, Goto K. Eye movements from single utricular nerve stimulation in the cat. Acta Otolaryngol. 1969; 68:350-62.