Self-Motion Perception and Motion Sickness

168 Pages·8.9 MB·English

by  Fox, Robert A

I
m NASA-CR-194Z76
/d-,_ / ---_yZ._
=
ii_. i!__i_..!.i._.!
FIN_ORT
=for the Project
Self-Motion Perception and Motion Sickness.
NASA -Ames Cooperative_ Agreernent (NCC 2-167).
1982'1991
Principle Investigator: Robert A. Fox
-Department of Psychology
S_ Jose State University
_S_ Iose, CA 95192-0120
:_Tel: ........[phone]
:i
i1,1.................
(NASA-CR-194276) SELF-MOTION N94-21897 .,
PERCEPTION AND MOTION SICKNESS --THRU--
Final Report, 1982- 1991 (NASA) N94-21915
150 p Uncl as
i
G3/51 0185380
/
\
! .

f
TABLE OF CONTENTS
I. INTRODUCTION ............................................................................... 3
II. PRINCIPLE AREAS of INVESTIGATION ................................................. 3
A. Behavioral Measures ....................................................................... 3
1. Pica ....................................................................................... 4
2. CTA ...................................................................................... 4
3. Anorexia ................................................................................. 4
B. Effective Stimulus Parameters ............................................................ 5
C. Neuroanatomy and Physiology ........................................................... 5
1. Vasopressin ............................................................................. 5
2. Area Postrema .......................................................................... 6
3. Vagus Nerve ............................................................................ 6
4. Immunocytochemistry ................................................................. 6
D. Species Differences ........................................................................ 7
HI. CONCLUSIONS
IV. REFERENCES
V. LIST OF FIGURES
Figure 1. Mean Food Intake and Body Weight by Rats Exposed to Off-Vertical
Rotation .................................................................................... 10
Figure 2. Mean Food Intake and Body Weight by Rats Exposed to Parabolic
Flight ....................................................................................... 11
Figure 3. Mean Fluid Intake by Rats Prior to and Following Exposure to Parabolic
Flight ....................................................................................... 12
VI. APPENDIX I. RESEARCH PAPERS ................................................... 13
V. APPENDIX II. PAPERS PRESENTATED AT
SCIENTIFIC MEETINGS .............................................................. 15
2

41P
I. INTRODUCTION categories. These categories are used toorganize
the presentation of the results andtofacilitate the
Motion sickness typically is considered a discussion of motion sickness in animal models.
bothersome artifact of exposure to passive Thus, the results of these studies of motion
motion in vehicles of conveyance. This sickness inanimal models areorganized with the
condition seldom has significant impact on the following categories: (a) behavioral measures of
health of individuals because it is of brief the phenomenon, Co)stimuli that areeffective for
duration, it usually can be prevented by simply producing the phenomenon, (c) neuroanatomical
avoiding the eliciting condition and, when the structures and physiological events that are
conditions that produce it are unavoidable, related to the phenomenon, and (d) differences
sickness dissipates with continued exposure. between species in the elicitation of the
However, unavoidable motion sickness is a phenomenon.
malady that can have significant effects on the The rust two of these categories, behavioral
performance of affected individuals. Because the measures and effective stimuli, were addressed in
susceptibility of individuals to motion sickness the initial experiments because results from these
cannot be predicted with precision, some two categories of studies were fundamental to
individuals can be seriously affected if they are planning other experiments. After behavioral
required to work in anenvironment that produces measures had been subjected to initial validation
motion sickness. The affliction of individuals of and appropriate parameters were established for
unknown susceptibility by this malady can eliciting stimulation, studies were conducted to
become important when sickness could arise examine neural structures and physiological
during periods where complicated but necessary events that were related to motion sickness. As
performance is demanded. The occurrence of studies related to these questions progressed, the
space motion sickness during entry into or return issue of species differences inthe response began
from space flight is one possible case of this to arise and this was subjected to both
type. Important human activities are required retrospective analysis and direct experimental
during launch and landing of the Space Shuttle, examination.
precisely the times when "space sickness" can
occur. A. Behavloral Measures
There is some debate about the equivalence of
motion sickness produced in ground-based studies Frank sickness, or vomiting, is the only
and "space sickness". However, ground-based universally accepted response that defines motion
studies provide certain benefits over flight sickness in all species. None-the-less, many
studies. Ground-based studies can beconducted at other responses (e.g., pallor, increased salivation,
considerable cost savings, the necessary conlax)l defecation) are commonly considered tobe partof
conditions can be included with experimental the general syndrome of motion sickness. In
rigor, and the appropriate number of subjects an studies of motion sickness in humans nausea, a
be used to address the experimental questions. measure that is obtained only by self report,
Because there are numerous similarities between commonly is used as a prominent prodromal
motion sickness and space sickness, it appears symptom of sickness.
that better knowledge of motion sickness could Nausea and otherprodromalsymptoms that are
significantly benefit the understanding and future detected by self report canbe used inhumans, but
study of space sickness. there are no reliable methods for obtaining self
The studies conducted in this research project reports of symptoms in animals. Because of
examined several aspects of motion sickness in this, two alternative methods are used to assess
animal models. A principle objective of these the development of motion sickness in animal
studies was to investigate the nem'oanatomy that models. One system isto userating scales based
is important in motion sickness with the on the assessment of various responses that are
objectives of examining both the utility of putative _al symptoms. Such scales have
putative models and def'ming neural mechanisms been developed for use with cats, squirrel
that are important in motion sickness. monkeys and chimpanzees (Fox, 1992). An
extensive disenssion of rating scales with
animals is presented by Daunton (1989). The
II. PRINCIPLE AREAS of
second strategy is touse specific responses (e.g.,
INVESTIGATION
conditioned taste aversion) that are thought to be
related to neural or physiological mechanisms
For purposes of exposition, the studies and that underlay motion sickness. This swategy has
research findings have been classified into four been used with animals that do not have a
i
complete emetic reflex and as multiple or equally crucial for the production of motion
supplemental indices of sickness (Ossenkopp & sickness in man and CTA in animals. This, and
Ossenkopp, 1985). other relevant relations are reviewed in Fox
(1990).
Experimental studies were conducted to In this project itwas demonstrated that CTA is
evaluate pica, conditioned taste aversion (CTA), produced by exposure to several forms motion of
and anorexia as putative measures of motion moderate magnitude that are known to produce
sickness. Pica was proposed as a measure of vomiting in animals with a complete emetic
gastric distress and motion sickness by Mitchell reflex and in humans (Fox & Daunton, 1982;
(1977). This response was selected for Fox et a/., 1984). However, the precise utility
assessment because it results as increased of CTA as a measure of motion sickness remains
responding rather than as reduced responding to be described. A paramount concern in this
which is common with many of the other regard is that the relationship between vomiting
putative measures for animal models (Fox, and CTA is not isomorphic in either cats or
1990). CTA is the measure most commonly squirrel monkeys (Fox et al., 1990). Because
asserted andbest documented for assessing nausea CTA is not precisely related to the universal
and sickness in animals. Anorexia commonly symptom of motion sickness in species with a
occurs with motion sickness in humans and complete emetic reflex, the validity of CTA asa
anecdotally also inanimals that have a complete prodromal symptom in these species and as a
emetic reflex. Consequently this m_ure _as prima?Tindex of sickness in rodents that fail to
evaluated inseveral experiments. vomit isuncertain, i
1. Pica. 3. Anorexia,
Pica was studied in rats with sickness induced Two experimentswere conductedto directly
by vertical and off-vertical rotation at 1500/s. testanorexicandconditioningeffects ofmotion
No reliable pica response was produced by this These effects were assessed byexposing animals
treatment when appropriate groups were used to to either off-vertical rotation or to parabolic
control for confounded effects offood deprivation. flight using 15parabolas ina Lear jet. Anorexia
Pica could be induced byexposing food-deprived was assessed inrats permitted to feed for 2h per
animals to motion, but food deprivation itself day with exposure to motion on test days
also induced pica. occurring just prior to the feeding session. CTA
This result is in contrast to data reported by was conducted using procedures described
Mitchell (1977). It should be noted, however, elsewl_e (FtJt-&_Da--_tbn, i982).:
that studies showing pica in rats have used The mean clmqyconsumption of food in the
intense motion stimuli (e.gl, 7_500_//s)or severe experinient u_g-__ ro_ta_u'0nis shown
gastric irritants as inducing treatments. The in Figure 1. Food consumption increased and
purpose of these preliminary studies in this body weight decreased over the initial days of
project was to investigate whether pica could be adaptation to_sm'cted feedingregimen (2
produced in rats using moderate motion h/day) Until intak_-stab_ized by about Day ii.
conditions that were representative of treatments Using Day-i9 (the _y p_ding e_posure to
known to produce motion sickness in man and motion) as a baseline, anorexia was present on
other animals. In that regard the answer to the the day of exposure to motion (on Day 20,
experimental question was that pica was not a ps<.001) but intake on Days 21 & 22 did not
useful measure. differ from _a?seline 09>.39). Body weight _was
suppress-ed on_eacliOf the _ days foilowing
2. CTA. exposure to mofion-(ps<:00_L.?_?:_ =_ := ....
It _long _n reco_ed that CTA canbe The mean daily consumption of food in the
produced by numerous interventions, including experimeh/-u-sing-i_arabislic flight is shown in
motion, that are known to produce gastric Figure 2. Again, food consumptio_reas_as
distress in humans and animals. This the animals ada_C_to the-regth_c_d-V-eefdi-n-g
relationship between CTA and "internal malaise" schedule (2h/day) with body weight reflecting an
has led to widespread interest in using CTA to initial decrease fin'st 5-daysjT-0Ilbwed by a
assess several forms of sickness arising from normaltendencyto increaseO.n Da_ i2therats
gastric disruption in animal models. Several were_sportedto theflighltinean_ioadedon
theairp_netodeterminewhetherthisactivit,y
observations have indicated that CTA may be a
useful measure of motion sickness in animal wouldaffectthedependenmteasuresN.'oeffects
models. Important among these is the where se_n oh eFthe-F-f_ood-ih-_tOakr_lx_lyweight
demonstration that an intact vestibular system is with this procedure (F<I). With Day 18 as a
4
baseline, anorexia was present immediately after models was examined in several experiments.
the flight (Day 19) and 48 h late_r (Day 20). Two general resul_ were documented with these
Food consumption 72 h after the flight did not experiments: (a) motion sickness can be produced
differ from that preceding the flight (p>.80). in rodents, cats, and squirrel monkeys with
Food intake was suppressed immediately and 24 moderate stimulation that is comparable to that
h following flight (ps<.002) but by 48 h after which elicits sickness in humans; Co)stimuli
the flight food intake did not differ from the that are very provocative for one species may be
baseline (p>. 11). quite ineffective for producing sickness inanother
The effects if parabolic flight on CTA are species.
shown in Figure 3. Intake of flavored fluid by Conditioned aversion can be produced in
animals in the Control and Flight groups did not rodents with rotational stimulation that is of the
differ prior to the flight, but in the test following magnitude that produces vomiting in squirrel
parabolic animals inthe Control group consumed monkeys, chimpanzees, and humans (Fox &
more fluid than did the animals in the Flight Daunton (1982); Fox et al., 1984). Further, this
group (p<.001). It should be noted that the same stimulation can produce CTA in both cats
strength of conditioning is rather weak. There and squirrel monkeys (Fox et al., 1990). Thus,
was no significant suppression of intake in it is clear that conditioned aversions do not
animals exposed to flight. Rather, these animals depend onsevere motion challenges.
failed to increase intake as was seen in animals Detailed examination of eliciting stimuli in
from the Control group. Thus, a release from squirrel monkeys reflected that exposure to
neophobia in Control animals with a failure to stimuli of increasing intensity to humans also
observe this release in Fight animals appears to elicited more severe sickness in the monkey (Fox
create this difference. et al., 1982). An important result in this study,
The observed suppression of food intake could however, was the finding that stimuli that are
be a form of anorexia similar to that produced extremely provocative for humans are effective
during prolonged exposure of animals to hyper- for the squirrel monkey only when there is a
gravity during centrifugation, or to hypo-gravlty requirement for the animal to maintain posture.
during orbital flight. The coincident emergence When animals were exposed to provocative
of anorexia and CTA is consistent with the stimuli (cross-coupled stimulation) while
proposal that the rats became motion sick during movement was restricted at both the neck and
the altered gravity during the brief exposures to waist, the same stimulus that elicited sickness
parabolic flight. The magnitude of flight-induced with waist restraint only no longer was effective.
anorexia is as great as, or greater than that Thus, it appears that a requirement for postural
produced by a form of passive, cross-coupled control during passive motion is necessary if
stimulation that is very provocative for humans. motion sickness is to be elicited.
A)Anorexia following parabolic flight was Examination of the role of vision in motion
present for 48 h while that produced by rotation sickness produced the first demonstration of
was absent after only 24 h. vomiting in cats and squirrel monkeys by visual
Informal observations regarding anorexia were stimulation alone (Daunton et al., 1985).
conducted in both cats and squirrel monkeys-to - Sickness induced by visual stimulation alone is
begin examination of this effect in animals With known in man and is very disruptive in certain
a complete emetic reflex. Both cats and squirrel instances (e.g., "simulator sickness), but this has
monkeys were repeatedly observed toeatthefood not been shown previously in an animal model.
normally contained in their diets (cat food and With regard to the problem of prediction, it was
bananas respectively) within afew minutes (e.g_ .... shown in this research that animals more prone
less than 5 rain) after vomiting. These to sickness by passive, whole-body stimulation
observations indicate that anorexia is not _ also were more likely to become sick by
necessarily present when the universally accepted optokinetic stimulation alone.
indicator of motion sickness occurs. These
effects have not been satisfactorily resolved as
not formal experiments were conducted to test C. Neuroanatomy and Physiology
this issue further.
1. Vasopressln.
Vasopressin (AVP) is elevated in humans
B. Effective Stimulus Parameters duringreportsofnauseaandfollowingvomiting
(seeFox. 1992 for areview). PlasmaAVP is
The specific parameters of stimulation that dramaticallyelevatedincatsfollowingvomiting
effectively produce motion sickness in animal but the resting level of AVP in blood plasma
5
does not differ among cats that are selected tobe GABAergic terminals in the area postrema,
highly susceptible or very resistant to linear nucleus tractus solitarius, area sub-postrema, and
acceleration. On the other hand, AVP in gelatinous nucleus closely resembles that of
cerebrospinal fluid (CSF) is not elevated vagal afferent projections (D'Amelio et al.,
following motion sickness, but resting levels of 1988). In addition, the depletion of GAD
AVP in CSF are lower in animals that vomited immtmoreactive in these areas after electrical
during motion than in those animals which did stimulation of the vagus nerve seems toconfu'm
not vomit (Fox et al., 1987). The precise that at least part of the GABAergic activity
mechanism for the release of AVP during shown here corresponds with vagal afferents.
motions sickness could not be determined. The additional demonstration of substance P
Systemic injection of AVP at dosages calculated immunoreactivity in this study implies there
to produce levels equivalent to those observed may be important neuromodulatory functions
following vomiting failed to produce vomiting or mediated by neuropeptides.
to influence the onset of vomiting in cats that
were susceptible or resistant to to linear
acceleration (Unpublished Data). D. Species Differences
2. Area Postrema. While conducting the studies discussed above
Experiments using the lesion technique to to evaluate behavioral measures of and effective
examine the role of the area postrema showed stimuli for motion sickness it became
that: (a) The area postrema is not involved in increasingly obvious that stimuli that elicited
CTA that is produced by motion in rats (Sutton sickness and the syndromes observed indifferent
et at., 1988); (b) Neither CTA nor vomiting are species varied greatly. For example, linear
crucially dependent on the area postrema ineither acceleration, particularly earth-vertical
cats or squirrel monkeys (Fox, Corcoran & acceleration, is an especially effective stimulus
Brizzee, 1990). In combination with work by for eliciting motion sickness in cats while
Borison and Borison (1986), these findings vertical axis rotation isremarkably noneffective.
contributed to a reevaluation of the role of the On the other hand, vertical axis rotation is very
area postrema in vomiting induced by motion provocative for the squirrel monkey while linear
(Daunton et al., 1987). several authors have now acceleration has only minimal effectiveness with
proposed the,odes which include several additional thisspecies. -
brainstem and/or circumventricual smactures in Spec.ies differences can occur in rather closely
the emetic response (see Fox, 1992 for related species where similar reactions to stimuli
references). might be expected. For example, although
vertical axis rotation is very provocative for
3. Vagus Nerve. squirrel monkeys, we were unable tomake rhesus
A possible role for the vagus nerve in monkeys motion sick with this stimulus
responses to motion is implied by results (Corcoran, Fox, & Daunton, I990). In fact,
showing that the vagus nerve is crucial to CTA both anecdotal and experimental evidence indicate
induced in rodents by exposure to motion (Fox & that the rhesus monkey is highly resistant to
McKenna, 1988). Combined with other research, motion sickness. Workers in the Russian space
this finding shows that both vestibular and programhave reported "space sickness_but there
gastric neural systems contribute to the have been no well controlled studies reporting on
formation of CTA when motion is the stimulus. these effects (see Daunton, 1990 for a review of
The specific mechanism by which gastric these points).
circuitry functions is unknown (Fox, Sutton, & Difference of this type complicate the selection
McKenna, 1988), but we did provide evidence of appropriate animal models for studying the
indicating that gastric afferents of the rat remain emetic reflex in general and motion sickness or
active for an extended period following brief the space adaptation syndrome in particular.
physiological stimulation (Nijiima et al., 1987; Animal models will be crucial to the discovery
1988). and understanding of neurophysiological
mechanisms of these phenomena, but
4. Immunocytochemlstry. considerable research will be required before
Preliminary evidence indicating arole for the answers come forth.
vagus nerve either in motion sicknessor in
adaptationtostimuliproducingmotion sickness
hasbeen shown. Using immunocytochemistry
we showed that the distribution pattern of
6
motor coordination, postural reflexes, etc.).
III. CONCLUSIONS
Consequently, it is reasonable to expect that
many systems may be undergoing significant
All of the behavioral responses that have been changes (i.e., adaptations) during periods when
examined as measures of motion sickness in motion sickness occurs. In fact, one way to
animals are less than ideal. The only response avoid motion sickness isto select a behavior that
that is universally accepted as a valid measure is prevents adaptation of motor systems such as
vomiting. On initial consideration this appears lying down or going to sleep. In this regard it
tobe a serious weakness in this area of research. should be noted that motion sickness occurred in
However, it should be recognized that no other squirrel monkeys only when there was a
measures have been universally accepted for the necessity to maintain posture. This hypothesis
assessment of motion sickness in humans. The would suggest that motion sickness might
most commonly used additional measure in simply be an unfortunate outcome of normal
human studies is nausea, but the assessment of processes of adjusting the neuromuscular system
nausea, even inhumans can be quite inaccurate. to new, atypical environmental conditions.
Furthermore, there are no recognized Although the specific mechanisms that may be
physiological correlates of nausea in humans, involved in such processes are obscure at this
further complicating the assessment of this time, discovery of the physiology and neural
response in animals. changes that underlie adaptation may predict the
The issue of prediction of susceptibility to mechanisms that elicit motion sickness.
motion sickness also is difficult. Significant
attention has been directed to the problem of
prediction inhumanswithonlyminimalsuccess.
Whilewe foundsome evidenceforpredictive
valueinthelevelofAVP inCSF, thiseffect
wasnothighlypredictivaendsignificawnotrk
wouldbcrequiretdounderstantdhisrelationship
adequately.As isthecaseinhumans,plasma
AVP wasdramaticalellyevateidncatsfollowing
vomiting,but therewas no evidencein this
research to indicate that the level of system AVP
was predictive of susceptibility to motion
sickness.
It is now abundandy clear that previous
conceptions of the area postrema as a vomiting
center in motion sickness were premature and
incorrect. This conceptualization arose, in part,
from over-interpretation of lesion experiments
before many of the techniques of neuroscience
that are in common use today were available.
With present knowledge, many workers now
propose by that the emetic reflex ismediated via
circuitry in several circumventricular and
brainstem regions. Important work remains to
provide understanding of the specific neural
mechanisms of the response that is so important
indisease and travel by modem conveyances.
Ageneral hypothesis that was developed during
the course of this research project is that motion
sickness is a phenomenon that may reflect only
one of the outcomes of the more general effects
of adaptation to unusual environmental
conditions. Motion sickness arises when
organisms are subjected to passive motion that
results in atypical linear forces on the vestibular
system. Passive motion of this type can elicit
significant and pervasive adaptive responses in
many systems other than the emetic reflex (e.g.,
7
IV. REFERENCES Fox, R. A., & Daunton, N. G. (1982).
Conditioned feeding suppression in rats
Borison, H. L., & Borison, R. (1986). Motion produced by cross-coupled and simple motions.
sickness reflex arc bypasses the area posu'ema Aviation, Space and Environmental
in cats. Experimental Neurology, 92, Medicine, 53, 218-220.
723-737.
Fox, R. A., Daunton, N. G., & Coleman, J.
D'Amelio, F., Gibbs, M. A., Mehler, W. R., (1982). Susceptibility of the squirrel monkey
Daunton, N. G., & Fox, R. A. (1988). to several different motion conditions.
Immunocytochemical localization of glutamic Neuroscience Abstracts, 8, 698.
acid decarboxylase (GAD) and substance P in
neural areas mediating motlon-induced emesis. Fox, R. A., Corcoran, M., & Brizzee, K. R.
Effects of vagal stimulation on GAD (1990). Conditioned taste aversion and motion
immunoreacitivty. In J. C. Hwang, N. G. sickness in cats and squirrel monkeys.
Daunton, & V. Wilson fEds.). Basic and Canadian Journal Physiology and
applied aspects of vestibular Pharmacology, 68, 269-278.
function. Hong Kong: Hong Kong
University Press. Fox, R. A., Keil, L. C., Daunton, N. G.,
Crampton, G. H., & Lucot, I. (1987).
Daunton, N. O. (i990). Animal models in Vasopressin and motion sickness in cats.
motion sickness research. In G. H. Crampton Aviation, Space and Environmental
fed.) Motion and space sickness. Boca Medicine, 58 (Suppl. A), A143-A147.
Raton: CRC Press.
Fox, R. A., Lauber, A. H., Daunton, N. G.,
Daunton, N., Brizzee, K., Corcoran, M., Phillips, M., & Diaz, L. (1984). Off-vertical
Crampton, G., D'Amelio, F., Elfar, S., & rotation produces conditioned taste aversion and
Fox, R. (1987). Reassessment of area suppressed drinking in mice. Aviation,
postrema's role in motion sickness and Space and Environmental Medicine,
conditioned taste aversion. In J. C. Hwang, 55, 632-635.
N. G. Daunton, & V. Wilson feds.). Basic
and applied aspects of vestibular Fox, R. A., Sutton, R. L., & McKenna, S.
function. Hong Kong: Hong Kong (1988). The effects of area postrema lesions
University Press, p. 235. and selective vagotomy upon motion-induced
conditioned taste aversion. In J. C. Hwang, N.
Daunton, N. G., Fox, R. A., & Crampton, G. G. Daunton, & V. Wilson (Eds.). Basic and
H. (1985). Susceptibility of cat and squirrel applied aspects of vestibular
monkey tomotion sickness induced by visual function. Hong Kong: Hong Kong
stimulation: Correlation with susceptibility to University Press.
vestibular stimulation. In M e tio n
sickness: Mechanisms, prediction and Mitchell, D., Knlsemark, M. L., & I-Iafner, F.
treatment. (Proceedings of Advisor Group (1977). Pica: A species relevant behavioral
for Aerospace Research and Development). assay of motion sickness in the rat.
North Atlantic Treaty Organization, pp. 31-1 Physiology and Behavior, 24, 1095-
to 31.5. 1100.
Fox, R. A. (1990). Investigating motion Niijima, A., Jiang, Z-Y, Daunton, N. G., &
sickness using the conditioned taste aversion Fox, R. A. (1987). Effect of copper sulfate on
paradigm. In G. H. Crampton fed.). Motion the rate of afferent discharge in the gastric
and sickness sickness research. Boca branch of the vagus nerve in the rat.
Raton: CRC Press. Neuroscience Letters, 80, 71-74.
Fox, R. A. (1992). Current status: Animal Niijima, A., Jiang, Z-Y, Daunton, N. G., &
models of nausea. In A. L. Bianchi, L. Grelot, Fox, R. A. (1988). Experimental studies on
A. D. Miller, & G. L. King feds.). gastric dysfunction in motion sickness:The
Mechanisms and control of emesis. effectof gastric andvestibularstimulationon
London: JohnLibbey Eurotext Ltd. thevagalgastriceffcrents. In J.C.Hwang, N.
G. Dannton,& V. Wilson fEds.). Basicand
applied aspects of vestibular
8