NASA Technical Reports Server (NTRS) 19960020463: Self Motion Perception and Motion Sickness

18 Pages·4 MB·English

by  NASA Technical Reports Server (NTRS)

TABLE OF CONTENTS
. ...............................................................................
I INTRODUCTION 3
.................................................
I1. 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 Immunoc y toe hemis try 6
. ........................................................................
D Species Differences 7
.
111 CONCLUSIONS
. ................................................................................
IV REFERENCES 8
.
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 11 PAPERS PRESENTATED AT
..............................................................
SCIENTIFIC MEETINGS 15
2

1. INTRODUCTION categories. These categories are used to organize
the presentation of the results and to facilitate 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 in animal models are org with the
condition seldom has significant impact on the following categories: (a) behavid measures of
health of individuals because it is of brief the phenomenon, (b) stimuli that are effective €or
duration, it usually can be prevented by simply producing the phenomenon, (c) nernnanatomical
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 first two of these categories, behavioral
performance of af'fected individuals. Because the measures and effective stimuli, were addressed in
susceptibility of individuals to motion sickness the initial experiments because mulis 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 an environment 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 rem issue of species differences in the 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, examiaation.
precisely the times when "space sickness" can
occur. A. Behavioral 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, pund-based universally accepted response that defines motion
studies provide certain benefits over flight sickness in all species. None-the-less, many
studies. Gmd-based studies can be Conducted at other responses (e.g., pallor, increased salivation,
considerable cost savings, the necessary control defecation) are commonly considered to be part of
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 MUS^^, 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 other prodramal symptoms that are
significantly benefit the understanding and future deected by selfneport can be used m humans, 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 neuroanatomy that models. One system is to use rating 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 prodromal symptoms. Such scales have
putative models and defining neural mechanisms been developed for use with cats, squirrel
that are important in motion sickness. monkeys and chimpanzees (Fox, 1992). An
extensive discussion of rating scales with
animals is presented by Daunton (1989). The
II. PRINCIPLE AREAS of second strategy is to use specific responses (eg.,
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 strategy has
research findings have been classified into four been used with animals that do not have a
3
complete emetic reflex and as multiple or equally crucial for the production
supplemental indices of sickness (Ossenkopp & sickness in man and CTA in animals.
Ossenkopp, 1985).
Experimental studies were conducted to
evaluate pica, conditioned taste aversion (CTA),
and anorexia as putative measures of motion
sickness. Pica was proposed as a measure of
gastric distress and motion sickness by Mitchell
(1977). This response was selected for
assessment because it results as increased
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 er al., 1990). Because
asserted and best 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 as a
anecdotaIIy also in animals that have a complete prodromal symptom in these species and as a
emetic reflex. Consequently this measure was primary index of sickness in rodents that fail to
evaluated in several experiments. vomit is uncertain.
1. Pica. 3. Anorexia.
Pica was studied in rats with sickness induced Two experiments were conducted to directly
by vertical and off-vertical rotation at 150°/s. test anorexic and conditioning effects of motion.
No reliable pica response was produced by this These effects were assessed by exposing animals
treatment when appropriate groups were used to to either off-vertical rotation or to parabolic
control for confounded effects of food deprivation. flight using 15 parabolas in a Lear jet. Anorexia
Pica could be induced by exposing fooddeprived was assessed in rats permitted to feed for 2h per
animals to motion, but food deprivation itself day with exposure to motion on test days
also induced pica. OccWing just prior to the feeding session. CTA
This result is in conuast to data reported by was conducted using procedures described
Mitchell (1977). It should be noted, however, elsewhere (Fox & Daunton, 1982).
that studies showing pica in rats have used The mean daily consumption of food in the
experiment using off-vertical rotation is shown
intense motion stimuli (e.g., 75Qoo/s) or severe
gasmc irritants as inducing treatments. The in Figure 1. Food consumption increased and
body weight decreased over the initial days of
purpose of these preliminary studies in this
project was to investigate whether pica could be adaptation to the restricted feeding regimen (2
Wday) una intake stab%ed by about Day 11.
produced in rats using moderate motion
conditions that were representative of marments Using Day 19 (the day preceding exposure to
motion) as a baseline, anorexia was present on
known to produce motion sickness in man and
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 psc.001) but intake on Days 21 & 22 did not
differ from baseline (p.39). Body weight was
useful measure.
suppressed on each of the three days following
2. CTA. expasure to motion (ps<.003).
It has long been recognized that CTA can be The mean daily consumption of food in the
experiment using parabolic flight is shown in
produced by numerous interventions, including
motion, that are known to produce gastric Figure 2. Again, food consumption i n das
the animals adapted to the restricted feeding
distress in humans and animals. This
relationship between CTA and "internal mdaise” schedule (2 h/day) with body weight reflecting an
initial decrease (first 5 days) followed by a
has led to widespread interest in using CTA to
assess several forms of sickness arising from nonnal tendency to increase. On Day 12 the rats
gasmc disruption in animal models. Several were transported to the flight line and loaded on
observations have i n d i d t hat CTA may be a the airplane to determine whether this activity
useful measure of motion sickness in animal would affect the dependent measures. No effects
models. Important among these is the where seen on either food intake or body weight
demonstration that an intact vestibular system is with this procedure (Fcl). With Day 18 as a
4
baseline, anorexia was present immediately after
the flight (Day 19) and 48 h later (Day 20).
,
Food consumption 72 h after the flight did not
differ from that preceding the flight (p.80).
Food intake was suppressed immediately and 24 moderate stimulation that is
h following flight (ps<.002) but by 48 h after
the flight food intake did not differ from the
baseline (p>. 11 ).
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 Fiight groups did not roden that is of the
differ prior to the flight, but in the test following magn g in squirrel
parabolic animals in the Conaol group consumed monkeys, chimpanzees, and humans (Fox &
more fluid than did the animals in the Flight Daunton (1982); Fox et d., 1984). Further, this
group (p<.OOl). 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 d., 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 on severe mdcm 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-gravity 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 nstraint 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, crosscoupled control during passive motion is necessary if
stimulation that is very provocative for Rumans. 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 demonsmuon of
was absent after only 24 h. vomiting in cats and squirrel monkeys by visual
Informal observations regarding anorexia were stimulation alone (Daunton et ul., 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 squiml instances (e.g., "simulator siclmess), but this has
monkeys were repeatedly observed to eat the food 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 a few minutes (e.g., shown in this research that animals more prone
less than 5 min) 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 UnivexsaUy 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 P hyslQlOgy
this issue further.
1. Vasopressln.
Vasopressin (AVP) is elevated in humans
8. Effective Stimulus Parameters during nports of nawa and following vomiting
(see Fox, 1992 for a review). Plasma AVP is
The specific parameters of stimulation that dramatically eIevatcd in cats following vomiting
effectively produce motion sickness in animal but the resting level of AVP in blood plasma
5
does not differ among cats that are selected to be GABAergic terminals in the area postrema,
highly susceptible or very resistant to linear nucleus tractus solikus, 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 @'Ameli0 et
following motion sickness, but resting levels of 1988). In addition, the depletion of G
AVP in CSF are lower in animals that vomited immunoreactive in these areas after elec
during motion than in those animals which did stimulation of the vagus nerve seems to
not vomit (Fox er 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 mmpeptib.
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. W e co nducting 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 in different
et ol., 1988); (b) Neither CTA nor vomiting are species varied greatly. For example, linear
crucially dependent on the area postrema in either 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 is remarkably noneffective.
conmbuted 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 theories which include several additid this species.
brainstem and/or circumventricllal structures in Species 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 to make 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, 1990). In fact,
showing that the vagus nerve is crucial to CTA bothanecdomlandexperimentalevidenceindi~
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 program have 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 ul., 1987; Animal models will be crucial to the discovery
1988). and understanding of neurophysiological
mechanisms of these phenomena, but
4. irnmunocytochemlstry. considerable research will be required before
Preliminary evidence indicating a role for the answers come forth.
vagus nerve either in motion sickness or in
adaptation to stimuli producing motion sickness
has been shown. Using immunocytochemistry
we showed that the distribution pattern of
6
motor coordinati
111. CONCLUSIONS
All of the behavioral responses that have been
examined as measures of motion sickness in
animals are less than ideal. The only response
that is universally accepted as a valid measure is
vomiting. On initial consideration this appears lying down or going to sleep. In this regard it
to be a serious weakness in this area of research.
However, it should be recognized that no other
measures have been universally accepted for the
assessment of motion sickness in humans. The would suggest that motion
most commonly used additional measure in simply be an unfortunate ou
human studies is nausea, but the assessment of processes of adjusring the nwomuscular system
nausea, even in humans 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 in humans with only minimal success.
While we found some evidence for predictive
value in the level of AVP in CSF, this effect
was not highly predictive and significant work
would be required to understand this relationship
adequately. As is the case in humans, piasma
AVP was dramatically elevated in cats following
vomiting, but there was no evidence in this
research to indicate that the level of system A W
was predictive of susceptibility to motion
sichess.
It is now abundantly 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 is mediated via
circuitry in several circumventricular and
brainstem regions. Imporrant work remains to
provide understanding of the specific neural
mechanisms of the response that is so important
in disease and travel by modem conveyances.
A gend 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 postrema Aviation, Space and Environmental
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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.
Immunocytochemid localization of glutamic Neuroscience Abstracts, 8, 698.
acid decarboxylase (GAD) and substance P in
neural areas mediating motion-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 (Eds.). Basic and Canadian Journal Physiology and
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Racon: 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,
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H. (1985). Susceptibility of cat and squirrel applied aspects of vestibular
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stimulation: Correlation with susceptibility to University Press.
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University Press.
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Are nonemetic species an appropriate choice?
The Physiologist, 28, S61-562.
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