SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
This article presents the concept of a spatial orientation/motion perceptual system, the contributions of the vestibular receptors to this system, and apparatus and training procedures and observations to allow astronauts to preadapt to weightlessness. The author also discusses perceptual reactions to prolonged weightlessness.
Fundamental approaches in selection of new agents for evaluation in prevention of space/motion sickness (SMS) are reviewed. The discussion centers on drugs under investigation at the Johnson Space Center. Methodology that employs the rotating chair for measuring SMS symptomatology and susceptibility is described. The most obvious approach to the development of new agents relies on selection of agents from drug classes that possess pharmacologic properties of established anti-motion sickness agents. A second approach selects drugs that are used to prevent emesis caused by means other than exposure to motion. The third approach relies on basic research that characterizes individual differences in susceptibility. The hypothesis is: detection of individual differences leads to identification of specific drugs, which target physiologic systems that show individual differences. These physiologic systems are targets for therapy and may play a role in the etiology of SMS. Two drugs that reduce susceptibility to SMS include dexamethasone and d(CH2)5Tyr(Me)AVP, a vasopressin (AVP)V1 antagonist. The latter peptide has demonstrated complete blockade of emesis and other significant symptoms in squirrel monkeys. These studies were predicated on observations that subjects who were more resistant to SMS had higher plasma AVP after severe nausea than subjects with lower resistances. Investigations are underway to test a 0.5-mg intravenous dose in humans. Kappa opioid agonists inhibit AVP release and offer new therapeutic possibilities and advantages over AVP peptides. This review details the experimental data collected on AVP and adrenocorticotropin. The literature supports interrelated roles for AVP and opioid peptides in SMS. Experimental testing of kappa agonists is warranted because specific opioid agonists act at neuroanatomical sites causing nausea and vomiting. It is argued opioid receptors in the chemoreceptor trigger zone and vomiting center stimulate and inhibit the emetic response, respectively. The evidence suggests kappa and/or mu receptors at VC are involved in inhibition of emesis, whereas delta opioid receptors at CTZ are involved in stimulation of emesis.
We investigated the dynamic properties of the human vestibulo-ocular reflex (VOR) during roll head rotations in three human subjects using the magnetic search coil technique. In the first of two experiments, we quantify the behavior of the ocular motor plant in the torsional plane. The subject's eye was mechanically displaced into intorsion, extorsion or abduction, and the dynamic course of return of the eye to its resting position was measured. The mean predominant time constants of return were 210 msec from intorsion, 83 msec from extorsion, and 217 msec from abduction, although there was considerable variability of results from different trials and subjects. In the second experiment, we quantify the efficacy of velocity-to-position integration of the vestibular signal. Position-step stimuli were used to test the torsional or horizontal VOR, being applied with subjects heads erect or supine. After a torsional position-step, the eye drifted back to its resting position, but after a horizontal position-step the eye held its new horizontal position. To interpret these responses we used a simple model of the VOR with parameters of the ocular motor plant set to values determined during Exp 1. The time constant of the velocity-to-position neural integrator was smaller (typically 2 sec) in the torsional plane than in the horizontal plane (> 20 sec). No disconjugacy of torsional eye movements was observed. Thus, the dynamic properties of the VOR in roll differ significantly from those of the VOR in yaw, reflecting different visual demands placed on this reflex in these two planes.
5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.
Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.
We investigated the pathogenesis of acquired pendular nystagmus (APN) in six patients, three of whom had multiple sclerosis. First, we tested the hypothesis that the oscillations of APN are due to a delay in visual feedback secondary, for example, to demyelination of the optic nerves. We manipulated the latency to onset of visually guided eye movements using an electronic technique that induces sinusoidal oscillations in normal subjects. This manipulation did not change the characteristics of the APN, but did superimpose lower-frequency oscillations similar to those induced in normal subjects. These results are consistent with current models for smooth (non-saccadic) eye movements, which predict that prolongation of visual feedback could not account for the high-frequency oscillations that often characterize APN. Secondly, we attempted to determine whether an increase in the gain of the visually-enhanced vestibulo-ocular reflex (VOR), produced by viewing a near target, was accompanied by a commensurate increase in the amplitude of APN. Increases in horizontal or vertical VOR gain during near viewing occurred in four patients, but only two of them showed a parallel increase in APN amplitude. On the other hand, APN amplitude decreased during viewing of the near target in the two patients who showed no change in VOR gain. Taken together, these data suggest that neither delayed visual feedback nor a disorder of central vestibular mechanisms is primarily responsible for APN. More likely, these ocular oscillations are produced by abnormalities of internal feedback circuits, such as the reciprocal connections between brainstem nuclei and cerebellum.
Explore the source record for details and available documents.
The present study focused on the development of a procedure to assess perceived self-motion induced by visual surround motion--vection. Using an apparatus that permitted independent control of visual and inertial stimuli, prone observers were translated along their head x-axis (fore/aft). The observers' task was to report the direction of self-motion during passive forward and backward translations of their bodies coupled with exposure to various visual surround conditions. The proportion of "forward" responses was used to calculate each observer's point of subjective equality (PSE) for each surround condition. The results showed that the moving visual stimulus produced a significant shift in the PSE when data from the moving surround condition were compared with the stationary surround and no-vision condition. Further, the results indicated that vection increased monotonically with surround velocities between 4 and 40 degrees/sec. It was concluded that linear vection can be measured in terms of changes in the amplitude of whole-body inertial acceleration required to elicit equivalent numbers of "forward" and "backward" self-motion reports.
In two experiments, we used an ISCAN infrared video system to examine the influence of a pitched visual array on gaze elevation and on judgments of visually perceived eye level. In Experiment 1, subjects attempted to direct their gaze to a relaxed or to a horizontal orientation while they were seated in a room whose walls were pitched at various angles with respect to gravity. Gaze elevation was biased in the direction in which the room was pitched. In Experiment 2, subjects looked into a small box that was pitched at various angles while they attempted simply to direct their gaze alone, or to direct their gaze and place a visual target at their apparent horizon. Both gaze elevation and target settings varied systematically with the pitch orientation of the box. Our results suggest that under these conditions, an optostatic response, of which the subject is unaware, is responsible for the changes in both gaze elevation and judgments of target elevation.
The hypothesis of asymmetric otolith function asserts that physiological or anatomical differences in the two sides of the bilateral gravity-sensing otolith apparatus of the inner ear may be well compensated on Earth, but when exposed to novel gravitational states, the prior compensatory stratagems may be ineffective, leading to unstable vestibular responses and causing the phenomenon of space motion sickness. To investigate this hypothesis, spontaneous eye torsion, a reflex governed by the otolith organs, was examined in the upright position during the hypo- and hypergravity of parabolic flight aboard NASA's KC-135 aircraft in nine former astronauts whose history of space motion sickness was revealed after data analysis had been completed. Results showed that astronauts who had been sick in space had significantly higher scores of disconjugate eye torsion in parabolic flight, and that their responses were consistently different in 1.8 G relative to 0 G compared to astronauts who had not been sick in space. In 1 G, there were no differences in disconjugate eye torsion between the subjects. The results support the asymmetry hypothesis and offer a possible predictive test of space motion sickness.
Tests of the perception and use of linear acceleration sensory information were performed on the science crews of the Spacelab 1 (SL-1) and D-1 missions using linear "sleds" in-flight (D-1) and pre-post flight. The time delay between the acceleration step stimulus and the subjective response was consistently reduced during weightlessness, but was neither statistically significant nor of functional importance. Increased variability of responses when going from one environment to the other was apparent from measurements on the first day of the mission and in the first days post-flight. Subjective report of perceived motion during sinusoidal oscillation in weightlessness were qualitatively similar to reports on earth. In a closed-loop motion nulling task, enhanced performance was observed post-flight in all crewmembers tested in the Y or Z axes.
Inherent asymmetries of the gravity-sensitive otolith organs of the inner ear may be well-compensated in ordinary 1 G, but rendered unstable in novel gravitational states. Several aspects of ocular counterrolling and spontaneous eye torsion, reflexes governed by the otoliths, were examined during the hypo- and hypergravity in parabolic flight on the NASA KC-135 aircraft. Among the subjects were two astronauts, one who had suffered space motion sickness during his mission and one who had not. Using an observed separation of scores of torsional instability at 0 G as the criterion, we divided our 10 subjects into the 5 highest and 5 lowest scorers, reminiscent of the approximately 50% who do and the 50% who do not experience space motion sickness (SMS). The astronaut who had had SMS was in the high group; and the one who had not was in the low group. At 1.8 G, the groups defined at 0 G were significantly different in the instability measure. They were also significantly different at both 0 G and 1.8 G in another measure, that of torsional variability. There were no differences between the groups in amplitude of eye torsion in 0 G or 1.8 G. None of the tests were significantly different in 1 G. The results suggest that these tests of eye torsion on the KC-135 might differentiate those who would experience SMS from those who would not. Proof of this speculation awaits replication of the study using only astronaut subjects.
Tests of the perception and use of linear acceleration sensory information were performed on the science crews of the Spacelab 1 (SL-1) and D-1 missions using linear "sleds" in-flight (D-1) and pre-post flight. The time delay between the acceleration step stimulus and the subjective response was consistently reduced during weightlessness, but was neither statistically significant nor of functional importance. Increased variability of responses when going from one environment to the other was apparent from measurements on the first day of the mission and in the first days post-flight. Subjective reports of perceived motion during sinusoidal oscillation in weightlessness were qualitatively similar to reports on earth. In a closed-loop motion nulling task, enhanced performance was observed post-flight in all crewmembers tested in the Y or Z axes.
Visually-induced self-motion sensation and postural reflexes were first explored in microgravity on the Spacelab 1 mission where four subjects demonstrated that visual orientation effects were stronger in microgravity than preflight. Extended testing of two more subjects during the Spacelab D-1 orbital flight confirmed this finding. The development of visual substitution for inappropriate graviceptor information occurs over the first day or two in microgravity. Additional instrumentation to measure postural reactions failed to produce a more reliable indicator of visual effects than subjective orientation. Localized tactile cues applied to the feet changed the qualitative nature of vection and reduced its subjective strength.
Compensatory vertical eye movement gain (CVEMG) was recorded during pitch oscillation in darkness before, during and immediately after exposures to the stimulus rearrangement produced by the Preflight Adaptation Trainer (PAT) Tilt-Translation Device (TTD). The TTD is designed to elicit adaptive responses that are similar to those observed in microgravity-adapted astronauts. The data from Experiment 1 yielded a statistically significant CVEMG decrease following 15 min of exposure to a stimulus rearrangement condition where the phase angle between subject pitch tilt and visual scene translation was 270 degrees; statistically significant gain decreases were not observed following exposures either to a condition where the phase angle between subject pitch and scene translation was 90 degrees or to a no-stimulus-rearrangement condition. Experiment 2 replicated the 270 degrees-phase condition from Experiment 1 and extended the exposure duration from 30 to 45 min. Statistically significant additional changes in CVEMG associated with the increased exposure duration were not observed. The adaptation time constant estimated from the combined data from Experiments 1 and 2 was 29 min.
Little is known about the factors that control individual differences in susceptible to motion sickness. A serendipitous observation in our laboratory that most Chinese subjects become motion sick prompted this study. We used a rotating optokinetic drum to provoke motion sickness and compared gastric responses and symptom reports of Chinese, European-American, and African-American subjects. There was no difference in the responses of European-American and African-American subjects; however, Chinese subjects showed significantly greater disturbances in gastric activity and reported significantly more severe symptoms. We suggest that this hyper-susceptibility presents a natural model for the study of physiological mechanisms of nausea and other symptoms of motion sickness.
This experimentation defined a limited role for epinephrine in the autonomic nervous system function and the nausea that occurred following motion sickness testing. Individual responses to stressful sensory stimuli and nausea, as reflected by rising peripheral levels of epinephrine, were not significantly diminished upon repeated exposure and adaptation to the stressor. However, subjects who demonstrated more robust elevations of epinephrine in response to nausea displayed higher resistances to stressful motion stimuli. Modulation of peripheral catecholaminergic function with dexamethasone, or scopolamine plus amphetamine, suggested that altered autonomic nervous system function and nausea following motion sickness testing were not mediated by peripheral catecholamine receptor stimulation. Marked differences were noted in individual responses to drug and systemic responses of epinephrine and norepinephrine. It is possible that responses in epinephrine to motion sickness testing may predict resistance to stressful motion, and represent a peripheral manifestation of some as yet unknown central event of etiologic relevance.
Three-dimensional squirrel monkey eye movements were recorded during and immediately following rotation around an earth-vertical yaw axis (160 degrees/s steady state, 100 degrees/s2 acceleration and deceleration). To study interactions between the horizontal angular vestibulo-ocular reflex (VOR) and head orientation, postrotatory VOR alignment was changed relative to gravity by tilting the head out of the horizontal plane (pitch or roll tilt between 15 degrees and 90 degrees) immediately after cessation of motion. Results showed that in addition to post rotatory horizontal nystagmus, vertical nystagmus followed tilts to the left or right (roll), and torsional nystagmus followed forward or backward (pitch) tilts. When the time course and spatial orientation of eye velocity were considered in three dimensions, the axis of eye rotation always shifted toward alignment with gravity, and the postrotatory horizontal VOR decay was accelerated by the tilts. These phenomena may reflect a neural process that resolves the sensory conflict induced by this postrotatory tilt paradigm.