Treatment of motion sickness in parabolic flight with buccal scopolamine.

Treatment of acute motion sickness induced by parabolic flight with a preparation of scopolamine placed in the buccal pouch was investigated. Twenty-one subjects flew aboard a KC-135 aircraft operated by the National Aeronautics and Space Administration (NASA) which performed parabolic maneuvers resulting in periods of 0-g, 1-g, and 1.8-g. Each subject flew once with a tablet containing scopolamine and once with a placebo in a random order, crossover design. Signs and symptoms of motion sickness were systematically recorded during each parabola by an investigator who was blind to the content of the tablet. Compared with flights using placebo, flights with buccal scopolamine resulted in significantly lower scores for nausea (31%-35% reduction) and vomiting (50% reduction in number of parabolas with vomiting). Side effects of the drug during flight were negligible. We conclude that buccal scopolamine is more effective than a placebo in treating ongoing motion sickness.     

Vestibulo-spinal response modification as determined with the H-reflex during the Spacelab-1 flight

Summary Our laboratory at the Johnson Space Center has employed the H-reflex recorded from the soleus muscle as a method of monosynaptic reflex testing in conjunction with vertical linear acceleration to assess modification of utriculo-saccular function induced through prolonged exposure to microgravity. It was hypothesized that exposure to free fall would reduce the necessity for postural reflexes in the major leg muscles, and that postural modification would reflect a change, not in the peripheral vestibular organs, but more centrally. This postural adjustment would reflect a sensory motor rearrangement where otolith receptor input was reinterpreted to provide an environmentally appropriate response. In addition to the H-reflex (which was the only inflight measurement), vestibulo-spinal EMG from the gastrocnemius, and self-motion reports were obtained in response to a sudden earth vertical fall. Preflight, inflight and postflight motion sickness reports were also recorded, and related to the H-reflex data. The results indicated that early inflight H-reflex amplitude was similar to that recorded preflight, but that measurements obtained later in the flight (day seven) did not show a change in potentiation as a function of the different drop to shock intervals. Immediate postflight H-reflex response in three of the four astronauts tested showed a rebound effect. Postflight gastrocnemius EMG in response to the sudden fall did not show a significant change from preflight values. However, one crewman who was tested early postflight did show an increase in EMG activity in response to the sudden fall. This immediate postflight effect returned to baseline rapidly. Self-motion perception obtained inflight suggested that the early inflight drops were perceived like those preflight. Drops later inflight were described as sudden, fast, hard and translational in nature. Immediately postflight the drops were perceived like those late inflight, and the astronauts said that they did not feel as though they were falling, rather the floor came up to meet them. Post hoc peak H-reflex amplitude, both preflight and postflight was related to inflight space motion sickness.     

Lack of effects of astemizole on vestibular ocular reflex, motion sickness, and cognitive performance in man

Astemizole was orally administered to 20 subjects in a randomized, double-blind design to assess the efficacy of this peripherally active antihistamine as an antimotion sickness drug possessing no central side-effects. Measures of vestibular ocular reflex (VOR) were made to evaluate the agent as a selective vestibular depressant. Following 1 week of orally administered astemizole (30 mg daily), a Staircase Profile Test, a VOR test, and a variety of tests of cognitive performance were administered. These tests revealed no statistically significant effects of astemizole. This leads us to conclude that, although the drug probably reaches the peripheral vestibular apparatus in man by crossing the blood-vestibular barrier, a selective peripheral antihistamine (H1) action is inadequate to control motion sickness induced through cross-coupled accelerative semicircular canal stimulation in a rotating chair.     

Motion sickness: a modulatory role for the central cholinergic nervous system

The present review has extended the general theory of motion sickness proposed by Wood and Graybiel [135, 136] by identifying specific neurophysiological mechanisms that are involved in motion sickness and by interpreting the actions of both scopolamine and amphetamine as effective anti-motion sickness drugs within this neurophysiological context. The neurochemical and neurophysiological effects of scopolamine have been reviewed in relationship to central cholinergic pathways. Cholinergic pathways have been associated with both the perception and expression of normal and excessive levels of motion stimuli. New approaches to the problem of the prevention of motion sickness have been considered. Efferent nicotinic innervation at the primary sensory hair cells and the medial vestibular nucleus were identified as sites where modulation by cholinergic drugs might exert a beneficial influence. However, it was generally conceded that the complexity of the cholinergic system and the interaction of scopolamine with that system left open the possibility that pharmacological doses of drugs specific to the cholinergic system might exert significant modulatory influences at alternative sites, as well.     

Effect of amphetamine on optokinetically evoked head and eye movements in the squirrel monkey

The effect of amphetamine sulfate injection on head and eye movements evoked by optokinetic stimulus was studied in squirrel monkeys. No change was found in the gain of optokinetic-oculomotor and optokinetic-caputomotor functions, even after the maximum dose (0.5 mg/kg) of amphetamine. Also, no change in eye-head coordination was found. However, amphetamine facilitated the frequency of head nystagmus, whereas that of eye nystagmus did not change. When the poststimulus responses were studied in the dark, both nystagmoid head movement and optokinetic after eye nystagmus showed first phase and second phase. A different effect was found in the duration of these two phases suggesting the existence of distinct generators. Moreover, the synchronized onsets of head and eye nystagmus in both phases, and synchronized occurrence of quick phases indicated the existence of shared neural circuitry between head and eye movements.     

Transdermal scopolamine in the prevention of motion sickness: evaluation of the time course of efficacy

This study evaluated the time course of efficacy of transdermal scopolamine in the prevention of motion sickness induced by exposure to coriolis stimulation in a rotating chair. We measured levels of efficacy, quantified side effects and symptoms, and determined inter- and intra-subject variability following use of transdermal scopolamine. The response to transdermal scopolamine was highly variable, although overall we recorded a 40% improvement (p less than 0.05) in test scores 16-72 h after application of the transdermal system. This variability could not be explained solely by the levels of scopolamine present in the blood. The improvement was not due to the artifactual repression by scopolamine of selected symptoms of motion sickness. An unexpectedly high incidence of side effects was reported. It was concluded that the therapeutic use of transdermal scopolamine be evaluated individually and that individuals be cautioned that subsequent usage may not always be effective.     

Dynamic posture analysis of Spacelab-1 crew members

Summary Dynamic posture testing was conducted on the science crew of the Spacelab-1 mission on a single axis linear motion platform. Tests took place in pre- and post-flight sessions lasting approximately 20 min each. The pre-flight tests were widely spaced over the several months prior to the mission while the post-flight tests were conducted over the first, second, fourth, and sixth days after landing. Two of the crew members were also tested on the day of landing. Consistent with previous postural testing conducted on flight crews, these crew members were able to complete simple postural tasks to an acceptable level even in the first few hours after landing. Our tests were designed to induce dynamic postural responses using a variety of stimuli and from these responses, evaluate subtle changes in the postural control system which had occurred over the duration of the flight. Periodic sampling post-flight allowed us to observe the time course of readaptation to terrestrial life. Our observations of hip and shoulder position, when subjected to careful analysis, indicated modification of the postural response from pre- to post-flight and that demonstrable adjustments in the dynamic control of their postural systems were taking place in the first few days after flight. For transient stimuli where the platform on which they were asked to stand quickly moved a few centimeters fore or aft then stopped, ballistic or open loop programs would closely characterize the response. During these responses the desired target position was not always achieved and of equal importance not always properly corrected some 15 seconds after the platform ceased to move. The persistent observation was that the subjects had a much stronger dependence on visual stabilization post-flight than pre-flight. This was best illustrated by a slow or only partial recovery to an upward posture after a transient base-of-support movement with eyes open. Postural responses to persistent wideband pseudorandom base-of-support translation stimuli were modeled as time invarient linear systems arrived at by Kaiman adaptive filter techniques. Derived model parame ters such as damping factor and fundamental frequency of the closed loop system showed significant modification between pre- and post-flight. This phenomenon is best characterized by movement of the poles toward increasing stability. While pre-flight data tended to show shoulders and hips moving in phase with each other, post-flight data showed a more disjoint behavior. One can speculate that this change illustrates a shattered postural organization or an acquired strategy not designed to stabilize terrestrial posture but as a carry over from optimum inflight postural control. Given our observations one can never be certain if these changes represent modifications in the physiology of posture of purposeful changes in strategy. As in other examples of motion behavior, the time domain analysis as represented by the step changes in position is not always reconcilable with the system modeling of pseudorandum responses and subsequent frequency domain analysis as represented by the pseudorandom noise stimuli. We present the observed data with arguments and some contradictions as to the nature of the adaptive changes which occur in the postural control system.     

Otolith tilt-translation reinterpretation following prolonged weightlessness: implications for preflight training

Observations with three astronauts yielded two major findings. First, perceived self-motion during sinusoidal roll differed immediately postflight from preflight. Between 70 and 150 min after landing, roll was perceived primarily as linear translation. Secondly, more horizontal eye movement was elicited by roll stimulation immediately postflight relative to both preflight and later postflight observations. These results support an "otolith tilt-translation reinterpretation" hypothesis, which has clear implications for understanding astronaut reports of space motion sickness during the early period of orbital flight. A proposal for "prophylactic adaptation training" which may provide preflight adaptation to weightlessness, derives from this research.     

Effect of otolith end organ ablation on horizontal optokinetic nystagmus, and optokinetic afternystagmus in the squirrel monkey.

Horizontal optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN) (stimulus speed 0-200 degrees/sec with 1 degree/sec constant angular acceleration) were examined before and after utriculo-sacculectomy (bilateral, two-stage) in squirrel monkeys. OKN exhibited a slight decline only after bilateral otolith and organ ablations. OKAN showed a minimal decline after unilateral operation but no change after bilateral operations. Severe OKN reduction and disappearance of OKAN after bilateral labyrinthectomy in primates should basically reflect the elimination of inputs from the cristae ampullares, and not from the maculae.     

Vestibular-visual conflict sickness in the squirrel monkey

When combined vestibular and visual (optokinetic) stimuli were given to squirrel monkeys in a direction and phase mismatching sinusoidal mode (in yaw plane), five of six monkeys exhibited actual emesis during three repeated exposures on separate trial days. Two animals vomited on two trial days and three animals, on one day. The incidence took place in 38.9% of the total trial days. When the identical vestibular and visual stimuli were given individually, the effect was negligible, thus confirming each stimulus magnitude was not stressful enough to produce emesis when used separately.