We have shown that overstimulation of the semicircular canals by rotation leads to decreased habituation to repetitive stimuli, as measured by the midlatency auditory evoked P50 potential, which may be at the root of a sensory gating deficit (an inability to appraise and filter out unwanted stimuli) present during SMS. In terms of alleviating the symptoms of rotation and the induced sensory gating deficit, our data in 72 subjects indicated scopolamine to be the countermeasure of choice. Scopolamine was the only countermeasure to effect a statistically significant mean change in duration of rotation compared to placebo (p<0.008), with >40% increase in rotation time. Results with promethazine, the current pharmacologic treatment for SMS, were not statistically significant, and meclizine and lorazepam were no more effective than placebo. Scopolamine by itself did not affect amplitude or habituation of P50 potential measures, suggesting that, at the dose used, scopolamine did not dysregulate RAS function to a significant level. However, scopolamine did lead to a lower decrease in habituation after rotation (~22%); in other words, scopolamine decreased the sensory gating deficit induced by rotation. Although this decrease was numerical and not statistically significant, it is indicative of a trend by scopolamine toward amelioration of the sensory gating deficit induced by rotation. The Operant Test Battery (OTB) indicated the Delayed Matching-to-Sample (DMTS) task, or short-term memory and attention task, to be the most sensitive measure of cognitive performance. The DMTS indicated SMS by itself had no discernible effects on accuracy or response rate and that, at the doses employed, the rank order of drugs with the best cognitive profiles are meclizine > scopolamine > promethazine > lorazepam. Work performed by our co-investigators at the Vestibular Function Laboratory in Antwerp using 3D oculography and unilateral centrifugation for otolith testing confirmed the ability of our paradigm to accurately assess the effects of countermeasures on the vestibular apparatus, from which the sensation of SMS may originate. These studies showed that the different components of the vestibular system (the semicircular canals vs. the otolith organs) react differently to the countermeasures and that scopolamine exclusively affected the utricular response, indicating a possible mechanism of action for scopolamine via a direct effect on the utricular system. The distribution of spin time frequencies among our study subject population (N=75) demonstrated that, in terms of the ability of our study subjects to tolerate induced SMS, the population had significant outliers. The majority of the study population exhibited a fairly low tolerance for induced SMS; however, there was a group of outliers who could spin significantly longer, appearing to have a predisposition to SMS tolerance. This novel finding, combined with results of off-axis rotation (see below), has been proposed for further examination as we study means of screening for SMS susceptibility and subsequent prophylaxis. As an extension of our NSBRI study, we attempted to assess the otolith organs using a new clinical paradigm involving off-axis rotation and measurement of the subjective visual vertical (SVV), the ability of an individual in darkness to adjust a luminous line to true vertical while at rest and during rotation. Clinical assessment of otolith organs is important to space medicine research due to the involvement of the utricle and saccule in SMS. Our objective was to assess otolith function in subjects with no vestibular complaints and in subjects with unilateral labyrinthine hypofunction. Subjects with no vestibular anomalies were able to set the SVV very close to vertical. However, certain subjects showed a mild asymmetry (vestibular dominance) of the otolith organs during on-axis rotation that was further accentuated during off-axis rotation. In the vestibular patients, the SVV deviated significantly toward the side of the lesion. Some subjects with dominant otolith organs were able to spin in the chair two and a half to three times longer than those without ear dominance, indicating less susceptibility to motion sickness. By screening for ear dominance using the SVV/rotational paradigm, pre-flight medication or compensation behaviors could be instituted in those individuals with an indicated susceptibility to SMS.

Jul-2003

New Orleans, Louisiana, Nov-2003

Daytona Beach, Florida, Feb-2003

Galveston, Texas, Jan-2003

Portland, Oregon, Oct-2002

New Orleans, Louisiana, Nov-2003