Specific Aims: The original specific aims for this project were: SA1) Demonstrate that individual differences exist in the ability to adapt to gravitational transitions, and can be measured quantitatively by measures of subjective orientation, closed loop manual control, and subjective motions sickness reports. SA2) Test whether pre-training by adapting to one altered gravity environment can improve sensorimotor adaptation in another altered gravity environment. SA3) Test whether the leading pharmacological agent, promethazine, affects either basic vestibular perceptual function or the adaptation rate to an altered gravity environment and the associated motion sickness symptoms. SA4) Develop and test a combined pre-adaptation training and pharmacological intervention protocol that can both improve sensorimotor adaptation and reduce the associated motion sickness.

Hypotheses: The hypotheses are: H1) Individual differences exist in the ability to adapt to altered gravity environments and these differences can be predicted by measuring adaptability in one altered gravity environment. H2) Pre-adaptation training in one altered gravity environment will improve sensorimotor adaptation in another altered gravity environment. H3) Promethazine will reduce motion sickness, but will have no influence on either basic vestibular perceptual function or sensorimotor adaptation to altered gravity environments.

Results: We determine individual differences in performance of both the perception and manual control tasks in terms of initial performance decrement and adaptation time constant. All subjects consistently show a performance decrement in the perception and closed-loop manual control task on initial exposure to altered-gravity, followed by a return back to baseline performance. Promethazine significantly affects upright roll tilt motion perception thresholds, a measure of basic vestibular perceptual function. Thresholds were not different with promethazine for upright yaw or upright interaural translation motions. However, the small but consistent effect of promethazine on roll tilt perception could have functional and operational significance.

Deliverables: Deliverables are a methodology for measuring an individual's capacity to adapt to an altered gravity environment using affordable centrifuge tests, and a combined pharmacological and pre-adaptation training intervention to reduce the severity of motion sickness and sensorimotor impairment during gravitational transitions.

We also developed, pilot tested, and conducted a full manual control experiment using a short radius centrifuge and a human in the loop feedback control system. We found that both the RMSE and variability in the nulled chair position increased when subjects transitioned into the hypo-gravity environment, representing a worsening in the ability to perceive and null out passive roll tilt motions. Metrics related to the control strategies of the subjects, such as operator gains and control lags are currently being examined. From this ongoing analysis we hope to provide insight into changes in operational control strategies between the various gravity conditions, results that should be relevant to piloting performance during human controlled flight.

The original specific aims and hypothesis for this project were:

SA1) Demonstrate that individual differences exist in the ability to adapt to gravitational transitions, and can be measured quantitatively by measures of subjective orientation, closed loop manual control, and subjective motions sickness reports. Data analysis shows individual differences in performance of both the perception and manual control task in terms of initial performance decrement and adaptation time constant. Apart from individual differences, subjects consistently show a performance decrement in the perception and closed-loop manual control task on initial exposure to altered-gravity, followed by a return back to baseline performance.

SA2) Test whether pre-training by adapting to one altered gravity environment can improve sensorimotor adaptation in another altered gravity environment.

SA3) Test whether the leading pharmacological agent, promethazine, affects either basic vestibular perceptual function or the adaptation rate to an altered gravity environment and the associated motion sickness symptoms. To date, one important finding is that promethazine has a small but significant effect on upright roll tilt motion perception thresholds, a measure of basic vestibular perceptual function. Thresholds were not different with promethazine for upright yaw or upright interaural translation motions. The small but consistent effect of promethazine on roll tilt perception could have functional and operational significance.

SA4) Develop and test a combined pre-adaptation training and pharmacological intervention protocol that can both improve sensorimotor adaptation and reduce the associate motion sickness. The hypotheses are: H1) Individual differences exist in the ability to adapt to altered gravity environments and these differences can be predicted by measuring adaptability in one altered gravity environment. H2) Pre-adaptation training in one altered gravity environment will improve sensorimotor adaptation in another altered gravity environment. H3) Promethazine will reduce motion sickness, but will have no influence on either basic vestibular perceptual function or sensorimotor adaptation to altered gravity environments.

Deliverables include a methodology for measuring an individual's capacity to adapt to an altered gravity environment using affordable centrifuge tests, and a combined pharmacological and pre-adaptation training intervention to reduce the severity of motion sickness and sensorimotor impairment during gravitational transitions.

Using a short radius centrifuge, we created a land-based hypo-gravity analog test paradigm. We developed the test protocol, conducted pilot testing, and tested 10 subjects in our altered-gravity perception test protocol. Analysis to date has revealed that subjects underestimate their roll tilts when put into hypo-gravity compared to their baseline 1 G perception (mean gain diff = -0.27, p=0.006). After approximately 45 minutes in the hypo-gravity environment, subjects' motion perception returned to their 1 G baseline showing that subjects were able to adapt to the altered-gravity environment. Data analysis is currently being finalized and preparation of the associated manuscript is underway.

We also developed, pilot tested, and conducted a full manual control experiment using a short radius centrifuge and a human in the loop feedback control system. We have completed the majority of the data analysis for this study, and have found that both the RMSE and variability in the nulled chair position increased when subjects transitioned into the hypo-gravity environment, representing a worsening in the ability to perceive and null out passive roll tilt motions. Metrics related to the control strategies of the subjects, such as operator gains and control lags are currently being examined. From this ongoing analysis we hope to provide insight into changes in operational control strategies between the various gravity conditions, results that should be relevant to piloting performance during human controlled flight.

Finally, we collected additional motion threshold data from subjects who were involved in our centrifugation studies. With this additional data, we were able to make statistical comparisons between basic vestibular function as estimated by motion thresholds and functional control in altered-gravity environments, as described by various metrics of manual control ability. We have completed data analysis for this study and found a positive, linear correlation between manual control variability and vestibular thresholds (p < 0.01) in the 1.0 GZ baseline condition. This suggests that sensory precision is a limiting factor in manual control performance. Additionally, manual control performance was 12.7% lower in 1.33 GZ (p < 0.05) and 37.5% higher in 0.5 GZ (p < 0.05), as compared to 1 GZ. Preparation of the associated manuscript is underway.

The specific aims and hypothesis for this project are:

SA1) Demonstrate that individual differences exist in the ability to adapt to gravitational transitions, and can be measured quantitatively by measures of subjective orientation, closed loop manual control, and subjective motions sickness reports. Preliminary data analysis show individual differences in performance of the manual control task in terms of initial performance decrement and adaptation time constant. Apart from individual differences, subjects consistently show a performance decrement in the closed-loop manual control task on initial exposure to altered-gravity, followed by an performance return back to baseline performance.

SA2) Test whether pre-training by adapting to one altered gravity environment can improve sensorimotor adaptation in another altered gravity environment.

SA3) Test whether the leading pharmacological agent, promethazine, affects either basic vestibular perceptual function or the adaptation rate to an altered gravity environment and the associated motion sickness symptoms.

SA4) Develop and test a combined pre-adaptation training and pharmacological intervention protocol that can both improve sensorimotor adaptation and reduce the associate motion sickness.

The hypotheses are: H1) Individual differences exist in the ability to adapt to altered gravity environments and these differences can be predicted by measuring adaptability in one altered gravity environment. H2) Pre-adaptation training in one altered gravity environment will improve sensorimotor adaptation in another altered gravity environment. H3) Promethazine will reduce motion sickness, but will have no influence on either basic vestibular perceptual function or sensorimotor adaptation to altered gravity environments.

To date, one important finding is that promethazine has little effect on vestibular perceptual function. This is important because it eliminates a possible confound in our ongoing adaptation experiments. Deliverables include a methodology for measuring an individual's capacity to adapt to an altered gravity environment using affordable centrifuge tests, and a combined pharmacological and pre-adaptation training intervention to reduce the severity of motion sickness and sensorimotor impairment during gravitational transitions.

Refined Perception and Manual Control Measurement Methodologies and Optimized Experiment Design: The measures of adaptation that will be used have been finalized to include a roll tilt perception, manual control task, and subjective reports of motion sickness. Roll tilt perception will be measured from the orientation of a haptic indicator during static and dynamic tilts. The manual control task will be a closed loop task in which the subjects will use the indicator bar to maintain an upright orientation in response to a pseudo-random roll tilt disturbance. Human subject pilot testing of both of these tasks (upright and supine) has been used to investigate and resolve practical implementation issues as well as to inform the simulation tool. Informed by pilot data, the simulation tool allows us to explore where improvements can be made in experiment parameters such as length, profile tilt angles, static and continuous tilt time, and frequency of subject reports.

Hardware/Software Development: A considerable effort has focused on software and hardware development necessary for our planned experiments. The chair on the centrifuge, which was originally in the upright position, has been moved into the supine position, as it should be to allow for our designed altered gravity levels in our future experiments. During safety testing, we were faced with an unexpected issue with the centrifuge concerning a position control error. This problem delayed our progress but the entire team worked to resolve the issue. We were able to complete extensive human subject safety testing for the device and we are now quickly moving forward with testing and data collection.

Exercise and Artificial Gravity (AG): Graduate student, Ana Diaz, completed her PhD thesis investigating the combination of exercise and centrifugation. This research was inspired by the AGREE proposal, which intended to construct a short-radius centrifuge in an International Space Station (ISS) module. Subjects were tested with 3 different levels of AG and ergometer exercise. Results were used to modify and refine a cardiovascular model that captured the transient hemodynamic responses to exercise under AG.

The specific aims and hypothesis for this project are: SA1) Demonstrate that individual differences exist in the ability to adapt to gravitational transitions, and can be measured quantitatively by measures of subjective orientation, closed loop manual control, and subjective motions sickness reports. Preliminary data analysis show individual differences in performance of the manual control task in terms of initial performance decrement and adaptation time constant. Apart from individual differences, subjects consistently show a performance decrement in the closed-loop manual control task on initial exposure to altered-gravity, followed by an performance return back to baseline performance.

SA2) Test whether pre-training by adapting to one altered gravity environment can improve sensorimotor adaptation in another altered gravity environment.

SA3) Test whether the leading pharmacological agent, promethazine, affects either basic vestibular perceptual function or the adaptation rate to an altered gravity environment and the associated motion sickness symptoms.

SA4) Develop and test a combined pre-adaptation training and pharmacological intervention protocol that can both improve sensorimotor adaptation and reduce the associate motion sickness.

The hypotheses are: H1) Individual differences exist in the ability to adapt to altered gravity environments and these differences can be predicted by measuring adaptability in one altered gravity environment. H2) Pre-adaptation training in one altered gravity environment will improve sensorimotor adaptation in another altered gravity environment. H3) Promethazine will reduce motion sickness, but will have no influence on either basic vestibular perceptual function or sensorimotor adaptation to altered gravity environments.

Deliverables include a methodology for measuring an individual's capacity to adapt to an altered gravity environment using affordable centrifuge tests, and a combined pharmacological and pre-adaptation training intervention to reduce the severity of motion sickness and sensorimotor impairment during gravitational transitions.

In Experiment 1 we aim to test whether an individual's adaptation rate in one altered gravity environment can be predicted by an individual's adaptation in a different gravity environment. For this purpose we will test if an individual's adaptation rate in -1.5 Gz (headward centrifugal force) will predict their adaptation rate in +1.5 Gz (footward centrifugal force). Since we expect adaptation to one environment to temporarily influence an individual's ability to adapt to other environments, we will separate these two adaptation conditions by at least six months.

In Experiment 2, we will test the hypothesis that pre-training by adapting to one altered gravity (-1.5 Gz) will temporarily enhance an individual's ability to adapt to another altered gravity environment (+1.5 Gz). For this purpose we will separate the pre-training and testing sessions by 1 week.

In Experiment 3 we will test the impact that promethazine has on basic vestibular function using perceptual thresholds, tilt perception, and manual control measures.

In Experiment 4, we will test whether promethazine influences adaptation to altered gravity. Specifically, we will study adaptation to a +1.5 Gz environment with and without promethazine application. We hypothesize that motion sickness will be reduced with promethazine, but that adaptation rate will be unaffected.

Finally in Experiment 5, we will combine the promethazine use with the pre-training countermeasure. We hypothesize that the combined intervention will result in reduced motion sickness and improved sensorimotor adaptation during adaptation to an altered gravity environment (+1.5 Gz).

A considerable effort has focused on software and hardware development to be used during the experiments. A key component for all experiments is a somatosensory joystick used to report the perceived tilt angle during experiments, as well as to do the manual control task. Furthermore, the centrifuge at Massachusetts Eye and Ear Infirmary (MEEI) is being modified to include this joystick, as well as to facilitate orienting the device in a supine mode.