NOTE: Project extended until 05/31/2008 per PI (3/08)

NOTE: Project extended until 03/31/2008 per PI (5/07)

Pre-/Postflight Only

In flight development phase (data collection has begun)

Our first specific aim is to examine adaptive changes in the spatial reference frame used for coding orientation and motion as a function of space flight. By examining the effects of head tilt on balance control, we will test our hypothesis that there is a reorientation of central vestibular processing from a gravitational frame of reference to a head frame of reference as a function of adaptation to microgravity. Our second specific aim is to examine the feasibility of altering the re-adaptation process following space flight by providing discordant canal-otolith-somatosensory stimuli using short-radius pitch centrifugation.

This study specifically addresses Neurovestibular Adaptation questions of the Critical Path Roadmap (CPR Risks 15 and 16) related to the physiological basis for disruption of balance control and spatial disorientation following g-transitions. Additional post-flight posturography measures obtained during this study will expand our existing database and increase our ability to predict recovery curves from mathematical models for individuals based on pre-flight postural performance. The incorporation of head tilts during posturography addresses our general hypothesis for the physiological basis for the disruption of balance control following g-transitions, and provides an enhanced technique to determine crew readiness to return to normal activities following return to Earth. The incorporation of short-radius centrifugation during the post-flight period addresses the ability of crewmembers to adapt to multiple gravitoinertial environments and switch between them, e.g., as required for intermittent exposure to artificial gravity. The results of this study will also assess the potential risk for disrupting the re-adaptation process by exposure to discordant sensory stimuli during low levels of centrifugation.

The ROC curve is a plot of sensitivity versus 1-specificity as the classification threshold changes. In particular the area under the ROC is a useful index for evaluating the inputs to the classifier. In our case, we evaluated the individual test conditions used to distinguish astronauts from controls on landing day in terms of their respective ROC areas. A rough guide to interpreting the area under the curve is the traditional academic point system: 0.90-1.0 = excellent; 0.80-0.90 = good; 0.70-0.80 = fair; 0.60-0.70 = poor; 0.50-0.60 = fail. Sensitivities and specificities were used to determine optimal thresholds for assessing postural stability recovery.

The area under the ROC curve was 0.77 (fair) for the standard eyes-closed fixed-support Romberg test, improving to 0.86 (good) with head movements. With the unstable support, however, post-flight performance was so degraded that for a range of thresholds, astronauts could be completely distinguished from controls, with or without head movements (ROC area = 1.0). In situations, where the ROC area is less than 1.0, it is desirable to choose a threshold that gives high sensitivity at the expense of lower specificity so that astronauts who have not recovered will almost certainly be identified. For example, when using the eyes-closed fixed-support Romberg test with head movements, one might use the threshold that gives a sensitivity of 0.91 and a specificity of 0.64. By comparison, increased specificity (91% of recovered astronauts, identified), but with sensitivity dropping to 0.82 (18% of non-recovered astronauts erroneously classified as recovered). A more conservative threshold can be used to correctly classify all astronauts at 100% test sensitivity, but with only 18% specificity (orange circled point). Thus using the ROC curve, one can make a ready evaluation of test sensitivity and specificity providing an evidence-base for assessing post-flight recovery.

ROC areas for the classifiers were derived from the same data used to estimate them (only 22 subjects). As a result, when applying the classifier to EQ scores from future missions the actual ROC areas would be expected to be somewhat lower. To obtain a more realistic prediction of the sensitivity and specificity for this classifier, Bayesian analysis was used to estimate the statistical model for EQ scores. This model was then used to simulate data that could be plausibly obtained from 1000 additional subjects. Values of predicted sensitivity and specificity obtained by classifying the simulated data were 0.943 and 0.973 (as opposed to both being 1.0 as estimated from the original data). For the unstable platform without head movements, even though the ROC area was 1.0 for the sample of 22 subjects, the simulation-predicted sensitivity and specificity were 0.918 and 0.734, both considerably lower than for the analogous test with head movements.

Pre-/Postflight Only In flight development phase (data collection has begun)

Our first specific aim is to examine adaptive changes in the spatial reference frame used for coding orientation and motion as a function of space flight. By examining the effects of head tilt on balance control, we will test our hypothesis that there is a reorientation of central vestibular processing from a gravitational frame of reference to a head frame of reference as a function of adaptation to microgravity. Our second specific aim is to examine the feasibility of altering the re-adaptation process following space flight by providing discordant canal-otolith-somatosensory stimuli using short-radius pitch centrifugation.

This study specifically addresses Neurovestibular Adaptation questions of the Critical Path Roadmap (CPR Risks 15 and 16) related to the physiological basis for disruption of balance control and spatial disorientation following g-transitions. Additional post-flight posturography measures obtained during this study will expand our existing database and increase our ability to predict recovery curves from mathematical models for individuals based on pre-flight postural performance. The incorporation of head tilts during posturography addresses our general hypothesis for the physiological basis for the disruption of balance control following g-transitions, and provides an enhanced technique to determine crew readiness to return to normal activities following return to Earth. The incorporation of short-radius centrifugation during the post-flight period addresses the ability of crewmembers to adapt to multiple gravitoinertial environments and switch between them, e.g., as required for intermittent exposure to artificial gravity. The results of this study will also assess the potential risk for disrupting the re-adaptation process by exposure to discordant sensory stimuli during low levels of centrifugation.

Preliminary findings: During pre-flight testing all subjects adequately compensated for different head orientations with respect to gravity during eyes-closed, fixed-support conditions (SOT-2). Consistent with the results from our previous normative study (Paloski et al., Gait & Posture 23: 315-23, 2006), postural stability was decreased during dynamic head tilts with eyes-closed and sway-referenced support (SOT-5). Postural sway occurred primarily in the anterior-posterior (AP) direction versus medial-lateral (ML).

Postural stability was decreased on R+0 for all conditions with absent vision and altered proprioceptive feedback (SOT-5). The performance decrements on trials requiring dynamic head movements were most striking: all eleven subjects fell on at least one SOT-5 “Dynamic” trial on R+0, suggesting that this stability threatening condition should be avoided by crewmembers during normal daily activities. It is perhaps equally important to note how the same head tilt conditions using a fixed support (SOT-2) failed to detected the sensorimotor change, especially since this is the typical paradigm used clinically (Romberg test). Performance recovery for head erect conditions followed similar trajectories to those previously reported by our laboratory. Static and dynamic head tilt trials had similar recovery time constants as head erect, but at lower performance levels.

Our second specific aim is to examine the feasibility of altering the re-adaptation process following space flight by providing discordant canal-otolith-somatosensory stimuli using short-radius pitch axis centrifugation. There were no significant differences between pre-SAC and post-SAC measures. There were also no significant differences between L-30 and R+3 sessions in motion perception reports and eye movements during centrifugation.

Conclusions: The highly disrupted balance control performance during head tilts after flight is consistent with our hypothesis that changes in the central nervous system processing of otolith information contributes to the disruption of balance control following g-transitions. Adding head movements to SOT 5 enhances the sensitivity of the balance control measures for astronauts, perhaps making it more functionally relevant test for this highly competitive subject group. Absence of similar findings for the static tilt conditions suggest that processing of dynamic canal-otolith afferent information is severely disrupted early after flight, but that this can be compensated for by limiting head movements. In addition, the absence of similar findings during dynamic head tilts on a fixed support surface indicates the use of somatosensory input to compensate for adaptive changes in vestibular function. Based on the results of this study, head tilts during posturography have been implemented as a medical requirement for functional neurological assessment following short- and long-duration space missions. The standard Romberg test would underestimate the deficits observed on the computerized sway-referenced platform.

While post-flight posture performance decrements have been reported following exposures to short-radius off-axis pitch rotation, limited exposure to similar pitch centrifugation profiles on R+3 (nominal return to duty day) did not substantially disrupt postural performance in this study. Further work will be required to identify the incidence and mechanisms responsible for the paroxysmal losses of spatial orientation following space flight known as “flashbacks.”

Our first specific aim is to examine adaptive changes in the spatial reference frame used for coding orientation and motion as a function of space flight. By examining the effects of head tilt on balance control, we will test our hypothesis that there is a reorientation of central vestibular processing from a gravitational frame of reference to a head frame of reference as a function of adaptation to microgravity. Our second specific aim is to examine the feasibility of altering the re-adaptation process following space flight by providing discordant canal-otolith-somatosensory stimuli using short-radius pitch centrifugation.

This study specifically addresses Neurovestibular Adaptation questions of the Critical Path Roadmap (CPR Risks 15 and 16) related to the physiological basis for disruption of balance control and spatial disorientation following g-transitions. Additional post-flight posturography measures obtained during this study will expand our existing database and increase our ability to predict recovery curves from mathematical models for individuals based on pre-flight postural performance. The incorporation of head tilts during posturography addresses our general hypothesis for the physiological basis for the disruption of balance control following g-transitions, and provides an enhanced technique to determine crew readiness to return to normal activities following return to Earth. The incorporation of short-radius centrifugation during the post-flight period addresses the ability of crewmembers to adapt to multiple gravitoinertial environments and switch between them, e.g., as required for intermittent exposure to artificial gravity. The results of this study will also assess the potential risk for disrupting the re-adaptation process by exposure to discordant sensory stimuli during low levels of centrifugation.

A manuscript describing the results from one of our normative studies was published in Gait and Posture (Paloski et al, 2006). This study was useful to optimize the astronaut posture protocol by: restricting head tilts to the pitch plane, limiting the frequency of the dynamic tilts to 0.33 Hz, reducing the amplitude of the tilts to 20° and performing statistical power analyses to determine the number of trials required for each condition. A second manuscript is in revision describing the results of a companion eccentric rotation study that was used to finalize the centrifuge protocol for Specific Aim 2 (Wood et al., 2006).

Pre- and Post-flight Measures – Specific Aim 1:

Our first specific aim is to examine adaptive changes in the spatial reference frame used for coding orientation and motion as a function of space flight. We predicted the use of a head spatial reference frame will be characterized by differences in the landing day measurements relative to those observed before flight. These include decreased postural stability as evidenced by increased sway amplitudes and decreased equilibrium scores, with greater differences between pre- and post-flight during head tilt conditions. Nine astronauts have completed this study to date. In this past reporting year, pre- and post-flight data was obtained on four additional participants from the STS-121 and STS-115 missions. We also resumed an ongoing normative study designed to obtain repeated postural measures in healthy age, gender and height-matched control subjects using the same timeline scheduling as their astronaut counterparts.

Pre-flight scores for head erect, forward, backward, and moving at 0.33 Hz in the pitch plane were all in the normal range of the performance distributions. Consistent with our previous post-flight studies, performance on landing day was substantially decreased for these conditions with absent visual and altered proprioceptive feedback. The most striking result on landing day; however, was on trials requiring active head movements at 0.33 Hz. On landing day, all nine subjects fell on at least one SOT-5 trial with active head movements (falls on 14 of 18 trials overall).

The recovery curves for these crewmembers for trials with head erect followed similar trajectories to previous astronaut data recorded by our laboratory. The recovery profile for trials with the head movements, in contrast, had a similar recovery time constant but at lower performance levels compared with the head erect trials.

Pre- and Postflight Measures – Specific Aim 2:

Our second specific aim is to examine the feasibility of altering the re-adaptation process following space flight by providing discordant canal-otolith-somatosensory stimuli using short-radius pitch axis centrifugation. The centrifuge profile utilized in this study represents a composite of different profiles that appeared to disrupt the recovery of one Spacelab astronaut as late as R+5 as described above. Although there were some interesting modulations of vertical and horizontal vergence eye movements during centrifugation, there were no apparent differences in these responses between pre- and post-flight. There were also no consistent differences between motion perception reports from pre- to post-flight. Of the 9 participants to date, the centrifugation did not substantially disrupt postural performance either pre- or post-flight.

These same twelve subjects also participated in a separate centrifuge control study during which the superimposed sinusoidal oscillation varied over this same frequency range. Eleven subjects were also oscillated at 0.14, 0.3, or 0.6 Hz without centrifugation with the interaural axis positioned either 0.5m off-axis and over the axis of rotation. The vertical eye velocity gains were more enhanced during off-axis rotation at lower frequencies, while differences in horizontal vergence in the dark were greater between on- and off-axis conditions at higher frequencies. During visual-vestibular interaction, the vertical gain was systematically enhanced during forward-facing rotation and suppressed during backward-facing rotation across frequencies. The upward bias velocity in the dark was significantly increased during the visual-vestibular interactions, more so in the forward-facing direction. Based on the results of this initial study, we elected to provide two runs for each centrifuge session incorporating oscillation at 0.33 Hz in both forward-facing and backward-facing directions.

Pre- and Postflight Measures – Specific Aim 1: Our first specific aim is to examine adaptive changes in the spatial reference frame used for coding orientation and motion as a function of space flight. We predicted the use of a head spatial reference frame will be characterized by differences in the landing day measurements relative to those observed before flight. These include decreased postural stability as evidenced by increased sway amplitudes and decreased equilibrium scores, with greater differences between pre- and post-flight during head tilt conditions. Five of ten astronauts have completed this study, and an ongoing normative study is obtaining repeated postural measures in healthy age, gender and height-matched control subjects using the same timeline scheduling as their astronaut counterparts.

Pre-flight scores to date for head erect, forward, backward, and moving at 0.33 Hz in the pitch plane were all in the upper range of the normative performance distributions. Consistent with our previous post-flight studies, performance on landing day was substantially decreased for conditions with absent visual and altered proprioceptive feedback. The most striking result on landing day; however, was on trials requiring active head movements at 0.33 Hz. All subjects fell on SOT-5 trials on landing day with active head movements (9 of 10 trials overall). The recovery curves for these crewmembers for trials with head erect followed similar trajectories to previous astronaut data recorded by our laboratory. The recovery profile for trials with the head movements, in contrast, had a similar recovery time constant but at significantly lower performance levels compared with the head erect trials. This decrease in performance during head tilts is consistent with our hypothesis that the physiological basis for disruption of balance control and spatial disorientation following g-transitions relates to a change in the reference frame used for central vestibular processing.

Pre- and Postflight Measures – Specific Aim 2: Our second specific aim is to examine the feasibility of altering the re-adaptation process following space flight by providing discordant canal-otolith-somatosensory stimuli using short-radius pitch axis centrifugation. The centrifuge profile utilized in this study represents a composite of different profiles that appeared to disrupt the recovery of one Spacelab astronaut as late as R+5 as described above. Although there were some interesting modulations of vertical and horizontal vergence eye movements during centrifugation, there were no apparent differences in these responses between pre- and post-flight. There were also no consistent differences between motion perception reports from pre- to post-flight. Although the postural performance following centrifugation was also not substantially changed in any of the five crewmembers tested to date in this study, this may reflect behavioral characteristics that contribute to the large inter-individual differences in neurovestibular symptoms. It is interesting to note that pre-flight scores of the five participants were all in the upper range of the normative performance distributions. The risk of centrifugation disrupting the re-adaptation process may be greater for individuals that score in the lower range of pre-flight performance distributions.

These same twelve subjects also participated in a separate centrifuge control study during which the superimposed sinusoidal oscillation varied over this same frequency range. Eleven subjects were also oscillated at 0.14, 0.3, or 0.6 Hz without centrifugation with the interaural axis positioned either 0.5m off-axis and over the axis of rotation. The vertical eye velocity gains were more enhanced during off-axis rotation at lower frequencies, while differences in horizontal vergence in the dark were greater between on- and off-axis conditions at higher frequencies. During visual-vestibular interaction, the vertical gain was systematically enhanced during forward-facing rotation and suppressed during backward-facing rotation across frequencies. The upward bias velocity in the dark was significantly increased during the visual-vestibular interactions, more so in the forward-facing direction. Based on the results of this initial study, we elected to provide two runs for each centrifuge session incorporating oscillation at 0.33 Hz in both forward-facing and backward-facing directions.

Pre- and Postflight Measures – Specific Aim 1: Our first specific aim is to examine adaptive changes in the spatial reference frame used for coding orientation and motion as a function of space flight. We predicted the use of a head spatial reference frame will be characterized by differences in the landing day measurements relative to those observed before flight. These include decreased postural stability as evidenced by increased sway amplitudes and decreased equilibrium scores, with greater differences between pre- and post-flight during head tilt conditions. Five of ten astronauts have completed this study, and an ongoing normative study is obtaining repeated postural measures in healthy age, gender and height-matched control subjects using the same timeline scheduling as their astronaut counterparts.

Pre-flight scores to date for head erect, forward, backward, and moving at 0.33 Hz in the pitch plane were all in the upper range of the normative performance distributions. Consistent with our previous post-flight studies, performance on landing day was substantially decreased for conditions with absent visual and altered proprioceptive feedback. The most striking result on landing day; however, was on trials requiring active head movements at 0.33 Hz. All subjects fell on SOT-5 trials on landing day with active head movements (9 of 10 trials overall). The recovery curves for these crewmembers for trials with head erect followed similar trajectories to previous astronaut data recorded by our laboratory. The recovery profile for trials with the head movements, in contrast, had a similar recovery time constant but at significantly lower performance levels compared with the head erect trials. This decrease in performance during head tilts is consistent with our hypothesis that the physiological basis for disruption of balance control and spatial disorientation following g-transitions relates to a change in the reference frame used for central vestibular processing.

Pre- and Postflight Measures – Specific Aim 2: Our second specific aim is to examine the feasibility of altering the re-adaptation process following space flight by providing discordant canal-otolith-somatosensory stimuli using short-radius pitch axis centrifugation. The centrifuge profile utilized in this study represents a composite of different profiles that appeared to disrupt the recovery of one Spacelab astronaut as late as R+5 as described above. Although there were some interesting modulations of vertical and horizontal vergence eye movements during centrifugation, there were no apparent differences in these responses between pre- and post-flight. There were also no consistent differences between motion perception reports from pre- to post-flight. Although the postural performance following centrifugation was also not substantially changed in any of the five crewmembers tested to date in this study, this may reflect behavioral characteristics that contribute to the large inter-individual differences in neurovestibular symptoms. It is interesting to note that pre-flight scores of the five participants were all in the upper range of the normative performance distributions. The risk of centrifugation disrupting the re-adaptation process may be greater for individuals that score in the lower range of pre-flight performance distributions.