NOTE: End date changed to 09/30/2023 per PI (Ed., 7/7/21)

Deliverables: Statistical models will use combinations of behavioral metrics, brain structure metrics and genomic polymorphisms to understand individual decrements in post-flight functional task outcomes. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

Study Participants: This study will target recruitment of up to 30 astronauts who previously flew on ISS, including 6 obtained via the original Predictors study.

Risk Characterization, Quantification, Evidence: This project was directed toward the risk titled “Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks.” This study is addressing gaps SM-101 (risk characterization of postural control and locomotion) and SM-104 (evaluate weightlessness-induced changes in sensorimotor/vestibular function with changes in other brain functions). This study will help quantify inter-individual variability of sensorimotor decrements.

Countermeasure, Prototype Hardware or Software: The information derived from this study may be applied towards optimizing countermeasures based on preflight tests of sensorimotor biomarkers.

Post-flight Outcome Measures: Computerized dynamic posturography on R+0/1 was performed in 26 of 27 participants. Field testing (recovery from fall and tandem walk) was performed in 24 of 27 subjects, although not consistently at the same time points. For this preliminary analysis, we are using the time points that occur following return to Johnson Space Center (JSC) (referred to as R+0c), given these are available for most participants and more closely match when the posturography measures have been made. All of these measures continue to demonstrate high intersubject variability that is characteristic of postflight sensorimotor responses. The posture Sensory Organization Tests (SOT) use a continuous equilibrium score ranging between 0 – 100, with higher numbers representing better performance. These scores on R+0c ranged between 38 – 94 (median 83) for SOT-5 and 5 – 90 (median 57) on SOT-5M. A difference score (post-flight - pre-flight performance) was calculated, with more negative values representing greater deficits in performance relative to each individual’s preflight baseline. The range of SOT-5 (head erect) post-pre differences was 7 to -29 (median = -3.8), while the range of SOT-5M (head moving) was 6 to -83 (median = -19.4). Thus, the SOT-5M ratio scores are more variable given the timeframe of these measures (>R+24hrs) and may be more sensitive to vestibular contributions to standing balance. The recovery from fall (RFF) used time to stability in sec, with lower numbers representing better performance, resulting in a median of 8.6s (range 4.4 – 21.4 s) on R+0c. Difference scores were also calculated using preflight - postflight, so more negative values would also represent greater deficits in performance relative to each individual’s preflight baseline. The median in differences at R+0c was -3.0 (range 1.7 to -9.1). For reference, the median difference score for recovery from fall at the landing site (R+0a) was -9.4 (range -0.6 to -15.6). The tandem walk was performed with eyes open (TW-EO), and eyes closed (TW-EC), and scored as percent of correct steps ranging from 0 to 100. Note that for eyes open, only one subject scored less than a perfect 100 on this task preflight. TW-EC was more challenging, with a preflight median of 88.8 % (range 50 – 100%). Since higher numbers represent better performance, these difference scores were calculated using post-flight - pre-flight performance so more negative values would continue to represent greater deficits in performance across all outcome measures. For eyes closed, the median in differences in correct steps at R+0c was -44.8 (range -11.1 to -97.0). For reference the median difference score for tandem walk eyes closed at R+0a was -77.2 (range -34.8 to -97.0). For eyes open, the median in differences at R+0c was -10.0 (range 0 to -100.0). For reference the median difference score for tandem walk eyes open at R+0a was -59.6 (range -12.5 to -100.0). Not surprising, tasks with eyes open tend to exhibit fewer decrements by R+0c since visual compensation is one means of dealing with the postflight vestibular disruption. The relatively poor correlation between these postflight measures may reflect differences in how crewmembers utilize visual compensation. For example, the difference scores for eyes closed SOT-5 and eyes open RFF were negatively correlated (rho = -0.48, p = 0.02) and differences scores between TW-EC and TW-EO were poorly correlated 0.28 (p = 0.21).

Subjective ratings of both inflight and postflight adaptation continue to be captured using a Qualtrics survey to supplement the objective ratings. For both early inflight and postflight periods, crewmembers were asked to rate how severely adaptation impacted their ability to perform functional tasks, from 0 being no impact to 4, representing severe impacts, including not attempting tasks and/or deliberate restriction of motion. Based on the limited sample of responses received to date (n = 17 of 27), 70% of crewmembers rated postflight impacts to task performance (median = 2, range 0 - 4) higher than inflight impacts (median = 1, range 0 - 3). A different question asked how long they restricted movements, from 0 = no impact or restriction of movements to 4 representing more than 3 days. Fourty-seven percent of crewmembers indicated they needed to restrict movements over a longer period postflight (median = 2, range 0 - 4) than inflight (median = 2, range 0 – 3) while only crewmembers reported restricting movements longer inflight. The survey also included open questions to capture what recommendations they had for enhancing adaptation based on their own experience, e.g., closing eyes during parachute opening, initially restricting then incrementally increasing movements, prophylactic medication, and allowing for sleep.

Sensory Dependency Measures: Sensitivity to visual motion was measured during treadmill walking while viewing a moving (virtual hallway) visual scene. The dependent variable was lateral torso translation during scene oscillation (amplitude at 0.3 Hz scene motion). Vestibular sensitivity involves a perceptual direction-recognition task while seated with eyes closed during lateral translations. The dependent variables (threshold and bias) were derived from psychometric curve fit. The ability to balance using proprioception is assessed by monitoring medial-lateral center of pressure (COP) during a one-legged stance on a horizontal air-bearing surface (eyes open and eyes closed). Measures include both range and root mean square (RMS) COP of medial-lateral and anterior-posterior directions from the force plate. Based on the current data set, there do not appear to be any significant correlations of these single dependency measures with the postflight outcome measures. Future statistical analysis will explore combining these dependency measures with others to increase predictive power. For example, visual dependency during treadmill walking is significantly correlated with the adaptive Functional Mobility Test (aFMT) scores (rho = 0.4, p = 0.039), and therefore a combination of both measures may be a more robust measure of visual dependency.

Sensory Adaptability Measures: The Adaptive Functional Mobility Test (AFMT) measured the time to complete navigating an obstacle course while wearing up/down reversing prisms over 5 trials. While the performance continued to improve on average throughout the 5 trials, the variability in performance was greatest during the first trial (range 65 – 422 sec to complete the course). There was a clear adaptive change across trials and the time constant from a single exponential fit using all subjects was 1.4 trials. To capture adaptability over the 5 trials, we calculated a cumulative time-to-complete (cTTC) score. For two subjects with similar trial 1 TTC measures, a lower cumulative TTC will reflect the improved performance on later trials and is therefore interpreted as having greater adaptability. The trial 1 TTC and the cumulative TTC are highly correlated (rho 0.9, p<0.001), although we plan to use the cumulative TTC as our primary adaptability measure. Interestingly, based on the data collected to date, the cTTC is most negatively correlated with eyes closed conditions, e.g., posturography SOT-5 (rho = -0.41, p = 0.038) and the tandem walk (rho = -0.53, p = 0.009). Adaptability is also being assessed with the Treadmill Sensory Discordance Test. Changes in both stride frequency and reaction time to an auditory cue while walking with a virtual linear hallway on an oscillating treadmill are recorded after 1 and 4 minutes of walking on the oscillating treadmill. These scores are normalized with respect to the baseline walking period, with scores of 1 being equal to baseline performance and scores greater than 1 representing longer reaction time and higher stride frequency. On average, subjects tend to take 25% longer on the reaction time and walk with a 10% higher stride frequency during the initial minute of exposure to the sensory discordance. While both reaction time and stride frequency trend lower towards baseline over the 5 minute exposure, one would not necessarily expect a similar stride frequency as adopted without the surface perturbation. Therefore, increases in stride frequency relative to baseline are not necessarily maladaptive during the treadmill oscillation, and it is challenging to derive an “adaptability” metric from this data set.

Neuroimaging measures: Further neuroimaging analysis has been on hold pending the completion of all data collection. The preflight neuroimages to be used for this analysis have been obtained and will be processed in the coming year.

Genetic measures: Variations in four genes have been analyzed from saliva samples, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF), and the a2-adrenergic receptor. The distribution of the different alleles were within expected range. There does not appear to a clear pattern of alleles in any of the four genes that predict post-flight performance.

Summary of Preliminary Findings: There is considerable variability among the post-flight performance outcomes for the 27 participants to date. Based on a partial sample using an ordinal scale survey, 70% indicated their ability to perform functional tasks was more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures, e.g., the cumulative time to complete during the aFMT is negatively correlated with the pre-to-post-flight changes in tandem walking with eyes closed. Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

Deliverables: Statistical models will use combinations of behavioral metrics, brain structure metrics and genomic polymorphisms to understand individual decrements in post-flight functional task outcomes. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

Study Participants: This study will target recruitment of up to 30 astronauts who previously flew on ISS, including 6 obtained via the original Predictors study.

Risk Characterization, Quantification, Evidence: This project was directed toward the risk titled “Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks.” This study is addressing gaps SM-101 (risk characterization of postural control and locomotion) and SM-104 (evaluate weightlessness-induced changes in sensorimotor/vestibular function with changes in other brain functions). This study will help quantify inter-individual variability of sensorimotor decrements.

Countermeasure, Prototype Hardware or Software: The information derived from this study may be applied towards optimizing countermeasures based on preflight tests of sensorimotor biomarkers.

Post-flight Outcome Measures: Computerized dynamic posturography was performed in 20 of 21 participants. Field testing (recovery from fall and tandem walk) was performed in 20 of 21 subjects, although not consistently at the same time points. For this preliminary analysis, we are using the time points that occur following return to Johnson Space Center (JSC), given these are available for all participants and more closely match when the posturography measures have been made. All of these measures continue to demonstrate high intersubject variability that is characteristic of postflight sensorimotor responses. The posture Sensory Organization Tests (SOT) use a continuous equilibrium score ranging between 0-100, with higher numbers representing better performance. A difference score (post-flight - pre-flight performance) was calculated, with more negative values representing greater deficits in performance relative to each individual’s preflight baseline. The range of SOT-5 (head erect) post-pre differences was 7 to -29 (median = -3.8), while the range of SOT-5M (head moving) was 6 to -83 (median = -19.4). Thus, the SOT-5M ratio scores are more sensitive given the timeframe of these measures (>R+24hrs) and are preferred to understand the variability in performance during vestibular contributions to standing balance. The recovery from fall (RFF) used time to stability in sec, with lower numbers representing better performance. Therefore, difference scores were calculated using preflight - postflight, so more negative values would also represent greater deficits in performance relative to each individual’s preflight baseline. The range in differences at R+0c was 1.7 to -9.1 (median = -3.0). For reference, the median difference score for recovery from fall at R+0a was -9.4 (range -0.6 to -15.6). The tandem walk was performed with eyes open (TW-EO), and eyes closed (TW-EC) and scored as a percent of correct steps ranging from 0 to 100. Note that for eyes open, all crewmembers scored a perfect 100 on this task preflight. Since higher numbers represent better performance, these difference scores were calculated using post-flight - pre-flight performance, so more negative values would continue to represent greater deficits in performance across all outcome measures. For eyes closed, the range in differences at R+0c was -11.1 to -97.0 (median = -44.8). For reference, the median difference score for tandem walk eyes closed at R+0a was -77.2 (range -34.8 to -97.0). For eyes open, the range in differences at R+0c was 0 to -100.0 (median = -10). For reference, the median difference score for tandem walk eyes open at R+0a was -59.6 (range -12.5 to -100.0). Not surprisingly, tasks with eyes open tend to exhibit fewer decrements by R+0c since visual compensation is one means of dealing with the postflight vestibular disruption. The relatively poor correlation between these postflight measures may reflect differences in how crewmembers utilize visual compensation. For example, the Spearman’s rho correlation between difference scores for SOT-5M and RFF was 0.105 (p = 0.67) and between TW-EC and TW-EO was 0.384 (p = 0.10).

This past year we added a Qualtrics survey to capture subjective ratings of both inflight and postflight adaptation to supplement the objective ratings. For both early inflight and postflight periods, crewmembers were asked to rate how severely adaptation impacted their ability to perform functional tasks, from 0 being no impact to 4, representing severe impacts, including not attempting tasks and/or deliberate restriction of motion. Based on the limited sample of responses received to date (n = 10 of 21), crewmembers tended to rate postflight adaptation impacting their task performance (median = 3, range 2 - 4) more than inflight (median = 2, range 0 - 3). A different question asked how long they restricted movements, from 0 = no impact or restriction of movements to 4 representing more than 3 days. Again, crewmembers indicated they needed to restrict movements over a longer period postflight (median = 3, range 0 - 4) than inflight (median = 2, range 0 – 3). The survey also included open questions to capture what recommendations they had for enhancing adaptation based on their own experience, e.g., closing eyes during parachute opening, initially restricting then incrementally increasing movements, prophylactic medication, and allowing for sleep.

Sensory Dependency Measures: Sensitivity to visual motion was measured during treadmill walking while viewing a moving (virtual hallway) visual scene. The dependent variable was lateral torso translation during scene oscillation (amplitude at 0.3 Hz scene motion). Higher visual dependency appears related to lower recovery on tandem walk eyes closed (rho = -0.45, p = 0.04, n = 20). Vestibular sensitivity involves a perceptual direction-recognition task while seated with eyes closed during lateral translations. The dependent variables (threshold and bias) were derived from psychometric curve fit. Preliminary analysis suggests higher vestibular sensitivity was marginally correlated with higher recovery on SOT-5M (rho = -0.5, p=0.07). The ability to balance using proprioception is assessed by monitoring medial-lateral COP during a one-legged stance on a horizontal air-bearing surface (eyes open & eyes closed). Measures include both range and root mean square (RMS) center of pressure (COP), although medial-lateral and anterior-posterior directions from the force plate.

Sensory Adaptability Measures: The Adaptive Functional Mobility Test (AFMT) measured the time to complete navigating an obstacle course while wearing up/down reversing prisms (5 trials). While the performance continued to improve on average throughout the 5 trials, the variability in performance was greatest during the first trial (range 65 – 422 sec to complete the course). Slower AFMT times were significantly correlated with lower recovery on tandem walk eyes closed (rho = -0.5, p=0.025, n=20). Not surprisingly, the AFMT trial 1 times are highly correlated with our visual dependency measure described above (rho = 0.56, p = 0.008, n=21). Adaptability is also being assessed with the Treadmill Sensory Discordance Test. Changes in both stride frequency and reaction time to an auditory cue while walking with a virtual linear hallway on an oscillating treadmill are recorded after 1 and 4 minutes of walking on the oscillating treadmill.

Neuroimaging measures: This past year, we published a manuscript describing preliminary findings assessing the relationships of metrics derived from MRI scans collected from astronauts with motor performance post-flight. Structural and diffusion MRI scans from 14 astronauts were collected before launch and motor measures (balance performance, speed of recovery from fall, and tandem walk step accuracy) collected pre-flight and post-flight were analyzed. Regional measures of gray matter volume (motor cortex, paracentral lobule, and cerebellum), myelin density (motor cortex, paracentral lobule, and corticospinal tract), and white matter microstructure (corticospinal tract) were derived as a-priori predictors. Additional whole-brain analyses of cortical thickness, cerebellar gray matter and cortical myelin were also tested for associations with post-flight and pre-to-post-flight motor performance. The pre-selected regional measures were not significantly associated with motor behavior. However, whole-brain analyses showed that paracentral and precentral gyri thickness significantly predicted recovery from fall post-spaceflight. The thickness of vestibular and sensorimotor regions, including the posterior insula and the superior temporal gyrus, predicted balance performance post-flight and pre-to-post-flight decrements. Greater cortical thickness pre-flight predicted better performance post-flight. Regional thickness of somatosensory, motor, and vestibular brain regions has some predictive value for post-flight motor performance in astronauts, which may be used for the identification of training and countermeasure strategies targeted for maintaining operational task performance.

Genetic measures: Variations in four genes have been analyzed from saliva samples, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF), and the a2-adrenergic receptor. The distribution of the different alleles was within the expected range. There does not appear to be a clear pattern of alleles in any of the four genes that predict post-flight performance. Genetic analysis of the 6 new subjects is on hold for batch processing.

Summary of Preliminary Findings: There is considerable variability among the post-flight performance outcomes for the 21 participants to date. Based on a partial sample using an ordinal scale survey, 80% indicated their ability to perform functional tasks was more impacted postflight relative to inflight with, 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. Based on our preliminary findings, there are apparent relationships between individual measures and specific post-flight outcome measures. We anticipate that combining biomarkers will increase predictive power, and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery, including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

Deliverables: Statistical models will use combinations of behavioral metrics, brain structure metrics, and genomic polymorphisms to understand individual decrements in post-flight functional task outcomes. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

Study Participants: This study will target recruitment of up to 30 astronauts who previously flew on the International Space Station (ISS), including 6 obtained via the original Predictors study.

Risk Characterization, Quantification, Evidence: This project was directed toward the Sensorimotor gap SM24 [Integrated Research Plan (IRP) Rev F): Determine if the individual capacity to produce adaptive change (rate and extent) in sensorimotor function to transitions in gravitational environments can be predicted with preflight tests of sensorimotor adaptability.] [Ed. note October 2021: Gaps have since change; see Human Research Roadmap https://humanresearchroadmap.nasa.gov/ ]

Countermeasure, Prototype Hardware, or Software: The information derived from this study may be applied towards optimizing countermeasures based on preflight tests of sensorimotor biomarkers.

(1) To supplement our quantitative post-flight outcome measures, a new survey was added to capture participant’s subjective self-rating of how severely their adaptation impacted their ability to perform functional tasks and how long it took to adapt (recover) so that they were no longer restricting movement (both early inflight and postflight). This survey will be completed retrospectively for previous participants using a Qualtrics link and will be obtained prospectively for future participants.

(2) Dr. Koppelmans (University of Utah) has performed additional neuro-imaging processing using a new myelin mapping pipeline to augment the prior Diffusion Tensor Imaging analyses. It was determined that a software upgrade at the Victory Lakes imaging facility during the middle of the testing timeframe required a correction step that may limit the utility of this pipeline.

(3) The six degree-of-freedom platform that is used for some of the sensory dependency and adaptability tests has been upgraded (MOOG model 130 to model 170). This changeout allowed upgrades to the software (unsupported DOS to Windows based), increased payload rating, and improved the emergency stop functionality. The LabView code for stimulus control and data acquisition was also upgraded. Participant recruitment was recently resumed for the study and Qualtrics survey data collection on the existing 15 participants is ongoing.

Preliminary results (presented at the February Investigator Workshop-IWS): The 15 participants to date include 13M/2F and 9 veterans/6 first time flyers. The behavioral and genetic measures have been obtained an average of 3.4 years following the last mission (range 0.5 – 14.1 yr).

Post-flight Outcome Measures: Posturography data is available for all 15 participants. Field testing (recovery from fall and tandem walk) are available for 14 of 15 subjects. Of the two posture conditions (Sensory Organization Test (SOT) 5 and 5M)), trials requiring head movements with eyes closed on a sway-referenced (unstable) surface resulted in more variable responses. A ratio score (post-flight performance / pre-flight performance) was calculated, with a ratio of 1.0 being representing recovery to preflight baseline levels. The range of SOT-5 (head erect) ratios was 0.57-1.09 while the range of SOT-5M (head moving) was 0.08-1.07. Thus, the SOT-5M ratio scores are preferred to understand the variability in performance given the timeframe of these measures (>R+24hrs). Ratios for both recovery from fall and tandem walk were highly correlated across the three landing day test sessions (R0a medical tent/airport, R0b refueling stop, R0c JSC-Johnson Space Center). Since there were additional missing data from the R+0a and R0b sessions, the R0c session data was used for this preliminary analysis. The range of ratios for the recovery from fall was 0.32-1.24 and for tandem walk was 0.00-0.61. Given the differences in recovery time constants, and differences in what sensorimotor functions they are designed to reflect (e.g., eyes open versus eyes closed), it is not surprising that the ratio scores for this limited sample set were not correlated.

Sensory Dependency Measures: Sensitivity to visual motion was measured during treadmill walking while viewing a moving (virtual hallway) visual scene. The dependent variable was lateral torso translation during scene oscillation (amplitude at 0.3 Hz scene motion). Higher visual dependency appears related with lower recovery on tandem walk eyes closed (rho = -0.47). Vestibular sensitivity involves a perceptual direction-recognition task while seated with eyes closed during lateral translations. The dependent variables (threshold and bias) were derived from psychometric curve fit. Although data was only available for 9 subjects for this task, preliminary analysis suggests higher vestibular sensitivity was correlated with higher recovery on SOT-5M (rho = -0.71, p=0.03). The ability to balance using proprioception is assessed by monitoring medial-lateral center of pressure (COP) during one-legged stance on a horizontal air-bearing surface (eyes open & eyes closed). Measures include both range and root mean square (RMS) center of pressure (COP) although medial-lateral and anterior-posterior directions from the force plate. The resultant COP Range varied between 20 – 150 mm with eyes closed.

Sensory Adaptability Measures: The Adaptive Functional Mobility Test (AFMT) measured the time to complete navigating an obstacle course while wearing up/down reversing prisms (10 trials). While the performance continued to improve on average throughout the 10 trials, the variability in performance was greatest during the first trial (range 65 – 422 sec to complete the course). Slower AFMT times were significantly correlated with lower recovery on tandem walk eyes closed (n=14, rho = -0.62, p=0.02). Adaptability is also being assessed with the Treadmill Sensory Discordance Test. Changes in both stride frequency and reaction time to an auditory cue while walking with a virtual linear hallway on an oscillating treadmill are recorded after 1 and 4 min of walking on the oscillating treadmill.

Neuroimaging measures: Individual differences in regional brain volumes (using Structural MRI) and white matter microstructure (using Diffusion Tensor Imaging) are analyzed as potential predictors of adaptive capacity. Based on our preliminary analysis, differences in cerebellar volume Lobule VI (involved in sensorimotor adaptation) appears positively correlated with higher post-flight scores on SOT-5M (p=.044, eta2=.35) and higher recovery ratios on RFF prone-to-stand test (left: p=<.001, eta2=.75).

Genetic measures: Variations in four genes have been analyzed from saliva samples, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF), and the a2-adrenergic receptor. The distribution of the different alleles were within expected range. There does not appear to a clear pattern of alleles in any of the four genes that predict post-flight performance.

Summary of Preliminary Findings: There is considerable variability among the post-flight performance outcomes for the 15 participants to date. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures; however, additional data is needed to draw conclusions. Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses.

Deliverables: Statistical models will use combinations of behavioral metrics, brain structure metrics, and genomic polymorphisms to understand individual decrements in post-flight functional task outcomes. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

Study Participants: This study will target recruitment of up to 30 astronauts who previously flew on the International Space Station (ISS), including 6 obtained via the original Predictors study.

Risk Characterization, Quantification, Evidence: This project was directed toward the Sensorimotor gap SM24 [Integrated Research Plan (IRP) Rev F): Determine if the individual capacity to produce adaptive change (rate and extent) in sensorimotor function to transitions in gravitational environments can be predicted with preflight tests of sensorimotor adaptability. ]

Countermeasure, Prototype Hardware, or Software: The information derived from this study may be applied towards optimizing countermeasures based on preflight tests of sensorimotor biomarkers.

Key Personnel Changes: Scott Wood is the new Principal Investigator for the study, and Jacob Bloomberg is now a Co-Investigator following his affiliation with the NASA Emeritus program.

Post-flight Outcome Measures: Posturography data is available for all 15 participants. Field testing (recovery from fall and tandem walk) are available for 14 of 15 subjects. Of the two posture conditions (Sensory Organization Test 5 and 5M), trials requiring head movements with eyes closed on a sway-referenced (unstable) surface resulted in more variable responses. A ratio score (post-flight performance / pre-flight performance) was calculated, with a ratio of 1.0 being representing recovery to preflight baseline levels. The range of SOT-5 (head erect) ratios was 0.57-1.09 while the range of SOT-5M (head moving) was 0.08-1.07. Thus, the SOT-5M ratio scores are preferred to understand the variability in performance given the timeframe of these measures (>R+24hrs). Ratios for both recovery from fall and tandem walk were highly correlated across the three landing day test sessions (R0a medical tent/airport, R0b refueling stop, R0c JSC). Since there were additional missing data from the R+0a and R0b sessions, the R0c session data was used for this preliminary analysis. The range of ratios for the recovery from fall was 0.32-1.24 and for tandem walk was 0.00-0.61. Given the differences in recovery time constants, and differences in what sensorimotor functions they are designed to reflect (e.g., eyes open versus eyes closed), it is not surprising that the ratio scores for this limited sample set were not correlated.

Sensory Dependency Measures: Sensitivity to visual motion was measured during treadmill walking while viewing a moving virtual visual scene. The dependent variable was lateral torso translation during scene oscillation (amplitude at 0.3 Hz scene motion). Higher visual dependency appears related with lower recovery on tandem walk eyes closed (rho = -0.47). Vestibular sensitivity involves a perceptual direction-recognition task while seated with eyes closed during lateral translations. The dependent variables (threshold and bias) were derived from psychometric curve fit. Although data was only available for 9 subjects for this task, preliminary analysis suggests higher vestibular sensitivity was correlated with higher recovery on SOT-5M (rho = -0.71, p=0.03). The ability to balance using proprioception is assessed by monitoring medial-lateral COP during one-legged stance on a horizontal air-bearing surface (eyes open & eyes closed). Measures include both range and root mean square (RMS) center of pressure (COP) although medial-lateral and anterior-posterior directions from the force plate. The resultant COP Range varied between 20 – 150 mm with eyes closed.

Sensory Adaptability Measures: The Adaptive Functional Mobility Test (AFMT) measured the time to complete navigating an obstacle course while wearing up/down reversing prisms (10 trials). While the performance continued to improve on average throughout the 10 trials, the variability in performance was greatest during the first trial (range 65 – 422 sec to complete the course). Slower AFMT times were significantly correlated with lower recovery on tandem walk eyes closed (n=14, rho = -0.62, p=0.02). Adaptability is also being assessed with the Treadmill Sensory Discordance Test. Changes in both stride frequency and reaction time to an auditory cue while walking with a virtual linear hallway on an oscillating treadmill are recorded after 1 and 4 min of walking on the oscillating treadmill.

Neuroimaging measures: Individual differences in regional brain volumes (using Structural MRI) and white matter microstructure (using Diffusion Tensor Imaging) are analyzed as potential predictors of adaptive capacity. Based on our preliminary analysis, differences in cerebellar volume Lobule VI (involved in sensorimotor adaptation) appear positively correlated with higher post-flight scores on SOT-5M (p=.044, eta2=.35) and higher recovery ratios on RFF prone-to-stand test (left: p=<.001, eta2=.75).

Genetic measures: Variations in four genes are being analyzed from saliva samples, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF), and the a2-adrenergic receptor.

Microgravity exposure results in an adaptive central reinterpretation of information from multiple sensory sources to produce a sensorimotor state appropriate for motor actions in this unique environment, but this new adaptive state is no longer appropriate for the 1G gravitational environment on Earth. These alterations may disrupt the ability to perform mission critical functional tasks requiring ambulation, manual control, and gaze stability. Astronauts who return from spaceflight show significant inter-subject variations in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which each individual astronaut will be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to determine, before actual spaceflight, which crewmembers will experience the largest challenges in adaptive capacity. Obtaining this information will allow us to design and implement better sensorimotor adaptability training countermeasures that will be customized for each crewmember’s unique adaptive capabilities.

The goal of this project is to characterize a set of predictive measures that include:

1. behavioral tests to assess sensory bias and adaptability; 2. imaging to determine individual brain morphological and functional features; 3. genotype markers for genetic polymorphisms that play a role in the neural pathways underlying sensorimotor adaptation.

Deliverables: This study will target recruitment of up to n=30 with no less than 15 subjects for this study including completing data collection for n=15 subjects and analysis (x 1 test session). Risk Characterization, quantification, and evidence will be provided in final report and publication. This project will produce a set of predictive measures to determine individual capability for rapid sensorimotor adaptation allowing the determination of volume and type of sensorimotor adaptability training countermeasures targeted for individual sensory integration profiles. This will also additionally inform the program on the ability to predict individual sensorimotor risk profile associated with spaceflight.

NOTE April 2020: Continuation of "Sensorimotor Predictors of Postlanding Functional Task Performance (PI=Bloomberg)," with new Principal Investigator Dr. Scott Wood, due to previous PI Dr. Jacob Bloomberg's retirement. Dr. Ajitkumar P. Mulavara was original PI of this project]