Information from this study will help in the design of sensorimotor adaptability training countermeasures that may be customized for each crewmember's individual characteristics. The study is almost completely retrospective, in that no new bed rest or flight studies are required.

To achieve these goals the following Aims will be pursued:

1) Aim 1: Determine whether baseline individual sensory biases and capabilities for strategic and plastic-adaptive responses predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration spaceflight. We will determine if participants' individual sensory biases in use of vision, vestibular, and proprioception as well as tests of strategic and long-term adaption predict the change from pre to post-tests after bed rest or spaceflight and determine if those biases predict rates of re-adaptation in sensorimotor performance.

2) Aim 2: Determine if baseline brain morphological and functional metrics predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration spaceflight. We will determine if individual differences in regional brain volumes (structural MRI), white matter integrity (diffusion tensor imaging, or DTI), functional network integrity (resting state functional connectivity MRI), and sensorimotor adaptation task-related functional brain activation (functional MRI) predict pre to post levels of decrements and their rates of re-adaptation in sensorimotor performance.

3) Aim 3: Determine if genetic markers predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration spaceflight. We will determine whether genetic polymorphisms in COMT, DRD2, BDNF, and genetic polymorphism of alpha2-adrenergic receptor are associated with pre to post levels of decrements in sensorimotor performance and rates of re-adaptation.

Developing predictive measures of sensorimotor adaptability will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and spaceflight studies. This data will be combined with predictor metrics -- behavioral, brain imaging, and genomic measures collected from these returning subjects to build models for predicting post-mission (bed rest or spaceflight) adaptive capability as manifested in their outcome measures. Comparisons of model performance for various groups of predictors will provide insight into how to design subject-specific countermeasures against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

This funding year multiple levels of approvals were obtained including Authority to Proceed from the Science Management Panel, Lifetime Surveillance of Astronaut Health (LSAH), and International Space Station Medical Projects (ISSMP) element in order to be able to recruit from all available crewmembers who had participated in prior studies to record their functional performance after spaceflight to participate in the study. A total of six crewmembers who had participated in prior spaceflight studies and three subjects who had participated in bed rest studies to quantify their functional performance before and after these missions agreed to participate in this study.

Preliminary results indicate a correlation between the subjects' pre mission ability to utilize somatosensory information from their feet and ankles to the change in performance abilities of dynamic balance performance as well as the change in recovery from fall functional test performance after spaceflight and bedrest. Another highlight was the findings from various studies across investigators' laboratories, using data from control subjects, that have shown individual sensory preferences, adaptation ability to surrogate sensorimotor environments, subjects' brain structure and functional connectivity as well subjects' single nucleotide polymorphisms in genetic markers can be used to predict subjects' ability to adapt to novel sensorimotor environments.

2. A control subject database was augmented to 45 subjects that have the same test of performance. Using information from these tests, data show that subjects' utilization of somatosensory information at the bottom of the feet and at the ankle joints were predictive of the ability to adapt to novel sensorimotor disturbance during walking. Further, the SNP in BDNF and DRD2 showed the ability to delineate subjects' ability to adapt to visuomotor disturbance during walking.

3. A control-subject group study (n=58) conducted at the University of Houston explored the link between adaptation in manual control and the classical split-belt treadmill locomotor adaptation task. Data showed a significant linear relationship between the number of attempts required to achieve adaptation in the two tasks. These data confirm the notion that a common central adaptive mechanism is employed across sensorimotor sub-systems.

4. A control subject study (n=34) at the University of Michigan investigated whether individual variability in the rate of visuomotor manual adaptation is associated with differences in regional gray matter volume and resting state functional connectivity. Resting state functional connectivity strength between sensorimotor, dorsal cingulate, and temporoparietal regions of the brain was found to predict the rate of learning during the early phase of the adaptation task. As for structural predictors, greater gray matter volume in temporoparietal and occipital regions predicted faster early learning, whereas greater gray matter volume in superior posterior regions of the cerebellum predicted faster late learning. These findings confirm that neural predictors of early and late adaptation may facilitate different aspects of sensorimotor adaptation that may be targeted by countermeasures.

5. A study conducted on people with benign paroxysmal positional vertigo (BPPV) explored the interaction between visual dependence and balance control. Control subjects with poor balance scores had significantly greater visual dependence, indicating reliance on visual cues can affect balance control. The side of impairment was strongly related to the side of perceived bias in the Earth vertical determined by BPPV subjects, indicating a relationship between the effect of BPPV with spatial orientation perception.

To achieve these goals the following Aims will be pursued:

1) Aim 1: Determine whether baseline individual sensory biases and capabilities for strategic and plastic-adaptive responses predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration spaceflight. We will determine if participants' individual sensory biases in use of vision, vestibular, and proprioception as well as tests of strategic and long-term adaptation predict the change from pre- to post-tests after bed rest or spaceflight and determine if those biases predict rates of re-adaptation in sensorimotor performance.

2) Aim 2: Determine if baseline brain morphological and functional metrics predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration spaceflight. We will determine if individual differences in regional brain volumes (structural MRI), white matter integrity (diffusion tensor imaging, or DTI), functional network integrity (resting state functional connectivity MRI), and sensorimotor adaptation task-related functional brain activation (functional MRI) predict pre to post levels of decrements and their rates of re-adaptation in sensorimotor performance.

3) Aim 3: Determine if genetic markers predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration spaceflight. We will determine whether genetic polymorphisms in COMT, DRD2, BDNF and genetic polymorphism of alpha2-adrenergic receptor are associated with pre to post levels of decrements in sensorimotor performance and rates of re-adaptation.

Developing predictive measures of sensorimotor adaptability will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and spaceflight studies. This data will be combined with predictor metrics -- behavioral, brain imaging, and genomic measures collected from these returning subjects to build models for predicting post-mission (bed rest or spaceflight) adaptive capability as manifested in their outcome measures. Comparisons of model performance for various groups of predictors will provide insight into how to design subject-specific countermeasures against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

1. NASA International Space Station Medical Project (ISSMP) element approved implementation of study for 51 subjects.

2. CFT 70 bed rest analog study Functional Task Test Control Group of subjects are being recruited by the NASA Test Subject Facility.

3. NASA Science Management Panel reviewed this study and have formulated a plan for implementation of the study: a) Use NSBRI funding until 31 May 2017. b) Proceed with easiest populations, presumably bed rest, retired astronauts, management astronaut, presumably in that order. c) Defer active astronauts until after data are acquired and approach is validated, then initiate HRP-funded study involving active astronauts, presumably after 31 May 2017.

4. One paper was published in the Frontiers of Systems Neuroscience by Dr. Rachael Seidler (Co-Investigator in this project) [Ed. note: See FY2015 report Bibliography] and a second paper is in review; two abstracts were published in proceedings of the Association for Research in Otolaryngology Annual Mid-Winter meeting and 5 other abstracts were presented at the Human Research Program Investigators' Workshop.

5. Retrospective Spaceflight and Bedrest data analysis -- lower limb joint strength and computerized dynamic posturography data that were collected as part of their medical requirement for subjects who participated in the CFT 70 bed rest and spaceflight campaigns to use with their corresponding data from functional tests were requested and obtained after approval from the NASA - AOHMG. Bed rest-induced calf strength losses account for 6-14% of concomitant changes in balance control, dynamic postural stability, and functional performance. Additional work to evaluate the influence of calf strength loss on the performance of longer and more plantarflexor-intensive tasks (e.g., ladder climb and uphill ambulation) is needed.

6. Dr. Bloomberg's project on developing predictors for sensorimotor adaptability program is being leveraged by increasing its scope beyond the original proposal.

Additional tests (Proprioceptive contribution to balance control; sensory organization tests 1-6; Vestibular threshold; Spatial orientation under otolith canal mismatch and four targeted single nucleotide polymorphisms using saliva samples) were performed on the same 16 subjects from whom data were collected. This contributed significantly towards a group of predictor test protocols for identifying adaptability to novel sensorimotor environments. This also meets one of the goals recommended by the NASA Sensorimotor Review Panels to reduce the number of tests to overcome redundancies and find efficiencies to streamline testing paradigms in post flight and post bed rest participants. The result of this endeavor was a reduced set of 14 tests were identified and reduced the time for testing session from around 6 hours of testing to a total of 3.45 hours including travel time to the MRI testing center (40 minutes of travel time).

The following publication is in process: Rahul Goel, Yiri De Dios, Nichole Gadd, Erin Caldwell, Brian Peters, Millard Reschke, Jacob Bloomberg, Lars Oddsson, Ajitkumar Mulavara. "Measuring the contributions of somatosensory information during unipedal postural control."

To achieve these goals the following Aims will be pursued:

1) Aim 1: Determine whether baseline individual sensory biases and capabilities for strategic and plastic-adaptive responses predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration space flight. We will determine if participants' individual sensory biases in use of vision, vestibular, and proprioception as well as tests of strategic and long-term adaption predict the change from pre to post-tests after bed rest or space flight and determine if those biases predict rates of re-adaptation in sensorimotor performance.

2) Aim 2: Determine if baseline brain morphological and functional metrics predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration space flight. We will determine if individual differences in regional brain volumes (structural MRI), white matter integrity (diffusion tensor imaging, or DTI), functional network integrity (resting state functional connectivity MRI), and sensorimotor adaptation task-related functional brain activation (functional MRI) predict pre to post levels of decrements and their rates of re-adaptation in sensorimotor performance.

3) Aim 3: Determine if genetic markers predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration space flight. We will determine whether genetic polymorphisms in COMT, DRD2, BDNF and genetic polymorphism of alpha2-adrenergic receptor are associated with pre to post levels of decrements in sensorimotor performance and rates of re-adaptation.

Developing predictive measures of sensorimotor adaptability will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. This data will be combined with predictor metrics -- behavioral, brain imaging, and genomic measures collected from these returning subjects to build models for predicting post-mission (bed rest or space flight) adaptive capability as manifested in their outcome measures. Comparisons of model performance for various groups of predictors will provide insight into how to design subject-specific countermeasures against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

1. NASA Institutional Review Board (IRB) approved study for 51 subjects.

2. NASA Test Readiness Review Board Approved study implementation.

3. Subject recruitment for this study - International Space Station Medical Project (ISSMP) and Flight Analog Project (FAP) have agreed to facilitate recruitment of returning astronauts and bed rest subjects who participated in the Functional Task Test Flight and CFT 70 bed rest analog studies.

4. Review of literature that has resulted in a review paper being submitted for possible publication in the Frontiers of Systems Neuroscience by Dr. Rachael Seidler (Co-Investigator in this project).

5. Identification of new tests that have shown potential predictors of adaptability and recruitment of two additional collaborators to participate in this study. Both of these identified collaborators are NSBRI First Awardees.

6. Leveraging data already collected from another project within the sensorimotor adaptability Team : Dr. Bloomberg's project on developing predictors for sensorimotor adaptability program is being leveraged to include data collected from 16 normative subjects as part of an effort to identify tests that contribute significantly towards identifying adaptability to novel sensorimotor environments. This also meets one of the goals laid down by the NASA Sensorimotor Review Panels to reduce the number of tests to overcome redundancies and find efficiencies to stream line testing paradigms in post flight and post bed rest participants.

To achieve these goals the following Aims will be pursued: 1) Aim 1: Determine whether baseline individual sensory biases and capabilities for strategic and plastic-adaptive responses predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration space flight. We will determine if participants’ individual sensory biases in use of vision, vestibular, and proprioception as well as tests of strategic and long-term adaption predict the change from pre-to post-tests after bed rest or space flight and determine if those biases predict rates of re-adaptation in sensorimotor performance.

2) Aim 2: Determine if baseline brain morphological and functional metrics predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration space flight. We will determine if individual differences in regional brain volumes (structural MRI), white matter integrity (diffusion tensor imaging, or DTI), functional network integrity (resting state functional connectivity MRI), and sensorimotor adaptation task-related functional brain activation (functional MRI) predict pre to post levels of decrements and their rates of re-adaptation in sensorimotor performance.

3) Aim 3: Determine if genetic markers predict both change and also the ability to re-adapt sensorimotor and functional performance after 70 days bed rest or short/long duration space flight. We will determine whether genetic polymorphisms in COMT, DRD2, BDNF, and genetic polymorphism of alpha2-adrenergic receptor are associated with pre to post levels of decrements in sensorimotor performance and rates of re-adaptation.

Developing predictive measures of sensorimotor adaptability will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember’s sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. This data will be combined with predictor metrics - behavioral, brain imaging, and genomic measures collected from these returning subjects to build models for predicting post-mission (bed rest or space flight) adaptive capability as manifested in their outcome measures. Comparisons of model performance for various groups of predictors will provide insight into how to design subject-specific countermeasures against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.