Our Aims were to:

Aim 1- Identify changes in brain structure, function, and network integrity as a function of 60 days head down tilt bed rest and characterize their time course: We acquired brain structural and functional images at two time points pre-, two time points during, and three time points post- bed rest in 18 individuals and 16 controls who were tested at four time points but otherwise went around their daily lives. We hypothesized that bed rest participants would exhibit changes from pre- to post- the intervention that were significantly greater than those seen in control participants across the same time period. Scans conducted during and following bed rest characterized the time course of changes and recovery.

Aim 2- Specify relationships between structural and functional brain changes and performance and characterize their time course: We administered a broad ranging battery of sensory, motor, and cognitive assessments at the time points described for Aim 1. We hypothesized that bed rest participants would exhibit pre- to post-intervention decrements in sensorimotor performance as we have shown in our past work, which we expected would correlate with the neural changes identified under Aim 1. Additionally, for some measures and time points, we expected that there might be no performance effects despite alterations in brain structure and function due to compensatory brain processes, which would be identifiable with neuroimaging approaches. The measures we acquired can be categorized into behavioral assessments and brain imaging assessments. The behavioral tests measured outside of the scanner included: card and cube rotation tests of spatial working memory, digit symbol substitution test of processing speed, rod and frame test of visual bias, pegboard test of bimanual coordination, sensory organization test of vestibular-mediated balance, functional mobility test of obstacle course navigation and vestibular evoked myogenic potential to assess vestibular function.

The neuroimaging tests of brain structure and function included: structural MRI to measure regional brain volumes and relative gray matter density, diffusion weighted scans (often referred to as DTI) to measure structural connectivity integrity, resting state functional MRI to measure functional connectivity integrity, and functional MRI to measure brain networks engaged during the performance of various tasks. The latter tasks included: imaging of the functional vestibular cortex, brain regions engaged during single and dual tasking of cognitive and motor behaviors, brain regions engaged during adaptation of pointing movements to perturbed visual feedback, and brain regions engaged for spatial working memory and foot tapping.

We have nearly completed data analyses and manuscript preparation. We have one paper published, one under second review, and several more that are nearly ready to submit. We found robust changes with bed rest in balance and functional mobility, replicating other studies that have previously reported sensorimotor declines. We also observed changes in brain gray matter volume, functional connectivity, and task based activation that were specific to the time period of the bed rest intervention, many of which were associated with the magnitude of behavioral change. Some metrics exhibited complete recovery by our last time point 12 days post bed rest, while others were trending towards recovery but had not yet returned to baseline levels.

Publication in revision: Kopplemans V, Bloomberg JJ, De Dios YE, Wood SJ, Reuter-Lorenz PA, Kofman IS, Riascos R, Mulavara AP, & Seidler R., "Brain plasticity and sensorimotor deterioration as a function of 70 days head down tilt bed rest." [Ed. note August 2017--now published August 2017 in PLoS One; see Bibliography section]

We have made significant progress during our second year of support. We continued data collection for our bed rest study and initiated the data collection of 8 normative control subjects, six of whom have completed all four time points. It should be noted that this normative control group will be used for comparison for both our NSBRI funded bed rest study and our NASA funded flight study. During Year 3 we will finish data collection for both the bed rest subjects and normative control subjects and continue analyses of our behavioral and MRI data, with a particular emphasis on addressing whether or how the two types of metrics change together as a function of bed rest. In addition, we will combine the results of the bed rest subjects and the normative control subjects in order to place the results of the bed rest subjects into perspective in terms of effects of bed rest versus potential task learning effects and stability of our protocol.

We have made great progress during our second year of support. We initiated the data collection for normative control subjects and have obtained complete data for 6 subjects so far. Also, we added an extra structural MRI measure (i.e., T2-weighted image) to the MRI protocols of our normative and bed rest subjects. T2-weighted imaging is better able in visualizing fluid, and thus could be a more sensitive method to detect fluid redistribution as a result of spaceflight/bed rest that could induce increased intracranial pressure. Our analyses of brain structure have revealed focal and global changes in frontal, temporal, and parietal regions of the brain. Furthermore, we observed increases in third ventricle volume with accumulating time in bed rest.

We have made great progress during our first year of support. Our stand alone protocol received IRB approval from the University of Michigan and NASA and was then wrapped into the bed rest Flight Analog Project UTMB IRB protocol. We invested an extensive amount of time and effort into assembling, integrating, and troubleshooting our hardware and software with the bed rest facility resources. This included developing and setting up unique hardware and software to enable functional MRI testing at UTMB Galveston, which previously had only acquired structural and clinical MRI scans. We also ran numerous pilot tests to ensure that we could collect our data within the time allotted and to verify that we were getting clean and reliable metrics. We have made one methodological change as a result of our pilot testing. We initially were stimulating the functional vestibular cortex via auditory clicks of a particular sound decibel. This moves fluid in the inner ear, stimulating vestibular receptor hair cells. The clicks, although within the OSHA safety standards, are quite loud and difficult for some subjects to tolerate. Moreover, the brain activity associated with this mode of stimulation was rather variable across test sessions for the initial subjects. As a result, we have extensively piloted and are now implementing vestibular stimulation with a head tapper device. This pneumatically driven device taps the head at a very low force level. The resulting vibration is transmitted via bone conduction to the vestibular system. Thus far, the brain activation patterns associated with this mode of stimulation appear to have better reliability. Over the next year we will acquire data from additional subjects and continue analyses of our behavioral and MRI data, with a particular emphasis on addressing whether / how the two types of metrics change together as a function of bed rest. Moreover, we will soon be launching our longitudinal control study.

We have made great progress during our first year of support. Our stand alone protocol received IRB approval from the University of Michigan and NASA and was then wrapped into the bed rest Flight Analog Project UTMB IRB protocol. We invested an extensive amount of time and effort into assembling, integrating, and troubleshooting our hardware and software with the bed rest facility resources. This included developing and setting up unique hardware and software to enable functional MRI testing at UTMB Galveston, which previously had only acquired structural and clinical MRI scans. We also ran numerous pilot tests to ensure that we could collect our data within the time allotted and to verify that we were getting clean and reliable metrics. We have streamlined our analytical approaches to include assessments of test retest reliability across the first two pre test time points as well as repeated measures approaches for evaluating the impact of bed rest. Thus far we have observed high intraclass correlations for our pre test metrics across five participants tested, and robust changes in behavioral and brain functional metrics with bed rest (n = 3 completed). Our analyses of brain structure have not yielded any effects of bed rest; however, data from only two participants have been analyzed thus far, and we also had some challenges with acquiring MRI data using consistent parameters. This issue has been resolved for testing moving forward.