| Author and Affiliation: |
| Koppelmans, V. | (Michigan Univ., School of Kinesiology, Ann Arbor, MI, United States); |
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| Cassady, K. | (Michigan Univ., Dept. of Psychology, Ann Arbor, MI, United States); |
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| De Dios, Y. E. | (Wyle Science, Technology and Engineering Group, Houston, TX, United States); |
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| Szecsy, D. | (Bastion Technologies, Inc., Huntsville, AL, United States); |
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| Gadd, N. | (Wyle Science, Technology and Engineering Group, Houston, TX, United States); |
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| Wood, S. J. | (Azusa Pacific University, Dept. of Psychology, Azusa, CA, United States); |
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| Reuter-Lorenz, R. A. | (Universities Space Research Association, Houston, TX, United States); |
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| Kofman, I. | (Wyle Science, Technology and Engineering Group, Houston, TX, United States); |
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| Bloomberg, J. J. | (NASA Johnson Space Center, Houston, TX, United States); |
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| Mulavara, A. P. | (Michigan Univ., Dept. of Psychology, Ann Arbor, MI, United States); |
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| Ploutz-Snyder, L. | (Universities Space Research Association, Houston, TX, United States); |
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| Seidler, R. D. | (Michigan Univ., School of Kinesiology, Ann Arbor, MI, United States) |
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| Abstract: |
Long duration spaceflight microgravity results in cephalad fluid
shifts and deficits in posture control and locomotion. Effects of
microgravity on sensorimotor function have been investigated on Earth
using head down tilt bed rest (HDBR). HDBR serves as a spaceflight
analogue because it mimics microgravity in body unloading and bodily
fluid shifts. Preliminary results from our prior 70 days HDBR studies
showed that HDBR is associated with focal gray matter (GM) changes and
gait and balance deficits, as well as changes in brain functional
connectivity. In consideration of the health and performance of
crewmembers we investigated whether exercise reduces the effects of HDBR
on GM, functional connectivity, and motor performance. Numerous studies
have shown beneficial effects of exercise on brain health. We therefore
hypothesized that an exercise intervention during HDBR could
potentially mitigate the effects of HDBR on the central nervous system.
Eighteen subjects were assessed before (12 and 7 days), during (7, 30,
and ~70 days) and after (8 and 12 days) 70 days of 6-degrees HDBR at the
NASA HDBR facility in UTMB, Galveston, TX, US. Each subject was
randomly assigned to a control group or one of two exercise groups.
Exercise consisted of daily supine exercise which started 20 days before
the start of HDBR. The exercise subjects participated either in regular
aerobic and resistance exercise (e.g. squat, heel raise, leg press,
cycling and treadmill running), or aerobic and resistance exercise using
a flywheel apparatus (rowing). Aerobic and resistance exercise
intensity in both groups was similar, which is why we collapsed the two
exercise groups for the current experiment. During each time point
T1-weighted MRI scans and resting state functional connectivity scans
were obtained using a 3T Siemens scanner. Focal changes over time in GM
density were assessed using voxel based morphometry (VBM8) under SPM.
Changes in resting state functional connectivity was assessed using both
a region of interest (ROI, or seed-to-voxel) approach as well as a
whole brain intrinsic connectivity (i.e., voxel-to-voxel) analysis. For
the ROI analysis we selected 11 ROIs of brain regions that are involved
in sensorimotor function (i.e., L. Insular C., L. Putamen, R. Premotor
C., L.+R. Primary Motor C., R. Vestibular C., L. Posterior Cingulate G.,
R. Cerebellum Lobule V + VIIIb + Crus I, and the R. Superior Parietal
G.) and correlated their time course of brain activation during rest
with all other voxels in the brain. The whole brain connectivity
analysis tests changes in the strength of the global connectivity
pattern between each voxel and the rest of the brain. Functional
mobility was assessed using an obstacle course. Vestibular contribution
to balance was measured using Neurocom Sensory Organization Test 5.
Behavioral measures were assessed pre-HDBR, and 0, 8 and 12 days
post-HDBR. Linear mixed models were used to test for effects of time,
group, and group-by-time interactions. Family-wise error corrected VBM
revealed significantly larger increases in GM volume in the right
primary motor cortex in bed rest control subjects than in bed rest
exercise subjects. No other significant group by time interactions in
gray matter changes with bed rest were observed. Functional connectivity
MRI revealed that the increase in connectivity during bed rest of the
left putamen with the bilateral midsagittal precunes and the right
cingulate gyrus was larger in bed rest control subjects than in bed rest
exercise subjects. Furthermore, the increase in functional connectivity
with bed rest of the right premotor cortex with the right inferior
frontal gyrus and the right primary motor cortex with the bilateral
premotor cortex was smaller in bed rest control subjects than in bed
rest exercise subjects. Functional mobility performance was less
affected by HDBR in exercise subjects than in control subjects and post
HDBR exercise subjects recovered faster than control subjects. The group
performance differences and GM changes were not related. Exercise in
HDBR partially mitigates the adverse effect of HDBR on functional
mobility, particularly during the post-bed rest recovery phase. In
addition, exercise appears to result in differential brain structural
and functional changes in motor regions such as the primary motor
cortex, the premotor cortex and the putamen. Whether these central
nervous system changes are related to motor behavioral changes including
gait and balance warrants further research.
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