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Exercise Effects on Central Nervous System Function and Structure in Bed Rest (First Award Fellowship)

Principal Investigator:
Vincent Koppelmans, Ph.D.

University of Michigan

Spaceflight results in impairments in gait, balance, and cognition. Preventing these dysfunctions is important in terms of crew health and success of space missions. These adverse effects of spaceflight likely have a central nervous system component considering that experimental studies showed microgravity-induced alterations of neural tissue in motor brain regions. Long-duration bed rest has proven to be a good model to study the effects of microgravity on motor performance. Two 70-days bed rest studies with pre, during, and post assessments of which data collection was recently completed focus on: 1) cognition, sensorimotor performance, and the brain using behavioral tests and MRI; and 2) how exercise might counteract microgravity-induced changes in physical fitness, by comparing exercise and control subjects on fitness outcome measures. These studies were being conducted simultaneously using the same subjects. Preliminary results show that bed rest affects motor function and brain structure. Multiple terrestrial studies have shown that aerobic exercise has a positive effect on cognition and brain structure. The current project aims to combine data of the two above-described bed rest studies to formally investigate exercise as a preventive countermeasure for microgravity-induced cognitive, sensorimotor, brain functional and structural changes.

NASA Taskbook Entry

Technical Summary

Altered gravity from Earth to low Earth orbit is one of the main factors that affect sensorimotor function in astronauts and cosmonauts. Mechanisms underlying microgravity-related sensorimotor dysfunction include reorganization of information from graviceptors and their interaction with the semicircular canals, bone density loss, and muscle unloading. In addition, experimental studies have shown that exposure to microgravity can result in structural changes in motor brain regions. Furthermore, a recent retrospective longitudinal study reported detrimental effects of spaceflight on the eye, optic nerve, and pituitary gland that were hypothesized to be resulting from cephalad fluid shifts. Head down-tilt bed rest (HDBR) is an established spaceflight analog because it mimics microgravity in body unloading and cephalad fluid shifts. Dr. Seidler is currently conducting a prospective longitudinal 70 days 6-degrees HDBR study to investigate the effects of this microgravity analog on brain structure, function, cognition and sensorimotor performance using magnetic resonance imaging (MRI), neuropsychological testing, and sensorimotor performance measures. Preliminary MRI data of this study suggests that bed rest does result in widespread gray matter changes in motor brain regions that furthermore correlate with deterioration in balance performance over the same time course. In consideration of the health of crewmembers and mission success, these results warrant the exploration of countermeasures that prevent or mitigate the effects of brain structure, functional mobility and balance. Exercise interventions in healthy and frail elderly subjects as well as those with neurodegenerative diseases showed that exercise has beneficial effects on cognitive functioning in all these groups. Furthermore, exercise can result in gray matter volume increases that correlate with improvements in cognition, as well as prevention of loss of volume. Therefore, we hypothesized that exercise in bed rest could be a potential countermeasure for the previously observed bed-rest induced brain structural changes and sensorimotor performance deterioration.

Our 70 days 6-degrees HDBR study partially overlapped in participants with a 70 days HDBR study investigating effects of exercise on physical fitness, bone density, and muscle volume that was conducted in the lab of Dr. Ploutz-Snyder. The overlap gave us the unique opportunity to leverage data from both studies to explore the potential mitigating effects of exercise on brain function, structure, functional mobility, standing balance and cognitive performance. Eighteen subjects participated in both studies. Of them, 5 were randomized to a control group. Of the remaining 13 participants, 5 were randomized to a regular aerobic and resistance exercise group and 8 were randomized to a flywheel exercise group. Exercise was practiced in supine position. Regular aerobic exercise consisted of supine treadmill running and cycling. ‘Flywheel’ is an exercise device that is supposed to yield the same beneficial effects on physical fitness in bed rest as regular aerobic supine exercise, but is a compact device and therefore suited to be used in space. Data is currently being analyzed to verify this assumption. Exercise participants started exercising 20 days before the start of bed rest to familiarize themselves with the exercise protocol, and started with the full program from the first day of bed rest until the last day of bed rest. Structural and functional MRI scans and neuropsychological test outcomes were collected at 12 and 8 days prior to HDBR, at day 7, 50, and 70 during HDBR, and 8 and 12 days post-HDBR. Functional mobility and standing balance performance measures were obtained 12 and 8 days prior to HDBR, and directly as well as 8 and 12 days post-HDBR. A variety of physical fitness measures including but not limited to resting metabolic rate, cardiac mass and stroke volume, muscle strength and bone mineral density were repeatedly collected over the course of the study.

In this project, we will address whether the exercise intervention in HDBR affects the course of functional and structural brain changes in bed rest, as well as cognitive functioning and motor performance. State of the art longitudinal neuroimaging processing pipelines and longitudinal voxelwise mixed model analysis techniques are being used to answer this question. Highlighted research questions include: “Does exercise in bed rest change the course of the previously observed volumetric gray matter changes in HDBR?”, “Are pre-bed rest physical fitness measures indicators of functional or structural brain changes over the course of bed rest?”, and “Do both regular aerobic exercise and flywheel exercise mitigate the effects of HDBR on the brain, cognition, and motor performance in a similar fashion?”.

Earth Applications

The results of this study have implications for individuals who are temporarily or permanently bedridden, or to elderly residents of nursing homes with reduced mobility. Individuals who spend a substantial part of the day in a supine position for an extended period of time might be expected to present with similar gray matter and motor performance changes as we observe in HDBR subjects. If exercise proves to be a preventive or mitigating intervention for bed rest effects on brain function and structure, this would justify the exploration of supine exercise interventions on brain function and structure in bedridden individuals.