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At least 19 records

The Effects of Long Duration Bed Rest as a Spaceflight Analogue on Resting State Sensorimotor Network Functional Connectivity and Neurocognitive Performance

Long duration spaceflight has been associated with detrimental alterations in human sensorimotor systems and neurocognitive performance. Prolonged exposure to a head-down tilt position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with neurocognitive performance is largely unknown, but of potential importance to the health and performance of astronauts both during and post-flight. The aims of the present study are 1) to identify changes in sensorimotor resting state functional connectivity that occur with extended bed rest exposure, and to characterize their recovery time course; 2) to evaluate how these neural changes correlate with neurocognitive performance. Resting-state functional magnetic resonance imaging (rsfMRI) data were collected from 17 male participants. The data were acquired through the NASA bed rest facility, located at the University of Texas Medical Branch (Galveston, TX). Participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. RsfMRI data were obtained at seven time points: 7 and 12 days before bed rest; 7, 50, and 65 days during bed rest; and 7 and 12 days after bed rest. Functional connectivity magnetic resonance imaging (fcMRI) analysis was performed to measure the connectivity of sensorimotor networks in the brain before, during, and post-bed rest. We found a decrease in left putamen connectivity with the pre- and post-central gyri from pre bed rest to the last day in bed rest. In addition, vestibular cortex connectivity with the posterior cingulate cortex decreased from pre to post bed rest. Furthermore, connectivity between cerebellar right superior posterior fissure and other cerebellar regions decreased from pre bed rest to the last day in bed rest. In contrast, connectivity within the default mode network remained stable over the course of bed rest. We also utilized a battery of behavioral measures including spatial working memory tasks and measures of functional mobility and balance. These behavioral measurements were collected before, during, and after bed rest. We will report the preliminary findings of correlations observed between brain functional connectivity and behavioral performance changes. Our results suggest that sensorimotor brain networks exhibit decoupling with extended periods of reduced usage. The findings from this study could aid in the understanding and future design of targeted countermeasures to alleviate the detrimental health and neurocognitive effects of long-duration spaceflight.

Cassady, K.↗

The Effects of Long Duration Bed Rest on Functional Mobility and Balance: Relationship to Resting State Motor Cortex Connectivity

NASA offers researchers from a variety of backgrounds the opportunity to study bed rest as an experimental analog for space flight. Extended exposure to a head-down tilt position during long duration bed rest can resemble many of the effects of a low-gravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The aim of our study is to a) identify changes in brain function that occur with prolonged bed rest and characterize their recovery time course; b) assess whether and how these changes impact behavioral and neurocognitive performance. Thus far, we completed data collection from six participants that include task based and resting state fMRI. The data have been acquired through the bed rest facility located at the University of Texas Medical Branch (Galveston, TX). Subjects remained in bed with their heads tilted down 6 degrees below their feet for 70 consecutive days. Behavioral measures and neuroimaging assessments were obtained at seven time points: a) 7 and 12 days before bed rest; b) 7, 30, and 65 days during bed rest; and c) 7 and 12 days after bed rest. Functional connectivity magnetic resonance imaging (FcMRI) analysis was performed to assess the connectivity of motor cortex in and out of bed rest. We found a decrease in motor cortex connectivity with vestibular cortex and the cerebellum from pre bed rest to in bed rest. We also used a battery of behavioral measures including the functional mobility test and computerized dynamic posturography collected before and after bed rest. We will report the preliminary results of analyses relating brain and behavior changes. Furthermore, we will also report the preliminary results of a spatial working memory task and vestibular stimulation during in and out of bed rest.

Erdeniz, B.↗

Exercise Thermoregulation After 6 hours of Chair Rest, 6 deg Head-Down Bed-Rest, and Water Immersion Deconditioning in Men

The purpose was to investigate the mechanism for the excessive exercise hyperthermia following deconditioning (reduction of physical fitness). Rectal (T(sub re)) and mean skin (T(bar)(sub sk)) temperatures and thermoregulatory responses were measured in six men [mean (SD) age, 32 (6) years; mass, 78.26 (5.80) kg; surface area, 1.95 (0.11) sq m; maximum oxygen uptake (VO2max), 48 (6) ml/min/kg; whilst supine in air at dry bulb temperature 23.2 (0.6)C, relative humidity 31.1 (11.1)% and air speed 5.6 (0.1) m/min] during 70 min of leg cycle exercise [51 (4)% VO2max] in ambulatory control (AC), or following 6 h of chair rest (CR), 6deg head-down bed rest (BR), and 20deg (W120) and 80deg (W180) foot-down water immersion [water temperature, 35.0 (0.1) C]. Compared with the AC exercise (Delta)T(sub re) [mean (SD) 0.77 (0.13)C], (Delta)T(sub re), after CR was 0.83 (0.08)C (NS), after BR 0.92 (0.13)C (*P <0.05), after W180 0.96 (0.13)C*, and after W120 1.03 (0.09)C*. All T(sub sk) responded similarly to exercise: they decreased (NS) by 0.5-0.7 C in minutes 4-8 and equilibrated at +0.1 to +0.5 C at 60-70. Skin heat conductance was not different among the five conditions (range = 147-159 kJ/sq/C. Results from an intercorrelation matrix suggested that total body sweat rate was more closely related to T(sub re) at 70 min (T(sub re70)) than limb sweat rate or blood flow. Only 36% of the variability in T(sub re70) could be accounted for by total sweating, and less than 10% from total body dehydration. It would appear that multiple factors are involved which may include change in sensitivity of thermo- and osmoreceptors.

Greenleaf, J. E.↗

Exercise thermoregulation after 6 h of chair rest, 6 degrees head-down bed-rest, and water immersion deconditioning in men

The purpose was to investigate the mechanism for the excessive exercise hyperthermia following deconditioning (reduction of physical fitness). Rectal (Tre) and mean skin (Tsk) temperatures and thermoregulatory responses were measured in six men [mean (SD) age, 32 (6) years; mass, 78.26 (5.80) kg; surface area, 1.95 (0.11) m2; maximum oxygen uptake (VO2max), 48 (6) ml.min-1.kg-1; whilst supine in air at dry bulb temperature 23.2 (0.6) degree C, relative humidity 31.1 (11.1)% and air speed 5.6 (0.1) m.min-1] during 70 min of leg cycle exercise [51 (4)% VO2max] in ambulatory control (AC), or following 6 h of chair rest (CR), 6 degree head-down bed rest (BR), and 20 degree (WI20) and 80 degree (WI80) foot-down water immersion [water temperature, 35.0 (0.1) degree C]. Compared with the AC exercise delta Tre [mean (SD) 0.77 (0.13) degree C (*P < 0.05), after WI80 0.96 (0.13) degree C*, and after WI20 1.03 (0.09) degree C*. All Tsk responded similarly to exercise: they decreased (NS) by 0.5-0.7 degree C in minutes 4-8 and equilibrated at +0.1 to +0.5 degree C at 60-70. Skin heat conductance was not different among the five conditions (range = 147-159 kJ.m-2.h-1.degree C-1). Results from an intercorrelation matrix suggested that total body sweat rate was more closely related to Tre at 70 min (Tre70) than limb sweat rate or blood flow. Only 36% of the variability in Tre70 could be accounted for by total sweating, and less than 10% from total body dehydration. It would appear that multiple factors are involved which may include change in sensitivity of thermo- and osmoreceptors.

NASA Discipline Regulatory Physiology↗

REST Interface Generator (RESTInG) v0.1

From a single data description file, this package generates a simple but complete RESTful web interface to a relational database, in the form of containers that run in a Docker environment. This initial version produces containers that are intended for use on the NERSC Spin platform. It was developed as a foundation for the smart catalog created for LDRD FY20 ACTS: Accelerating COVID-19 Testing with Screening.

Higa, Kenneth↗

Focal Gray Matter Plasticity as a Function of Long Duration Head-down Tilt Bed Rest

Long duration spaceflight (i.e., > or = 22 days) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes may be related to structural and functional brain changes is yet unknown. However, experimental studies revealed changes in the gray matter (GM) of the brain after simulated microgravity. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning and motor behavior. Long duration head-down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on the brain. VBM analysis revealed a progressive decrease from pre- to in- bed rest in GM volume in bilateral areas including the frontal medial cortex, the insular cortex and the caudate. Over the same time period, there was a progressive increase in GM volume in the cerebellum, occipital-, and parietal cortex, including the precuneus. The majority of these changes did not fully recover during the post-bed rest period. Analysis of lobular GM volumes obtained with BRAINS showed significantly increased volume from pre-bed rest to in-bed rest in GM of the parietal lobe and the third ventricle. Temporal GM volume at 70 days in bed rest was smaller than that at the first pre-bed rest measurement. Trend analysis showed significant positive linear and negative quadratic relationships between parietal GM and time, a positive linear relationship between third ventricle volume and time, and a negative linear relationship between cerebellar GM volume and time. FM performance improved from pre-bed rest session 1 to session 2. From the second pre-bed rest measure to the last-day-in-bed rest, there was a significant decrease in performance that only partially recovered post-bed rest. No significant association was observed between changes in brain volume and changes in functional mobility. Extended bed rest, which is an analog for microgravity, can result in local volumetric GM increase and decrease and adversely affect functional mobility. These changes in brain structure and performance were not related in this sample. Whether the effects of bed rest dissipate at longer times post-bed rest, and if they are associated with behavior are important questions that warrant further research including more subjects and longer follow-up times.

Koppelmans, V.↗

Comparison of Ocular Outcomes in Two 14-Day Bed Rest Studies

Reports of astronauts visual changes raised concern about ocular health during long-duration spaceflight. Some of these findings included hyperopic shifts, choroidal folds, optic disc edema, retinal nerve fiber layer (RNFL) thickening, and cotton wool spots. While the etiology remains unknown, hypotheses speculate that hypertension in the brain caused by cephalad fluid shifts during spaceflight is a possible mechanism for these ocular changes. Head-down tilt (HDT) bed rest is a spaceflight analog that induces cephalad fluid shifts. In addition, previous studies of the HDT position demonstrated body fluid shifts associated with changes in intraocular pressure (IOP). For these reasons, vision monitoring of HDT bed rest subjects was implemented for NASA bed rest studies. Subjects selected for these studies were healthy adults (14 males and 5 females). Average age was 37.5 plus or minus 9.1 years, weight was 77.4 plus or minus 11.3 Kg, and height was 173.4 plus or minus 7.2 14 cm. Controlled conditions followed for all NASA bed rest studies were implemented. These conditions included factors such as eating a standardized diet, maintaining a strict sleep wake cycle, and remaining in bed for 24 hours each day. In one study, subjects maintained a horizontal (0 degree) position while in bed and were exercised six days per week with an integrated resistance and aerobic training (iRAT) program. In the other study, subjects were placed at 6 degrees HDT while in bed and did not engage in exercise. All subjects underwent pre- and post bed rest vision testing. While the battery of vision tests for each study was not identical, measures common to both studies will be presented. These measures included IOP and measures that provided an indication of optic disc swelling as derived from optical coherence tomography (OCT) testing: average retinal nerve fiber layer (RNFL) thickness (millimeters), disc area (square millimeters), rim area (square millimters), and average cup to disc (C/D) ratio. For all measures, there was no significant difference between subject groups for pre-bed rest testing. Post bed rest values also remained similar between groups. Comparison of pre- to post bed rest testing within each group did not demonstrate any statistical differences. These preliminary results from 14-day bed rest studies suggest that the combination of exercise and horizontal bed rest as compared to 6 degrees HDT bed rest did not produce differences in the ocular response with regard to IOP and optic disc parameters. The ocular measures reported here only included pre- and post bed rest time points. Further investigation is needed to examine both the acute response and long term adaptation of structural and functional ocular parameters in the bed rest platform and determine its usefulness for studying spaceflight phenomena. From a clinical perspective, the ability to study ocular responses in the controlled environment of the bed rest platform can provide valuable information for the care of patients restricted to bed rest.

Cromwell, R. L.↗

Focal Gray Matter Plasticity as a Function of Long Duration Head Down Tilted Bed Rest: Preliminary Results

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes are solely related to peripheral changes from reduced vestibular stimulation, body unloading, body fluid shifts or that they may be related to structural and functional brain changes is yet unknown. However, a recent study reported associations between microgravity and flattening of the posterior eye globe and protrusion of the optic nerve [1] possibly as the result of increased intracranial pressure due to microgravity induced bodily fluid shifts [3]. Moreover, elevated intracranial pressure has been related to white matter microstructural damage [2]. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning. Long duration head down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system [4]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on brain structure [5]. Here we present results of the first six subjects. Six subjects were assessed at 12 and 7 days before-, at 7, 30, and ~70 days in-, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility in UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1-weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Longitudinal processing in VBM8 includes linear registration of each scan to the mean of the subject and subsequently transforming all scans in to MNI space by applying the warp from the mean subject to MNI to the individual gray matter segmentations. Modulation was applied so that all images represented the volume of the original structure in native space. Voxel wise analysis was carried out on the gray matter images after smoothing, using a flexible factorial design with family wise error correction. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. For each subject, for each DTI metric (i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)), the maximum value in a line perpendicular to the skeleton tract is projected to the skeleton. Non-parametric permutation based t-tests and ANOVA's were used for voxel-wise comparison of the skeletons. For both VBM and TBSS, comparison of pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate (see Figure) from 'pre to in bed rest'. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital-, and parietal cortex, including the precuneus (see Figure). The majority of these changes did not recover from 'during to post bed rest'. TBSS analysis did not reveal significant changes in white matter microstructural integrity after correction for multiple comparisons. Uncorrected analyses (p<.015) revealed an increase in RD in the cerebellum and brainstem from pre bed rest to the first week in bed rest that did not recover post bed rest. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuro motor behavior and cognition. These changes did not recover at two weeks post bed rest. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Koppelmans, V.↗

Exercise Effects on the Brain and Sensorimotor Function in Bed Rest

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.

Koppelmans, V.↗

Effects of Bed Rest on Conduction Velocity of the Triceps Surae Stretch Reflex and Postural Control

Despite rigorous exercise and nutritional management during space missions, astronauts returning from microgravity exhibit neuromuscular deficits and a significant loss in muscle mass in the postural muscles of the lower leg. Similar changes in the postural muscles occur in subjects participating in long-duration bed rest studies. These adaptive muscle changes manifest as a reduction in reflex conduction velocity during head-down bed rest. Because the stretch reflex encompasses both the peripheral (muscle spindle and nerve axon) and central (spinal synapse) components involved in adaptation to calf muscle unloading, it may be used to provide feedback on the general condition of neuromuscular function, and might be used to evaluate the effectiveness of countermeasures aimed at preserving muscle mass and function during periods of unloading. Stretch reflexes were measured on 18 control subjects who spent 60 to 90 days in continuous 6 deg head-down bed rest. Using a motorized system capable of rotating the foot around the ankle joint (dorsiflexion) through an angle of 10 degrees at a peak velocity of about 250 deg/sec, a stretch reflex was recorded from the subject's left triceps surae muscle group. Using surface electromyography, about 300 reflex responses were obtained and ensemble-averaged on 3 separate days before bed rest, 3 to 4 times in bed, and 3 times after bed rest. The averaged responses for each test day were examined for reflex latency and conduction velocity (CV) across gender. Computerized posturography was also conducted on these same subjects before and after bed rest as part of the standard measures. Peak-to-peak sway was measured during Sensory Organization Tests (SOTs) to evaluate changes in the ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Although no gender differences were found, a significant increase in reflex latency and a significant decrease in CV were observed during the bed rest period, with a return to baseline 3 to 5 days after bed rest, depending on the duration of bed rest. In addition, a relationship between CV and loss of muscle strength in the lower leg was observed post bed rest for most subjects. Immediately post-bed rest, most subjects showed decreased performance on SOTs, with the greater decrements on sway-referenced support and head movement conditions. Post-bed rest decrements were less than typically observed following spaceflight. Decrements in postural control and the stretch reflex can be primarily attributed to the unloading mechanisms this ground-based analog provides. The stretch reflex is a concise test measurement that can be obtained during the head-down phase of bed rest, as it does not interfere with the bed rest paradigm. This makes it an ideal tool that can detect, early on, whether a countermeasure is successful in preserving muscle function.

Reschke, M. F.↗

Feasibility Study of a Lunar Analog Bed Rest Model

The purpose of this study was to determine the feasibility of using a 9.5deg head-up tilt bed rest model to simulate the effects of the 1/6 g load to the human body that exists on the lunar surface. The lunar analog bed rest model utilized a modified hospital bed. The modifications included mounting the mattress on a sled that rolled on bearings to provide freedom of movement. The weight of the sled was off-loaded using a counterweight system to insure that 1/6 body weight was applied along the long axis (z-axis) of the body. Force was verified through use of a force plate mounted at the foot of the bed. A seating assembly was added to the bed to permit periods of sitting. Subjects alternated between standing and sitting positions throughout the day. A total of 35% of the day was spent in the standing position and 65% was spent sitting. In an effort to achieve physiologic fluid shifts expected for a 1/6 G environment, subjects wore compression stockings and performed unloaded foot and ankle exercises. Eight subjects (3 females and 5 males) participated in this study. Subjects spent 13 days in the pre-bed rest phase, 6 days in bed rest and 3 days post bed rest. Subjects consumed a standardized diet throughout the study. To determine feasibility, measures of subject comfort, force and plasma volume were collected. Subject comfort was assessed using a Likert scale. Subjects were asked to assess level of comfort (0-100) for 11 body regions and provide an overall rating. Results indicated minimal to no discomfort as most subjects reported scores of zero. Force measures were performed for each standing position and were validated against subject s calculated 1/6 body weight (r(sup 2) = 0.993). The carbon monoxide rebreathing technique was used to assess plasma volume during pre-bed rest and on the last day of bed rest. Plasma volume results indicated a significant decrease (p = 0.001) from pre to post bed rest values. Subjects lost on average 8.3% (sd = 6.1%) during the bed rest phase. Findings from this feasibility study indicated that 1) the lunar analog bed rest model was well tolerated by subjects; 2) a 1/6 load was accurately applied to the z-axis of the body; and 3) plasma volume losses could be achieved in a head-up tilt bed rest model. Future work to refine this model should include extending the duration of bed rest to mimic longer mission durations and a comprehensive assessment of the physiological responses to this bed rest analog.

Cromwell, Ronita L.↗

The Effects of Long Duration Bed Rest on Brain Functional Connectivity and Sensorimotor Functioning

Long duration spaceflight has been associated with detrimental alterations in human sensorimotor functioning. Prolonged exposure to a head-down tilt (HDT) position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with behavior is largely unknown, but of importance to the health and performance of astronauts both during and post-flight. In the present study, we investigate the effects of prolonged exposure to HDT bed rest on resting state brain functional connectivity and its association with behavioral changes in 17 male participants. To validate that our findings were not due to confounding factors such as time or task practice, we also acquired resting state functional magnetic resonance imaging (rs-fMRI) and behavioral measurements from 14 normative control participants at four time points. Bed rest participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. Rs-fMRI and behavioral data were obtained at seven time points averaging around: 12 and 8 days prior to bed rest; 7, 50, and 70 days during bed rest; and 8 and 12 days after bed rest. 70 days of HDT bed rest resulted in significant increases in functional connectivity during bed rest followed by a reversal of changes in the post bed rest recovery period between motor cortical and somatosensory areas of the brain. In contrast, decreases in connectivity were observed between temporoparietal regions. Furthermore, post-hoc correlation analyses revealed a significant relationship between motor-somatosensory network connectivity and standing balance performance changes; participants that exhibited the greatest increases in connectivity strength showed the least deterioration in postural equilibrium with HDT bed rest. This suggests that neuroplastic processes may facilitate adaptation to the HDT bed rest environment. The findings from this study provide novel insights into the neurobiology and future risk assessments of long-duration spaceflight.

Cassady, K.↗

Controlled Rest: Profile of Use, Challenges, and Best Practices

Despite the introduction of flight, duty, and rest time regulations to reduce the risk of sleepiness, airline pilots often encounter elevated sleepiness during flight. To combat this sleepiness, in some instances, pilots can take a short nap on the flight deck (controlled rest) to improve their alertness. Little is known, however, as to when and how often this countermeasure is used operationally. Methods: Forty-four pilots from a European carrier wore actiwatches and filled in an electronic sleep and work diary for approximately 2 weeks resulting in data from 239 flights. Self-reported in-flight rest periods were used to set rest intervals and sleep was estimated within these intervals using Philips Actiware 6.0.9. Wake threshold selection was set to medium; sleep threshold detection algorithm was set to 10 immobile minutes at sleep onset and sleep end. Timing of sleep periods was analyzed relative to home base time. Results: Preliminary analyses showed that controlled rest was taken on 46% (n=110) of flights. On 23 flights (10%) pilots reported taking two controlled rest periods. Sleep, as estimated by actigraphy, was achieved during 80% (n=106) of controlled rest periods. The mean sleep duration was 32 (± 12) minutes estimated within successful controlled rest periods. Approximately two-thirds (67.5%, n=81) of all rest periods were initiated during home base time night (0000h-0800h). On 11% (n=26) of flights, pilots also reported taking bunk rest (longer rest period in a designated sleeping facility).Conclusion:This study shows that controlled rest is commonly used as a countermeasure to sleepiness on the flight deck. Further analysis is required to determine what other factors contribute to the decision to take controlled rest, and how effective it is in reducing sleepiness on the flight deck.

Hilditch, Cassie J.↗

Changes in markers of bone formation and resorption in a bed rest model of weightlessness

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

NASA Discipline Number 26-10↗

Atropine unmasks bed-rest effect - A spectral analysis of cardiac interbeat intervals

Heart rate spectral data obtained for 10 male subjects between 35-49 years following orthostatic tolerance testing with lower body negative pressure prebed rest and after 7-10 days of bed rest, while on placebo and after intravenous atropine are analyzed. Comparison of the spectral atropine rms for subjects prebed rest and after bed rest reveal a decrease from 63 + or - 24 ms to 40 + or - 23 ms. It is observed that heart rate interval variability for subjects after bed rest and with atropine is reduced; the heart rate at bed rest with atropine is increased from 70.4 + or - 12.4 beats/min prebed rest to 83.7 + or - 18.9 beats/min; and the exercise tolerance time for subjects in the atropine prebed-rest phase (658 + or - 352 s) is higher than the bed-rest phase (505 + or - 252 s). It is noted that bed rest impairs the cardiovascular capacity to adaptively modulate physiological responses, atropine exposes bed-rest deconditioning effects, and spectral analysis is useful for studying the effects of bed-rest deconditioning on cardiac dynamics.

Goldberger, Ary L.↗

Cardiovascular Adaptations to Long Duration Head-Down Tilt Bed Rest

INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 days of bed rest, and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 minutes or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49. Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Intimal-medial thickness markedly decreased at bed rest days 21, 35 and 49. Several cardiac functional parameters including isovolumic relaxation time, ejection time and myocardial performance index were significantly increased (indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 days of bed rest. DISCUSSION: These data suggest that 6 head-down tilt bed rest alters cardiovascular structure and function in a pattern similar to short duration spaceflight. Additionally, the vascular alterations are primarily seen in the lower body, while vessels of the upper body are unaffected. KEY WORDS: spaceflight, orthostatic intolerance, hypotension, fluid-shift, plasma volume

Platts, Steven H.↗

Association Between Cardiovascular and Intraocular Pressure Changes in a 14-Day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

Visual symptoms and intracranial pressure increase reported in astronauts returning from long duration missions in low Earth-orbit are thought to be related to fluid shifts within the body due to microgravity exposure. Because of this possible relation to fluid shifts, studies conducted in head-down tilt (HDT) bed rest are being monitored for potential changes in ocular health. These measures will also serve to determine whether HDT is a suitable ground-based analog to model subclinical cardiovascular and ocular changes that could shed light on the etiology of the VIIP syndrome observed in spaceflight. Sixteen healthy normotensive (12M, 4F, age range 29-54 years), non-smoker and normal weight subjects, volunteered to participate in a 14 day 6 deg head HDT study conducted at the NASA Flight Analogs Research Unit (FARU). This facility provides standard bed rest conditions (diet, wake/sleep time, time allowed in sunlight) during the time that the subjects stay at the FARU. Cardiovascular parameters were obtained in supine posture at BR-5, BR+0, and BR+3 and ocular monitoring was performed weekly. Intraocular pressure (IOP) increased from pre-bed rest BR-3) to the third day into bed rest (BR+3). Values reached a plateau towards the end of the bed rest phase (BR10) and decreased within the first three days of recovery (BR+2) returning to levels comparable to baseline at BR-3. As expected, most cardiovascular parameters were affected by 14 days of HDT bed rest. Plasma volume decreased as a result of bed rest but recovered to baseline levels by BR+3. Indications of cardiovascular deconditioning included increase in both systolic and diastolic blood pressure and heart rate, and a decrease in stroke volume and cardiac output between BR-5 and BR+3. Due to the experimental design of this study, we were not able to test the hypothesis that fluid shifts might be involved in the IOP increase during the bed rest phase, since cardiovascular measures were not available for those time points. There was no correlation between the largest change in IOP (BR-3 versus BR3) and cardiovascular measure changes between baseline (BR-5) and post bed rest (BR+2). While no clinically relevant visual changes were observed during the study, measurement of various retinal parameters was performed with optical coherence tomography (OCT). A decrease in central subfield retinal thickness was observed between BR+2 and baseline at BR-10, but no association was observed with IOP changes. This work investigates the time course of changes in IOP during 14-day HDT bed rest in an attempt to characterize HDT bed rest as a model of the VIIP syndrome and delve into its etiology.

Cromwell, Ronita↗