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Koppelmans, V.

Publications and source records attributed to Koppelmans, V..

Sensorimotor Predictors of Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can potentially be used to predict early performance following G-transitions such as return to Earth on a set of sensorimotor tasks. Astronauts are being recruited who previously participated in sensorimotor field tests and/or dynamic posturography (MedB) within R+1 days following long-duration spaceflight.

Wood, S. J.↗

Long Duration Head Down Tilt Bed Rest and Spaceflight Effects on Neurocognitive Performance: Extent, Longevity and Neural Bases

We have recently completed a long duration head down tilt bed rest (HDBR) study in which we performed structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations in a spaceflight analog environment. We are also collecting the same measures in crewmembers prior to and following a six month International Space Station mission. We will present data demonstrating that bed rest resulted in functional mobility and balance deterioration with recovery post-HDBR. We observed numerous changes in brain structure, function, and connectivity relative to a control group which were associated with pre to post bed rest changes in sensorimotor function. For example, gray matter volume (GMv) increased in posterior parietal areas and decreased in frontal regions. GMv increases largely overlapped with fluid decreases and vice versa. Larger increases in precentral gyrus (M1)/ postcentral gyrus (S1+2) GMv and fluid decreases were associated with smaller balance decrements. Vestibular activation in the bilateral insular cortex increased with bed rest and subsequently recovered. Larger increases in vestibular activation in multiple brain regions were associated with greater decrements in balance and mobility. We found connectivity increases between left M1 with right S1+2 and the superior parietal lobule, and right vestibular cortex with the cerebellum. Decreases were observed between right Lobule VIII with right S1+2 and the supramarginal gyrus, right posterior parietal cortex (PPC) with occipital regions, and the right superior posterior fissure with right Crus I and II. Connectivity strength between left M1 and right S1+2/superior parietal lobule increased the most in individuals that exhibited the least balance impairments. In sum, we observed HDBR-related changes in measures of brain structure, function, and network connectivity, which correlated with indices of sensorimotor function. Recovery was observed post HDBR but remained incomplete at 12 days post-HDBR. Preliminary findings from our parallel ongoing flight study will be compared and contrasted with bed rest results during this presentation.

Seidler, R. D.↗

Spaceflight Effects on Neurocognitive Performance: Extent, Longevity and Neural Bases

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post spaceflight. Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that are conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. We have collected data on several crewmembers and preliminary findings will be presented. Eventual comparison to results from our parallel bed rest study will enable us to parse out the multiple mechanisms contributing to any spaceflight-induced neural structural and behavioral changes that we observe.

Seidler, R. D.↗

Effects of One Year of Spaceflight on Neurocognitive Function

It is known that spaceflight adversely affects human sensorimotor function. With interests in longer duration deep space missions it is important to understand microgravity dose-response relationships. NASA's One Year Mission project allows for comparison of the effects of one year in space with those seen in more typical six month missions to the International Space Station. In the Neuromapping project we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre- to post-spaceflight. Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad-ranging battery of sensory, motor, and cognitive assessments that are conducted pre-flight, during flight, and post-flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. With the one year mission we had one crewmember participate in all of the same measures pre-, per- and post-flight as in our ongoing study. During this presentation we will provide an overview of the magnitude of changes observed with our brain and behavioral assessments for the one year crewmember in comparison to participants that have completed our six month study to date.

Seidler, R. D.↗

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.↗

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.↗

Increased Brain Activation for Foot Movement During 70-Day 6 Deg Head-Down Bed Rest (HDBR): Evidence from Functional Magnetic Resonance Imaging (fMRI)

Bed rest has been widely used as a simulation of weightlessness in studying the effects of microgravity exposure on human physiology and cognition. Changes in muscle function and functional mobility have been reported to be associated with bed rest. Understanding the effect of bed rest on neural control of movement would provide helpful information for spaceflight. In the current study, we evaluated how the brain activation for foot movement changed as a function of bed rest. Eighteen healthy men (aged 25 to 39 years) participated in this HDBR study. They remained continuously in the 6deg head‐down tilt position for 70 days. Functional MRI was acquired during 1‐Hz right foot tapping, and repeated at 7 time points: 12 days pre‐, 8 days pre‐, 7 days in‐, 50 days in‐, 70 days in‐, 8 days post‐, and 12 days post‐ HDBR. In all 7 sessions, we observed increased activation in the left motor cortex, right cerebellum and right occipital cortex during foot movement blocks compared to rest. Compared to the pre‐HDBR baseline (1st and 2nd sessions), foot movement‐induced activation in the left hippocampus increased during HDBR. This increase emerged in the 4th session, enlarged in the 5th session, and remained significant in the 6th and 7th sessions. Furthermore, increased activation relative to the baseline in left precuneus was observed in the 5th, 6th and 7th sessions. In addition, in comparison with baseline, increased activation in the left cerebellum was found in the 4th and 5th sessions, whereas increased activation in the right cerebellum was observed in the 4th, 6th and 7th sessions. No brain region exhibited decreased activation during bed rest compared to baseline. The increase of foot movement related brain activation during HDBR suggests that in a long‐term head‐down position, more neural control is needed to accomplish foot movements. This change required a couple of weeks to develop in HDBR (between 3rd and 4th sessions), and did not return to baseline even 12 days after HDBR. The observed effect of bed rest on brain activation during a foot tapping task could be linked to HDBR related changes in brain structure that we have recently reported. The relationship between pre‐ and post‐ HDBR changes in brain activation and performance in a functional mobility test will also be presented.

Yuan, P.↗

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.↗

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.↗

Focal Gray Matter Plasticity as a Function of Long Duration Bedrest: 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. It is unknown whether and how spaceflight impacts sensorimotor brain structure and function, and whether such changes may potentially underlie behavioral effects. Long duration head down tilt bed rest has been used repeatedly as an exclusionary analog to study microgravity effects on the sensorimotor system [1]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. We are currently testing sensorimotor function, brain structure, and brain function pre and post a 70‐day bed rest period. We will acquire the same measures on NASA crewmembers starting in 2014. Here we present the results of the first eight bed rest subjects. 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, 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. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of the 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. 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 the two 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 nucleus 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 cortices. The majority of these changes did not recover from during to post bed rest. TBSS analyses will also be presented. 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 neuromotor behavior and cognition. These changes did not recover at two weeks post bed rest. These results have significant public health implications, and will also aid in interpretation of our future data obtained pre and post spaceflight. 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.↗

Customizing Countermeasure Prescriptions using Predictive Measures of Sensorimotor Adaptability

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the readapation phase following a return to a gravitational environment. These alterations may lead to disruption in the ability to perform mission critical functional tasks during and after these gravitational transitions. Astronauts show significant inter-subject variation in adaptive capability following gravitational transitions. The ability to predict the manner and degree to which each individual astronaut will be affected would improve the effectiveness of a countermeasure comprised of a training program designed to enhance sensorimotor adaptability. Due to this inherent individual variability we need to develop predictive measures of sensorimotor adaptability that will allow us to predict, before actual space flight, which crewmember will experience challenges in adaptive capacity. Thus, obtaining this information will allow us to design and implement better sensorimotor adaptability training countermeasures that will be customized for each crewmember's unique adaptive capabilities. Therefore the goals of this project are to: 1) develop a set of predictive measures capable of identifying individual differences in sensorimotor adaptability, and 2) use this information to design sensorimotor adaptability training countermeasures that are customized for each crewmember's individual sensorimotor adaptive characteristics. To achieve these goals we are currently pursuing the following specific aims: Aim 1: Determine whether behavioral metrics of individual sensory bias predict sensorimotor adaptability. For this aim, subjects perform tests that delineate individual sensory biases in tests of visual, vestibular, and proprioceptive function. Aim 2: Determine if individual capability for strategic and plastic-adaptive responses predicts sensorimotor adaptability. For this aim, each subject's strategic and plastic-adaptive motor learning abilities are assessed using a test of locomotor function designed specifically to delineate both mechanisms. Aim 3: Develop predictors of sensorimotor adaptability using brain structural and functional metrics. We will measure 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). We decided to complete the data collection for Specific Aims 1, 2 and 3 simultaneously on the same subjects to increase data capture. By having the same subjects perform all three specific aims we can enhance our ability to detect how a wider range of factors can predict adaptability in a specific individual. This provides a much richer database and potentially a better understanding of the predictive power of the selected factors. In this presentation I will discuss preliminary data obtained to date.

Bloomberg, J. J.↗

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.↗

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.↗

The Effects of Long Duration Head Down Tilt Bed Rest on Neurocognitive Performance: The Effects of Exercise Interventions

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. Our ongoing bed rest participants are also engaging in exercise studies directed by Dr. Lori Ploutz Snyder. In this presentation, I will briefly highlight the existing literature linking exercise and fitness to brain and behavioral functions. I will also overview the metrics from my study that could be investigated in relation to the exercise and control subgroups.

Seidler, R. D.↗

The Effects of Spaceflight and a Spaceflight Analog on Neurocognitive Perfonnance: Extent, Longevity, and Neural Bases

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. With the bedrest study, we will be able to determine the neural and neurocognitive effects of extended duration unloading, reduced sensory inputs, and increased cephalic fluid distribution. This will enable us to parse out the multiple mechanisms contributing to any spaceflight-induced neural structural and behavioral changes that we observe in the flight study. In this presentation I will discuss preliminary results from six participants who have undergone the bed rest protocol. These individuals show decrements in balance and functional mobility, and alterations in brain structure and function, in association with extended bed rest.

Seidler, R. D.↗

Exercise Effects on the Course of Gray Matter Changes Over 70 Days of Bed Rest

Long duration spaceflight affects posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes through direct effects on peripheral changes that result from reduced vestibular stimulation and body unloading. Effects of microgravity on sensorimotor function have been investigated on earth using bed rest studies. Long duration bed rest serves as a space-flight analogue because it mimics microgravity in body unloading and bodily fluid shifts. It has been hypothesized that the cephalad fluid shift that has been observed in microgravity could potentially affect central nervous system function and structure, and thereby indirectly affect sensorimotor or cognitive functioning. Preliminary results of one of our ongoing studies indeed showed that 70 days of long duration head down-tilt bed rest results in focal changes in gray matter volume from pre-bed rest to various time points during bed rest. These gray matter changes that could reflect fluid shifts as well as neuroplasticity were related to decrements in motor skills such as maintenance of equilibrium. In consideration of the health and performance of crewmembers both inand post-flight we are currently conducting a study that investigates the potential preventive effects of exercise on gray matter and motor performance changes that we observed over the course of bed rest. Numerous studies have shown beneficial effects of aerobic exercise on brain structure and cognitive performance in healthy and demented subjects over a large age range. We therefore hypothesized that an exercise intervention in bed rest could potentially mitigate or prevent the effects of bed rest on the central nervous system. Here we present preliminary outcomes of our study.

Koppelmans, V.↗