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Abstract During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

IntroductionWalking in complex environments increases the cognitive demand of locomotor control; however, our understanding of the neural mechanisms contributing to walking on uneven terrain is limited. We used a novel method for altering terrain unevenness on a treadmill to investigate the association between terrain unevenness and cortical activity in the prefrontal cortex, a region known to be involved in various cognitive functions.MethodsPrefrontal cortical activity was measured with functional near infrared spectroscopy while participants walked on a novel custom-made terrain treadmill surface across four different terrains: flat, low, medium, and high levels of unevenness. The assessments were conducted in younger adults, older adults with better mobility function and older adults with worse mobility function. Mobility function was assessed using the Short Physical Performance Battery. The primary hypothesis was that increasing the unevenness of the terrain would result in greater prefrontal cortical activation in all groups. Secondary hypotheses were that heightened prefrontal cortical activation would be observed in the older groups relative to the younger group, and that prefrontal cortical activation would plateau at higher levels of terrain unevenness for the older adults with worse mobility function, as predicted by the Compensation Related Utilization of Neural Circuits Hypothesis.ResultsThe results revealed a significant main effect of terrain, indicating a significant increase in prefrontal cortical activation with increasing terrain unevenness during walking in all groups. A significant main effect of group revealed that prefrontal cortical activation was higher in older adults with better mobility function compared to younger adults and older adults with worse mobility function in all pooled terrains, but there was no significant difference in prefrontal cortical activation between older adults with worse mobility function and younger adults. Contrary to our hypothesis, the older group with better mobility function displayed a sustained increase in activation but the other groups did not, suggestive of neural compensation. Additional findings were that task-related increases in prefrontal cortical activation during walking were lateralized to the right hemisphere in older adults with better mobility function but were bilateral in older adults with worse mobility function and younger adults.DiscussionThese findings support that compared to walking on a flat surface, walking on uneven terrain surfaces increases demand on cognitive control resources as measured by prefrontal cortical activation.

Walking performance and cognitive function demonstrate strong associations in older adults, with both declining with advancing age. Walking requires the use of cognitive resources, particularly in complex environments like stepping over obstacles. A commonly implemented approach for measuring the cognitive control of walking is a dual-task walking assessment, in which walking is combined with a second task. However, dual-task assessments have shortcomings, including issues with scaling the task difficulty and controlling for task prioritization. Here we present a new assessment designed to be less susceptible to these shortcomings while still challenging cognitive control of walking: the Obstructed Vision Obstacle (OBVIO) task. During the task, participants hold a lightweight tray at waist level obstructing their view of upcoming foam blocks, which are intermittently spaced along a 10 m walkway. This forces the participants to use cognitive resources (e.g., attention and working memory) to remember the exact placement of upcoming obstacles to facilitate successful crossing. The results demonstrate that adding the obstructed vision board significantly slowed walking speed by an average of 0.26 m/s and increased the number of obstacle strikes by 8-fold in healthy older adults (n = 74). Additionally, OBVIO walking performance (a score based on both speed and number of obstacle strikes) significantly correlated with computer-based assessments of visuospatial working memory, attention, and verbal working memory. These results provide initial support that the OBVIO task is a feasible walking test that demands cognitive resources. This study lays the groundwork for using the OBVIO task in future assessment and intervention studies.

Abstract Spaceflight induces widespread changes in human brain morphology. It is unclear if these brain changes differ with varying mission duration or spaceflight experience history (i.e., novice or experienced, number of prior missions, time between missions). Here we addressed this issue by quantifying regional voxelwise changes in brain gray matter volume, white matter microstructure, extracellular free water (FW) distribution, and ventricular volume from pre- to post-flight in a sample of 30 astronauts. We found that longer missions were associated with greater expansion of the right lateral and third ventricles, with the majority of expansion occurring during the first 6 months in space then appearing to taper off for longer missions. Longer inter-mission intervals were associated with greater expansion of the ventricles following flight; crew with less than 3 years of time to recover between successive flights showed little to no enlargement of the lateral and third ventricles. These findings demonstrate that ventricle expansion continues with spaceflight with increasing mission duration, and inter-mission intervals less than 3 years may not allow sufficient time for the ventricles to fully recover their compensatory capacity. These findings illustrate some potential plateaus in and boundaries of human brain changes with spaceflight.

Accuracy of electroencephalography (EEG) source localization relies on the volume conduction head model. A previous analysis of young adults has shown that simplified head models have larger source localization errors when compared with head models based on magnetic resonance images (MRIs). As obtaining individual MRIs may not always be feasible, researchers often use generic head models based on template MRIs. It is unclear how much error would be introduced using template MRI head models in older adults that likely have differences in brain structure compared to young adults. The primary goal of this study was to determine the error caused by using simplified head models without individual-specific MRIs in both younger and older adults. We collected high-density EEG during uneven terrain walking and motor imagery for 15 younger (22±3 years) and 21 older adults (74±5 years) and obtained $\text{T}_{{1}}$ -weighted MRI for each individual. We performed equivalent dipole fitting after independent component analysis to obtain brain source locations using four forward modeling pipelines with increasing complexity. These pipelines included: 1) a generic head model with template electrode positions or 2) digitized electrode positions, 3) individual-specific head models with digitized electrode positions using simplified tissue segmentation, or 4) anatomically accurate segmentation. We found that when compared to the anatomically accurate individual-specific head models, performing dipole fitting with generic head models led to similar source localization discrepancies (up to 2 cm) for younger and older adults. Co-registering digitized electrode locations to the generic head models reduced source localization discrepancies by $\sim $ 6 mm. Additionally, we found that source depths generally increased with skull conductivity for the representative young adult but not as much for the older adult. Our results can help inform a more accurate interpretation of brain areas in EEG studies when individual MRIs are unavailable.

Spaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated whether AG alters resting-state brain functional connectivity changes during head-down tilt bed rest (HDBR), a spaceflight analog. Participants underwent 60 days of HDBR. Two groups received daily AG administered either continuously (cAG) or intermittently (iAG). A control group received no AG. We assessed resting-state functional connectivity before, during, and after HDBR. We also measured balance and mobility changes from pre- to post-HDBR. We examined how functional connectivity changes throughout HDBR and whether AG is associated with differential effects. We found differential connectivity changes by group between posterior parietal cortex and multiple somatosensory regions. The control group exhibited increased functional connectivity between these regions throughout HDBR whereas the cAG group showed decreased functional connectivity. This finding suggests that AG alters somatosensory reweighting during HDBR. We also observed brain-behavioral correlations that differed significantly by group. Control group participants who showed increased connectivity between the putamen and somatosensory cortex exhibited greater mobility declines post-HDBR. For the cAG group, increased connectivity between these regions was associated with little to no mobility declines post-HDBR. This suggests that when somatosensory stimulation is provided via AG, functional connectivity increases between the putamen and somatosensory cortex are compensatory in nature, resulting in reduced mobility declines. Given these findings, AG may be an effective countermeasure for the reduced somatosensory stimulation that occurs in both microgravity and HDBR.

Abstract Humans are exposed to extreme environmental stressors during spaceflight and return with alterations in brain structure and shifts in intracranial fluids. To date, no studies have evaluated the effects of spaceflight on perivascular spaces (PVSs) within the brain, which are believed to facilitate fluid drainage and brain homeostasis. Here, we examined how the number and morphology of magnetic resonance imaging (MRI)-visible PVSs are affected by spaceflight, including prior spaceflight experience. Fifteen astronauts underwent six T 1-weighted 3 T MRI scans, twice prior to launch and four times following their return to Earth after ~ 6-month missions to the International Space Station. White matter MRI-visible PVS number and morphology were calculated using an established, automated segmentation algorithm. We validated our automated segmentation algorithm by comparing algorithm PVS counts with those identified by two trained raters in 50 randomly selected slices from this cohort; the automated algorithm performed similarly to visual ratings (r(48) = 0.77, p 0.50). Among the astronaut cohort, we found that novice astronauts showed an increase in total PVS volume from pre- to post-flight, whereas experienced crewmembers did not (p = 0.020), suggesting that experienced astronauts may exhibit holdover effects from prior spaceflight(s). Greater pre-flight PVS load was associated with more prior flight experience (r = 0.60–0.71), though these relationships did not reach statistical significance (p > 0.05). Pre- to post-flight changes in ventricular volume were not significantly associated with changes in PVS characteristics, and the presence of spaceflight associated neuro-ocular syndrome (SANS) was not associated with PVS number or morphology. Together, these findings demonstrate that PVSs can be consistently identified on T 1-weighted MRI scans, and that spaceflight is associated with PVS changes. Specifically, prior spaceflight experience may be an important factor in determining PVS characteristics.

IntroductionWhy do people help strangers? Prior research suggests that empathy motivates bystanders to respond to victims in distress. However, this work has revealed relatively little about the role of the motor system in human altruism, even though altruism is thought to have originated as an active, physical response to close others in immediate need. We therefore investigated whether a motor preparatory response contributes to costly helping.MethodsTo accomplish this objective, we contrasted three charity conditions that were more versus less likely to elicit an active motor response, based on the Altruistic Response Model. These conditions described charities that (1) aided neonates versus adults, (2) aided victims requiring immediate versus preparatory support, and (3) provided heroic versus nurturant aid. We hypothesized that observing neonates in immediate need would elicit stronger brain activation in motor-preparatory regions.ResultsConsistent with an evolutionary, caregiving-based theory of altruism, participants donated the most to charities that provided neonates with immediate, nurturant aid. Critically, this three-way donation interaction was associated with increased BOLD signal and gray matter volume in motor-preparatory regions, which we identified in an independent motor retrieval task.DiscussionThese findings advance the field of altruism by shifting the spotlight from passive emotional states toward action processes that evolved to protect the most vulnerable members of our group.

IntroductionCooperation and competition are common in social interactions. It is not clear how individual differences in personality may predict performance strategies under these two contexts. We evaluated whether instructions to play cooperatively and competitively would differentially affect dyads playing a Pong video game. We hypothesized that instructions to play cooperatively would result in lower overall points scored and differences in paddle control kinematics relative to when participants were instructed to play competitively. We also predicted that higher scores in prosociality and Sportspersonship would be related to better performance during cooperative than competitive conditions.MethodsPairs of participants played a Pong video game under cooperative and competitive instructions. During competitive trials, participants were instructed to score more points against one another to win the game. During the cooperative trials, participants were instructed to work together to score as few points against one another as possible. After game play, each participant completed surveys so we could measure their trait prosociality and Sportspersonship.ResultsCondition was a significant predictor of where along the paddle participants hit the ball, which controlled ball exit angles. Specifically, during cooperation participants concentrated ball contacts on the paddle towards the center to produce more consistent rebound angles. We found a significant correlation of Sex and the average points scored by participants during cooperative games, competitive games, and across all trials. Sex was also significantly correlated with paddle kinematics during cooperative games. The overall scores on the prosociality and Sportspersonship surveys were not significantly correlated with the performance outcomes in cooperative and competitive games. The dimension of prosociality assessing empathic concern was significantly correlated with performance outcomes during cooperative video game play.DiscussionNo Sportspersonship survey score was able to predict cooperative or competitive game performance, suggesting that Sportspersonship personality assessments are not reliable predictors of cooperative or competitive behaviors translated to a virtual game setting. Survey items and dimensions probing broader empathic concern may be more effective predictors of cooperative and competitive performance during interactive video game play. Further testing is encouraged to assess the efficacy of prosocial personality traits as predictors of cooperative and competitive video game behavior.

IntroductionPeople exhibit a strong attachment to possessions, observed in behavioral economics through loss aversion using new items in the Endowment or IKEA effects and in clinical psychology through pathological trouble discarding domestic items in Hoarding Disorder. These fields rarely intersect, but both document a reticence to relinquish a possessed item, even at a cost, which is associated with feelings of loss but can include enhanced positive states as well.MethodsTo demonstrate the shared properties of these loss-related ownership effects, we developed the Pretzel Decorating Task (PDT), which concurrently measures overvaluation of one’s own over others’ items and feelings of loss associated with losing a possession, alongside enhanced positive appraisals of one’s items and an effort to save them. The PDT was piloted with 31 participants who decorated pretzels and responded to their own or others’ items during functional neuroimaging (fMRI). Participants observed one item per trial (self or other) and could work to save it (high or low probability loss) before learning the fate of the item (trashed or saved). Finally, participants rated items and completed hoarding tendency scales.ResultsThe hypotheses were supported, as even non-clinical participants overvalued, viewed as nicer, feared losing, and worked harder to save their items over others’—a response that correlated with hoarding tendencies and motor-motivational brain activation. Our region of interest in the nucleus accumbens (NAcc) was engaged when viewing one’s own items to the extent that people worked harder to save them and was more active when their items were saved when they felt emotionally attached to possessions in real life. When their items were trashed, NAcc activity negatively correlated with trouble discarding and emotional attachments to possessions. Right anterior insula was more active when working to save one’s own over others’ items. Extensive motor-motivational areas were engaged when working to save one’s own over others’ items, including cerebellum, primary motor and somatosensory regions, and retrosplenial/parahippocampal regions—even after controlling for tapping.DiscussionOur attachments to items are emotional, continuous across typical and pathological populations, and drive us to save possessions that we value.

A team of experts on the effects of the spaceflight environment on the brain and eye (SANS: Spaceflight-Associated Neuro-ocular Syndrome) was convened by NASA and ESA to (1) review spaceflight-associated structural and functional changes of the human brain and eye, and any interactions between the two; and (2) identify critical future research directions in this area to help characterize the risk and identify possible countermeasures and strategies to mitigate the spaceflight-induced brain and eye alterations. The experts identified 14 critical future research directions that would substantially advance our knowledge of the effects of spending prolonged periods of time in the spaceflight environment on SANS, as well as brain structure and function. They used a paired comparison approach to rank the relative importance of these 14 recommendations, which are discussed in detail in the main report and are summarized briefly below.

The altered vestibular signaling and somatosensory unloading of microgravity result in sensory reweighting and adaptation to conflicting sensory inputs. Aftereffects of these adaptive changes are evident postflight as impairments in behaviors such as balance and gait. Microgravity also induces fluid shifts toward the head and an upward shift of the brain within the skull; these changes are well-replicated in strict head-down tilt bed rest (HDBR), a spaceflight analog environment. Artificial gravity (AG) is a potential countermeasure to mitigate these effects of microgravity. A previous study demonstrated that intermittent (six, 5-mins bouts per day) daily AG sessions were more efficacious at counteracting orthostatic intolerance in a 5 day HDBR study than continuous daily AG. Here we examined whether intermittent daily AG was also more effective than continuous dosing for mitigating brain and behavioral changes in response to 60 days of HDBR. Participants (n = 24) were split evenly between three groups. The first received 30 mins of continuous AG daily (cAG). The second received 30 mins of intermittent AG daily (6 bouts of 5 mins; iAG). The third received no AG (Ctrl). We collected a broad range of sensorimotor, cognitive, and brain structural and functional assessments before, during, and after the 60 days of HDBR. We observed no significant differences between the three groups in terms of HDBR-associated changes in cognition, balance, and functional mobility. Interestingly, the intermittent AG group reported less severe motion sickness symptoms than the continuous group during centrifugation; iAG motion sickness levels were not elevated above those of controls who did not undergo AG. They also had a shorter duration of post-AG illusory motion than cAG. Moreover, the two AG groups performed the paced auditory serial addition test weekly while undergoing AG; their performance was more accurate than that of controls, who performed the test while in HDBR. Although AG did not counteract HDBR-induced gait and balance declines, iAG did not cause motion sickness and was associated with better self-motion perception during AG ramp-down. Additionally, both AG groups had superior cognitive performance while undergoing AG relative to controls; this may reflect attention or motivation differences between the groups.

Almost 25% of all older adults experience difficulty walking. Mobility difficulties for older adults are more pronounced when they perform a simultaneous cognitive task while walking (i.e., dual task walking). Although it is known that aging results in widespread brain atrophy, few studies have integrated across more than one neuroimaging modality to comprehensively examine the structural neural correlates that may underlie dual task walking in older age. We collected spatiotemporal gait data during single and dual task walking for 37 young (18–34 years) and 23 older adults (66–86 years). We also collected T1-weighted and diffusion-weighted MRI scans to determine how brain structure differs in older age and relates to dual task walking. We addressed two aims: (1) to characterize age differences in brain structure across a range of metrics including volumetric, surface, and white matter microstructure; and (2) to test for age group differences in the relationship between brain structure and the dual task cost (DTcost) of gait speed and variability. Key findings included widespread brain atrophy for the older adults, with the most pronounced age differences in brain regions related to sensorimotor processing. We also found multiple associations between regional brain atrophy and greater DTcost of gait speed and variability for the older adults. The older adults showed a relationship of both thinner temporal cortex and shallower sulcal depth in the frontal, sensorimotor, and parietal cortices with greater DTcost of gait. Additionally, the older adults showed a relationship of ventricular volume and superior longitudinal fasciculus free-water corrected axial and radial diffusivity with greater DTcost of gait. These relationships were not present for the young adults. Stepwise multiple regression found sulcal depth in the left precentral gyrus, axial diffusivity in the superior longitudinal fasciculus, and sex to best predict DTcost of gait speed, and cortical thickness in the superior temporal gyrus to best predict DTcost of gait variability for older adults. These results contribute to scientific understanding of how individual variations in brain structure are associated with mobility function in aging. This has implications for uncovering mechanisms of brain aging and for identifying target regions for mobility interventions for aging populations.

Aging is associated with declines in sensorimotor function. Several studies have demonstrated that transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, can be combined with training to mitigate age-related cognitive and motor declines. However, in some cases, the application of tDCS disrupts performance and learning. Here, we applied anodal tDCS either over the left prefrontal cortex (PFC), right PFC, supplementary motor complex (SMC), the left M1, or in a sham condition while older adults (n = 63) practiced a Discrete Sequence Production (DSP), an explicit motor sequence, task across 3 days. We hypothesized that stimulation to either the right or left PFC would enhance motor learning for older adults, based on the extensive literature showing increased prefrontal cortical activity during motor task performance in older adults. Contrary to our predictions, stimulation to the right and left PFC resulted in slowed motor learning, as evidenced by a slower reduction rate of reduction of reaction time and the number of sequence chunks across trials relative to sham in session one and session two, respectively. These findings suggest an integral role of the right PFC early in sequence learning and a role of the left PFC in chunking in older adults, and contribute to mounting evidence of the difficultly of using tDCS in an aging population.

We developed a method for altering terrain unevenness on a treadmill to study gait kinematics. Terrain consisted of rigid polyurethane disks (12.7 cm diameter, 1.3-3.8 cm tall) which attached to the treadmill belt using hook-and-loop fasteners. Here, we tested four terrain unevenness conditions: Flat, Low, Medium, and High. The main objective was to test the hypothesis that increasing the unevenness of the terrain would result in greater gait kinematic variability. Seventeen younger adults (age 20-40 years), 25 higher-functioning older adults (age 65+ years), and 29 lower-functioning older adults (age 65+ years, Short Physical Performance Battery score < 10) participated. We customized the treadmill speed to each participant's walking ability, keeping the speed constant across all four terrain conditions. Participants completed two 3-minute walking trials per condition. Using an inertial measurement unit placed over the sacrum and pressure sensors in the shoes, we calculated the stride-to-stride variability in step duration and sacral excursion (coefficient of variation; standard deviation expressed as percentage of the mean). Participants also self-reported their perceived stability for each condition. Terrain was a significant predictor of step duration variability, which roughly doubled from Flat to High terrain for all participant groups: younger adults (Flat 4.0%, High 8.2%), higher-functioning older adults (Flat 5.0%, High 8.9%), lower-functioning older adults (Flat 7.0%, High 14.1%). Similarly, all groups exhibited significant increases in sacral excursion variability for the Medium and High uneven terrain conditions, compared to Flat. Participants were also significantly more likely to report feeling less stable walking over all three uneven terrain conditions compared to Flat. These findings support the hypothesis that altering terrain unevenness on a treadmill will increase gait kinematic variability and reduce perceived stability in younger and older adults.

Spaceflight induces lasting enlargement of the brain's ventricles as well as intracranial fluid shifts. These intracranial fluid shifts have been attributed to prolonged microgravity exposure, however, the potential effects of hypergravity exposure during launch and landing have yet to be elucidated. Here we describe a case report of a Crewmember who experienced an Aborted Launch (“CAL”). CAL's launch and landing experience was dissociated from prolonged microgravity exposure. Using MRI, we show that hypergravity exposure during the aborted launch did not induce lasting ventricular enlargement or intracranial fluid shifts resembling those previously reported with spaceflight. This case study therefore rules out hypergravity during launch and landing as a contributing factor to previously reported long-lasting intracranial fluid changes following spaceflight.

Astronauts returning from spaceflight typically show transient declines in mobility and balance. Other sensorimotor behaviors and cognitive function have not been investigated as much. Here, we tested whether spaceflight affects performance on various sensorimotor and cognitive tasks during and after missions to the International Space Station (ISS). We obtained mobility (Functional Mobility Test), balance (Sensory Organization Test-5), bimanual coordination (bimanual Purdue Pegboard), cognitive-motor dual-tasking and various other cognitive measures (Digit Symbol Substitution Test, Cube Rotation, Card Rotation, Rod and Frame Test) before, during and after 15 astronauts completed 6 month missions aboard the ISS. We used linear mixed effect models to analyze performance changes due to entering the microgravity environment, behavioral adaptations aboard the ISS and subsequent recovery from microgravity. We observed declines in mobility and balance from pre- to post-flight, suggesting disruption and/or down weighting of vestibular inputs; these behaviors recovered to baseline levels within 30 days post-flight. We also identified bimanual coordination declines from pre- to post-flight and recovery to baseline levels within 30 days post-flight. There were no changes in dual-task performance during or following spaceflight. Cube rotation response time significantly improved from pre- to post-flight, suggestive of practice effects. There was also a trend for better in-flight cube rotation performance on the ISS when crewmembers had their feet in foot loops on the “floor” throughout the task. This suggests that tactile inputs to the foot sole aided orientation. Overall, these results suggest that sensory reweighting due to the microgravity environment of spaceflight affected sensorimotor performance, while cognitive performance was maintained. A shift from exocentric (gravity) spatial references on Earth toward an egocentric spatial reference may also occur aboard the ISS. Upon return to Earth, microgravity adaptions become maladaptive for certain postural tasks, resulting in transient sensorimotor performance declines that recover within 30 days.

Spaceflight has widespread effects on human performance, including on the ability to dual task. Here, we examine how a spaceflight analog comprising 30 days of head-down-tilt bed rest (HDBR) combined with 0.5% ambient CO2 (HDBR + CO2) influences performance and functional activity of the brain during single and dual tasking of a cognitive and a motor task. The addition of CO2 to HDBR is thought to better mimic the conditions aboard the International Space Station. Participants completed three tasks: (1) COUNT: counting the number of times an oddball stimulus was presented among distractors; (2) TAP: tapping one of two buttons in response to a visual cue; and (3) DUAL: performing both tasks concurrently. Eleven participants (six males) underwent functional MRI (fMRI) while performing these tasks at six time points: twice before HDBR + CO2, twice during HDBR + CO2, and twice after HDBR + CO2. Behavioral measures included reaction time, standard error of reaction time, and tapping accuracy during the TAP and DUAL tasks, and the dual task cost (DTCost) of each of these measures. We also quantified DTCost of fMRI brain activation. In our previous HDBR study of 13 participants (with atmospheric CO2), subjects experienced TAP accuracy improvements during bed rest, whereas TAP accuracy declined while in the current study of HDBR + CO2. In the HDBR + CO2 subjects, we identified a region in the superior frontal gyrus that showed decreased DTCost of brain activation while in HDBR + CO2, and recovered back to baseline levels before the completion of bed rest. Compared to HDBR alone, we found different patterns of brain activation change with HDBR + CO2. HDBR + CO2 subjects had increased DTCost in the middle temporal gyrus whereas HDBR subjects had decreased DTCost in the same area. Five of the HDBR + CO2 subjects developed signs of spaceflight-associated neuro-ocular syndrome (SANS). These subjects exhibited lower baseline dual task activation and higher slopes of change during HDBR + CO2 than subjects with no signs of SANS. Collectively, this pilot study provides insight into the additional and/or interactive effects of CO2 levels during HDBR, and information regarding the impacts of this spaceflight analog environment on the neural correlates of dual tasking.

A lack of efficient operators for wood harvesting machines poses a great challenge. Here, our objective was to evaluate the effect of the behavioural profile on the productive efficiency of forwarder operators. The study was carried out in a Brazilian company, with a sample of 10 operators. A profile evaluation characterized the reference profile, comparing with the profile of the operators studied. The operators were evaluated through their productive efficiency, for 11 months to track learning curves. The results showed that operators must be attentive to details, deadlines, rules, be patient and a moderate initiative taker. The operators were classified into two behavioural profiles, class 1 appropriate to the position and class 2 with some inappropriate points. The productive efficiency of the operators increased during the training, with the profile operators 1 and 2 reaching the targets set by the company in the fifth and seventh month, respectively. The difference in the average productive efficiency between the operators of profile 1 and 2 during the training process was 19%.

Abstract Background Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). Methods The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. Discussion By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. Trial registration This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136.

Astronauts on board the International Space Station (ISS) must adapt to several environmental challenges including microgravity, elevated carbon dioxide (CO2), and isolation while performing highly controlled movements with complex equipment. Head down tilt bed rest (HDBR) is an analog used to study spaceflight factors including body unloading and headward fluid shifts. We recently reported how HDBR with elevated CO2 (HDBR+CO2) affects visuomotor adaptation. Here we expand upon this work and examine the effects of HDBR+CO2 on brain activity during visuomotor adaptation. Eleven participants (34 ± 8 years) completed six functional MRI (fMRI) sessions pre-, during, and post-HDBR+CO2. During fMRI, participants completed a visuomotor adaptation task, divided into baseline, early, late and de-adaptation. Additionally, we compare brain activity between this NASA campaign (30-day HDBR+CO2) and a different campaign with a separate set of participants (60-day HDBR with normal atmospheric CO2 levels, n = 8; 34.25 ± 7.9 years) to characterize the specific effects of CO2. Participants were included by convenience. During early adaptation across the HDBR+CO2 intervention, participants showed decreasing activation in temporal and subcortical brain regions, followed by post- HDBR+CO2 recovery. During late adaptation, participants showed increasing activation in the right fusiform gyrus and right caudate nucleus during HDBR+CO2; this activation normalized to baseline levels after bed rest. There were no correlations between brain changes and adaptation performance changes from pre- to post HDBR+CO2. Also, there were no statistically significant differences between the HDBR+CO2 group and the HDBR controls, suggesting that changes in brain activity were due primarily to bed rest rather than elevated CO2. Five HDBR+CO2 participants presented with optic disc edema, a sign of Spaceflight Associated Neuro-ocular Syndrome (SANS). An exploratory analysis of HDBR+CO2 participants with and without signs of SANS revealed no group differences in brain activity during any phase of the adaptation task. Overall, these findings have implications for spaceflight missions and training, as ISS missions require individuals to adapt to altered sensory inputs over long periods in space. Further, this is the first study to verify the HDBR and elevated CO2 effects on the neural correlates of visuomotor adaptation.

BackgroundWhile it is well-known that deficits in motor performance and brain structural connectivity occur in the course of healthy aging, it is still unclear if and how these changes are related to each other. While some cross-sectional studies suggest that white matter (WM) microstructure is positively associated with motor function in healthy older adults, more evidence is needed. Moreover, longitudinal data is required to estimate whether similar associations can be found between trajectories of change in WM microstructure and motor function. The current study addresses this gap by investigating age-associations and longitudinal changes in WM microstructure and motor function, and the cross-sectional (level-level) and longitudinal (level-change, change-change) association between these two domains.MethodWe used multiple-occasion data (covering 4 years) from a large sample (N = 231) of healthy older adults from the Longitudinal Healthy Aging Brain (LHAB) database. To measure WM microstructure, we used diffusion-weighted imaging data to compute mean FA in three selected WM tracts [forceps minor (FMIN); superior longitudinal fasciculus (SLF); corticospinal tract (CST)]. Motor function was measured via two motor speed tests (grooved pegboard, finger tapping) and one motor strength test (grip force test), separately for the left and the right hand. The statistical analysis was conducted with longitudinal growth curve models in the structural equation modeling framework.ResultsThe results revealed longitudinal decline and negative cross-sectional age-associations for mean WM FA in the FMIN and SLF, and for motor function in all tests, with a higher vulnerability for left than right hand motor performance. Regarding cross-domain associations, we found a significant positive level-level correlation among mean WM FA in the FMIN with motor speed. Mean FA in SLF and CST was not correlated with motor performance measures, and none of the level-change or change-change associations were significant. Overall, our results (a) provide important insights into aging-related changes of fine motor abilities and FA in selected white matter tracts associated with motor control, (b) support previous cross-sectional work showing that neural control of movement in older adults also involves brain structures outside the core motor system and (c) align with the idea that, in healthy aging, compensatory mechanisms may be in place and longer time delays may be needed to reveal level-change or change-change associations.

Astronauts are exposed to microgravity and elevated CO2 levels onboard the International Space Station. Little is known about how microgravity and elevated CO2 combine to affect the brain and sensorimotor performance during and after spaceflight. Here we examined changes in resting-state functional connectivity (FC) and sensorimotor behavior associated with a spaceflight analog environment. Participants underwent 30 days of strict 6o head-down tilt bed rest with elevated ambient CO2 (HDBR+CO2). Resting-state functional magnetic resonance imaging and sensorimotor assessments were collected 13 and 7 days prior to bed rest, on days 7 and 29 of bed rest, and 0, 5, 12, and 13 days following bed rest. We assessed the time course of FC changes from before, during, to after HDBR+CO2. We then compared the observed connectivity changes with those of a HDBR control group that underwent HDBR in standard ambient air. Moreover, we assessed associations between post-HDBR+CO2 FC changes and alterations in sensorimotor performance. HDBR+CO2 was associated with significant changes in functional connectivity between vestibular, visual, somatosensory and motor brain areas. Several of these sensory and motor regions showed post-HDBR+CO2 FC changes that were significantly associated with alterations in sensorimotor performance. We propose that these FC changes reflect multisensory reweighting associated with adaptation to the HDBR+CO2 microgravity analog environment. This knowledge will further improve HDBR as a model of microgravity exposure and contribute to our knowledge of brain and performance changes during and after spaceflight.

Visual and auditory brain network connectivity decline with age, but less is known about age effects on vestibular functional connectivity and its association with behavior. We assessed age differences in the connectivity of the vestibular cortex with other sensory brain regions, both during rest and during vestibular stimulation. We then assessed the relationship between vestibular connectivity and postural stability. A sample of seventeen young and fifteen older adults participated in our study. We assessed the amount of body sway in performing the Romberg balance task, with degraded somatosensory and visual inputs. The results showed no significant difference in balance performance between age groups. However, functional connectivity analyses revealed a main effect of age and condition, suggesting that vestibular connectivity was higher in young adults than older adults, and vestibular connectivity increased from resting state to stimulation trials. Surprisingly, young adults who exhibited higher connectivity during stimulation also had greater body sway. This suggests that young adults who exhibit better balance are those who respond more selectively to vestibular inputs. This correlation is non-significant in older adults, suggesting that the relationship between vestibular functional connectivity and postural stability differs with age.

Spaceflight missions to the International Space Station (ISS) expose astronauts to microgravity, radiation, isolation, and elevated carbon dioxide (CO2), among other factors. Head down tilt bed rest (HDBR) is an Earth-based analog for spaceflight used to study body unloading, fluid shifts, and other factors unrelated to gravitational changes. While in space, astronauts need to use mental rotation strategies to facilitate their adaptation to the ISS environment. Therefore, spatial working memory is essential for crewmember performance. Although the effects of HDBR on spatial working memory have recently been studied, the results are still inconclusive. Here, we expand upon past work and examine the effects of HDBR with elevated CO2 (HDBR + CO2) on brain activation patterns during spatial working memory performance. In addition, we compare brain activation between 30 days of HDBR + CO2 and 70 days of HDBR to test the isolated effect of CO2. Eleven subjects (6 males, 5 females; mean age = 34 ± 8 years) underwent six functional magnetic resonance imaging (fMRI) sessions pre-, during, and post-HDBR + CO2. During the HDBR + CO2 intervention, we observed decreasing activation in the right middle frontal gyrus and left regions of the cerebellum, followed by post-intervention recovery. We detected several correlations between brain and behavioral slopes of change with the HDBR + CO2 intervention. For example, greater increases in activation in frontal, temporal and parietal regions were associated with larger spatial working memory improvements. Comparing the HDBR + CO2 group to data from our previous 70-day HDBR study, we found greater decreases in activation in the right hippocampus and left inferior temporal gyrus for the HDBR + CO2 group over the course of the intervention. Together, these findings increase our understanding of the neural mechanisms of HDBR, elevated levels of CO2 and spaceflight-related changes in spatial working memory performance.

Normal aging is associated with declines in sensorimotor function. Previous studies have linked age-related behavioral declines to decreases in neural differentiation (i.e., dedifferentiation), including decreases in the distinctiveness of neural activation patterns and in the segregation of large-scale neural networks at rest. However, no studies to date have explored the relationship between these two neural measures and whether they explain the same aspects of behavior. To investigate these issues, we collected a battery of sensorimotor behavioral measures in older and younger adults and estimated (a) the distinctiveness of neural representations in sensorimotor cortex and (b) sensorimotor network segregation in the same participants. Consistent with prior findings, sensorimotor representations were less distinct and sensorimotor resting state networks were less segregated in older compared to younger adults. We also found that participants with the most distinct sensorimotor representations exhibited the most segregated sensorimotor networks. However, only sensorimotor network segregation was associated with individual differences in sensorimotor performance, particularly in older adults. These novel findings link network segregation to neural distinctiveness, but also suggest that network segregation may play a larger role in maintaining sensorimotor performance with age.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can facilitate motor learning, but it has not been established how stimulation to other brain regions impacts online and offline motor sequence learning, as well as long-term retention. Here, we completed three experiments comparing the effects of tDCS and sham stimulation to the prefrontal cortex (PFC), M1, and the supplementary motor area complex to understand the contributions of these brain regions to motor sequence learning. In Experiment 1, we found that both left and right PFC tDCS groups displayed a slowing in learning in both reaction time and number of chunks, whereas stimulation over M1 improved both metrics over the course of three sessions. To better understand the sequence learning impairment of left PFC anodal stimulation, we tested a left PFC cathodal tDCS group in Experiment 2. The cathodal group demonstrated learning impairments similar to the left PFC anodal stimulation group. In Experiment 3, a subset of participants from the left PFC, M1, and sham tDCS groups of Experiment 1 returned to complete a single session without tDCS on the same sequences assigned to them 1 year previously. We found that the M1 tDCS group reduced reaction time at a faster rate relative to the sham and left PFC groups, demonstrating faster relearning after a one-year delay. Thus, our findings suggest that, regardless of the polarity of stimulation, tDCS to PFC impairs sequence learning, whereas stimulation to M1 facilitates learning and relearning, especially in terms of chunk formation.

Age-related brain changes likely contribute to mobility impairments, but the specific mechanisms are poorly understood. Current brain measurement approaches (e.g., functional magnetic resonance imaging (fMRI), functional near infrared spectroscopy (fNIRS), PET) are limited by inability to measure activity from the whole brain during walking. The Mind in Motion Study will use cutting edge, mobile, high-density electroencephalography (EEG). This approach relies upon innovative hardware and software to deliver three-dimensional localization of active cortical and subcortical regions with good spatial and temporal resolution during walking. Our overarching objective is to determine age-related changes in the central neural control of walking and correlate these findings with a comprehensive set of mobility outcomes (clinic-based, complex walking, and community mobility measures). Our hypothesis is that age-related walking deficits are explained in part by the Compensation Related Utilization of Neural Circuits Hypothesis (CRUNCH). CRUNCH is a well-supported model that describes the over-recruitment of brain regions exhibited by older adults in comparison to young adults, even at low levels of task complexity. CRUNCH also describes the limited brain reserve resources available with aging. These factors cause older adults to quickly reach a ceiling in brain resources when performing tasks of increasing complexity, leading to poor performance. Two hundred older adults and twenty young adults will undergo extensive baseline neuroimaging and walking assessments. Older adults will subsequently be followed for up to 3 years. Aim 1 will evaluate whether brain activity during actual walking explains mobility decline. Cross sectional and longitudinal designs will be used to study whether poorer walking performance and steeper trajectories of decline are associated with CRUNCH indices. Aim 2 is to harmonize high-density EEG during walking with fNIRS (during actual and imagined walking) and fMRI (during imagined walking). This will allow integration of CRUNCH-related hallmarks of brain activity across neuroimaging modalities, which is expected to lead to more widespread application of study findings. Aim 3 will study central and peripheral mechanisms (e.g., cerebral blood flow, brain regional volumes, and connectivity, sensory function) to explain differences in CRUNCH indices during walking. Research performed in the Mind in Motion Study will comprehensively characterize the aging brain during walking for developing new intervention targets.

Astronauts return to Earth from spaceflight missions with impaired mobility and balance; recovery can last weeks postflight. This is due in large part to the altered vestibular signaling and sensory reweighting that occurs in microgravity. The neural mechanisms of spaceflight-induced vestibular changes are not well understood. Head-down-tilt bed rest (HDBR) is a common spaceflight analog environment that allows for study of body unloading, fluid shifts, and other consequences of spaceflight. Subjects in this context still show vestibular changes despite being in Earth’s gravitational environment, potentially due to sensory reweighting. Previously, we found evidence of sensory reweighting and reduced neural efficiency for vestibular processing in subjects who underwent a 70-day HDBR intervention. Here we extend this work by evaluating the impact of HDBR paired with elevated carbon dioxide (CO2) to mimic International Space Station conditions on vestibular neural processing. Eleven participants (6 males, 34 ± 8 years) completed 30 days of HDBR combined with 0.5% atmospheric CO2 (HDBR + CO2). Participants underwent six functional magnetic resonance imaging (fMRI) sessions pre-, during, and post- HDBR + CO2 while we measured brain activity in response to pneumatic skull taps (a validated method of vestibular stimulation). We also measured mobility and balance performance several times before and after the intervention. We found support for adaptive neural changes within the vestibular system during bed rest that subsequently recovered in several cortical and cerebellar regions. Further, there were multiple brain regions where greater pre- to post- deactivation was associated with reduced pre- to post- balance declines. That is, increased deactivation of certain brain regions associated with better balance post-HDBR + CO2. We also found that, compared to HDBR alone (n = 13 males; 29 ± 3 years) HDBR + CO2 is associated with greater increases in activation of multiple frontal, parietal, and temporal regions during vestibular stimulation. This suggests interactive or additive effects of bed rest and elevated CO2. Finally, we found stronger correlations between pre- to post- HDBR + CO2 brain changes and dependence on the visual system during balance for subjects who developed signs of Spaceflight-Associated Neuro-ocular Syndrome (SANS). Together, these findings have clear implications for understanding the neural mechanisms of bed rest and spaceflight-related changes in vestibular processing, as well as adaptation to altered sensory inputs.

Abstract Background Sensory augmentation has been shown to improve postural stability during real-time balance applications. Limited long-term controlled studies have examined retention of balance improvements in healthy older adults after training with sensory augmentation has ceased. This pilot study aimed to assess the efficacy of long-term balance training with and without sensory augmentation among community-dwelling healthy older adults. Methods Twelve participants (four males, eight females; 75.6 ± 4.9 yrs) were randomly assigned to the experimental group (n = 6) or control group (n = 6). Participants trained in their homes for eight weeks, completing three 45-min exercise sessions per week using smart phone balance trainers that provided written, graphic, and video guidance, and monitored trunk sway. During each session, participants performed six repetitions of six exercises selected from five categories (static standing, compliant surface standing, weight shifting, modified center of gravity, and gait). The experimental group received vibrotactile sensory augmentation for four of the six repetitions per exercise via the smart phone balance trainers, while the control group performed exercises without sensory augmentation. The smart phone balance trainers sent exercise performance data to a physical therapist, who recommended exercises on a weekly basis. Balance performance was assessed using a battery of clinical balance tests (Activity Balance Confidence Scale, Sensory Organization Test, Mini Balance Evaluation Systems Test, Five Times Sit to Stand Test, Four Square Step Test, Functional Reach Test, Gait Speed Test, Timed Up and Go, and Timed Up and Go with Cognitive Task) before training, after four weeks of training, and after eight weeks of training. Results Participants in the experimental group were able to use vibrotactile sensory augmentation independently in their homes. After training, the experimental group had significantly greater improvements in Sensory Organization Test and Mini Balance Evaluation Systems Test scores than the control group. Significant improvement was also observed for Five Times Sit to Stand Test duration within the experimental group, but not in the control group. No significant improvements between the two groups were observed in the remaining clinical outcome measures. Conclusion The findings of this study support the use of sensory augmentation devices by community-dwelling healthy older adults as balance rehabilitation tools, and indicate feasibility of telerehabilitation therapy with reduced input from clinicians.

Abstract The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and axial body unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6° HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n = 12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging was used to quantify distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreases in the post-central gyrus and precuneus correlated negatively with balance changes. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

Long duration head down tilt bed rest (HDBR) has been widely used as a spaceflight analog environment to understand the effects of microgravity on human physiology and performance. Reports have indicated that crewmembers onboard the International Space Station (ISS) experience symptoms of elevated CO2 such as headaches at lower levels of CO2 than levels at which symptoms begin to appear on Earth. This suggests there may be combinatorial effects of elevated CO2 and the other physiological effects of microgravity including headward fluid shifts and body unloading. The purpose of the current study was to investigate these effects by evaluating the impact of 30 days of 6° HDBR and 0.5% CO2 (HDBR + CO2) on mission relevant cognitive and sensorimotor performance. We found a facilitation of processing speed and a decrement in functional mobility for subjects undergoing HDBR + CO2 relative to our previous study of HDBR in ambient air. In addition, nearly half of the participants in this study developed signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), a constellation of ocular structural and functional changes seen in approximately one third of long duration astronauts. This allowed us the unique opportunity to compare the two subgroups. We found that participants who exhibited signs of SANS became more visually dependent and shifted their speed-accuracy tradeoff, such that they were slower but more accurate than those that did not incur ocular changes. These small subgroup findings suggest that SANS may have an impact on mission relevant performance inflight via sensory reweighting.New And NoteworthyWe examined the effects of long duration head down tilt bed rest coupled with elevated CO2 as a spaceflight analog environment on human cognitive and sensorimotor performance. We found enhancements in processing speed and declines in functional mobility. A subset of participants exhibited signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), which affects approximately one in three astronauts. These individuals increased their visual reliance throughout the intervention in comparison to participants who did not show signs of SANS.

Aging is associated with declines in motor and somatosensory function. Some of these motor declines have been linked to age-related reductions in inhibitory function. Here we examined whether tactile surround inhibition also changes with age and whether these changes are associated with those in the motor domain. We tested a group of 56 participants spanning a wide age range (18–76 years old), allowing us to examine when age differences emerge across the lifespan. Participants performed tactile and motor tasks that have previously been linked to inter- and intra-hemispheric inhibition in the somatosensory and motor systems. The results showed that aging is associated with reductions in inhibitory function in both the tactile and motor systems starting around 40 years of age; however, age effects in the two systems were not correlated. The independent effects of age on tactile and motor inhibitory function suggest that distinct mechanisms may underlie age-related reductions in inhibition in the somatosensory and motor systems.

Aging is associated with peripheral and central declines in vestibular processing and postural control. Here we used functional MRI to investigate age differences in neural vestibular representations in response to pneumatic tap stimulation. We also measured the amount of body sway in multiple balance tasks outside of the MRI scanner to assess the relationship between individuals' balance ability and their vestibular neural response. We found a general pattern of activation in canonical vestibular cortex and deactivation in cross modal sensory regions in response to vestibular stimulation. We found that activation amplitude of the vestibular cortex was correlated with age, with younger individuals exhibiting higher activation. Deactivation of visual and somatosensory regions increased with age and was associated with poorer balance. The results demonstrate that brain activations and deactivations in response to vestibular stimuli are correlated with balance, and the pattern of these correlations varies with age. The findings also suggest that older adults exhibit less sensitivity to vestibular stimuli, and may compensate by differentially reweighting visual and somatosensory processes.

Abstract Humans undergo extensive sensorimotor adaptation during spaceflight due to altered vestibular inputs and body unloading. No studies have yet evaluated the effects of spaceflight on human brain structure despite the fact that recently reported optic nerve structural changes are hypothesized to occur due to increased intracranial pressure occurring with microgravity. This is the first report on human brain structural changes with spaceflight. We evaluated retrospective longitudinal T2-weighted MRI scans and balance data from 27 astronauts (thirteen ~2-week shuttle crew members and fourteen ~6-month International Space Station crew members) to determine spaceflight effects on brain structure, and whether any pre to postflight brain changes are associated with balance changes. Data were obtained from the NASA Lifetime Surveillance of Astronaut Health. Brain scans were segmented into gray matter maps and normalized into MNI space using a stepwise approach through subject specific templates. Non-parametric permutation testing was used to analyze pre to postflight volumetric gray matter changes. We found extensive volumetric gray matter decreases, including large areas covering the temporal and frontal poles and around the orbits. This effect was larger in International Space Station versus shuttle crew members in some regions. There were bilateral focal gray matter increases within the medial primary somatosensory and motor cortex; i.e., the cerebral areas where the lower limbs are represented. These intriguing findings are observed in a retrospective data set; future prospective studies should probe the underlying mechanisms and behavioral consequences.