Daily artificial gravity is associated with greater neural efficiency during sensorimotor adaptation.

Altered vestibular signaling and body unloading in microgravity results in sensory reweighting and adaptation. Microgravity effects are well-replicated in head-down tilt bed rest (HDBR). Artificial gravity (AG) is a potential countermeasure to mitigate the effects of microgravity on human physiology and performance. We examined the effectiveness of daily AG for mitigating brain and/or behavioral changes in 60 days of HDBR. One group received AG for 30 minutes daily (AG; n = 16) and a control group spent the same time in HDBR but received no AG (CTRL; n = 8). All participants performed a sensorimotor adaptation task five times during fMRI scanning: twice prior to HDBR, twice during HDBR, and once following HDBR. The AG group showed similar behavioral adaptation effects compared with the CTRLs. We identified decreased brain activation in the AG group from pre to late HDBR in the cerebellum for the task baseline portion and in the thalamus, calcarine, cuneus, premotor cortices, and superior frontal gyrus in the AG group during the early adaptation phase. The two groups also exhibited differential brain-behavior correlations. Together, these results suggest that AG may result in a reduced recruitment of brain activity for basic motor processes and sensorimotor adaptation. These effects may stem from the somatosensory and vestibular stimulation that occur with AG.

Changes in working memory brain activity and task-based connectivity after long-duration spaceflight.

We studied the longitudinal effects of approximately 6 months of spaceflight on brain activity and task-based connectivity during a spatial working memory (SWM) task. We further investigated whether any brain changes correlated with changes in SWM performance from pre- to post-flight. Brain activity was measured using functional magnetic resonance imaging while astronauts (n = 15) performed a SWM task. Data were collected twice pre-flight and 4 times post-flight. No significant effects on SWM performance or brain activity were found due to spaceflight; however, significant pre- to post-flight changes in brain connectivity were evident. Superior occipital gyrus showed pre- to post-flight reductions in task-based connectivity with the rest of the brain. There was also decreased connectivity between the left middle occipital gyrus and the left parahippocampal gyrus, left cerebellum, and left lateral occipital cortex during SWM performance. These results may reflect increased visual network modularity with spaceflight. Further, increased visual and visuomotor connectivity were correlated with improved SWM performance from pre- to post-flight, while decreased visual and visual-frontal cortical connectivity were associated with poorer performance post-flight. These results suggest that while SWM performance remains consistent from pre- to post-flight, underlying changes in connectivity among supporting networks suggest both disruptive and compensatory alterations due to spaceflight.

Artificial gravity during a spaceflight analog alters brain sensory connectivity.

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.

Brain connectivity and behavioral changes in a spaceflight analog environment with elevated CO2.

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.

The effects of a spaceflight analog with elevated CO2 on sensorimotor adaptation.

Aboard the International Space Station (ISS), astronauts must adapt to altered vestibular and somatosensory inputs due to microgravity. Sensorimotor adaptation on Earth is often studied with a task that introduces visuomotor conflict. Retention of the adaptation process, known as savings, can be measured when subjects are exposed to the same adaptive task multiple times. It is unclear how adaptation demands found on the ISS might interfere with the ability to adapt to other sensory conflict at the same time. In the present study, we investigated the impact of 30 days' head-down tilt bed rest combined with elevated carbon dioxide (HDBR + CO2) as a spaceflight analog on sensorimotor adaptation. Eleven subjects used a joystick to move a cursor to targets presented on a computer screen under veridical cursor feedback and 45° rotated feedback. During this NASA campaign, five individuals presented with optic disk edema, a sign of spaceflight-associated neuro-ocular syndrome (SANS). Thus, we also performed post hoc exploratory analyses between subgroups who did and did not show signs of SANS. HDBR + CO2 had some impact on sensorimotor adaptation, with a lack of savings across the whole group. SANS individuals showed larger, more persistent after-effects, suggesting a shift from relying on cognitive to more implicit processing of adaptive behaviors. Overall, these findings suggest that HDBR + CO2 alters the way in which individuals engage in sensorimotor processing. These findings have important implications for missions and mission training, which require individuals to adapt to altered sensory inputs over long periods in space.NEW & NOTEWORTHY This is the first bed rest campaign examining sensorimotor adaptation and savings in response to the combined effect of HDBR + CO2 and to observe signs of spaceflight-associated neuro-ocular syndrome (SANS) in HDBR participants. Our findings suggest that HDBR + CO2 alters the way that individuals engage in sensorimotor processing. Individuals who developed signs of SANS seem to rely more on implicit rather than cognitive processing of adaptive behaviors than subjects who did not present signs of SANS.

Ophthalmic changes in a spaceflight analog are associated with brain functional reorganization.

Following long-duration spaceflight, some astronauts exhibit ophthalmic structural changes referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. The origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. In the current spaceflight analog study, 11 subjects underwent 30 days of strict head down-tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2 ). Using functional magnetic resonance imaging (fMRI), we acquired resting-state fMRI data at 6 time points: before (2), during (2), and after (2) the HDBR+CO2 intervention. Five participants developed optic disc edema during the intervention (SANS subgroup) and 6 did not (NoSANS group). This occurrence allowed us to explore whether development of signs of SANS during the spaceflight analog impacted resting-state functional connectivity during HDBR+CO2 . In light of previous work identifying genetic and biochemical predictors of SANS, we further assessed whether the SANS and NoSANS subgroups exhibited differential patterns of resting-state functional connectivity prior to the HDBR+CO2 intervention. We found that the SANS and NoSANS subgroups exhibited distinct patterns of resting-state functional connectivity changes during HDBR+CO2 within visual and vestibular-related brain networks. The SANS and NoSANS subgroups also exhibited different resting-state functional connectivity prior to HDBR+CO2 within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration. We further present associations between functional connectivity within the identified networks and previously identified genetic and biochemical predictors of SANS. Subgroup differences in resting-state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the spaceflight analog. This finding suggests that SANS impacts not only neuro-ocular structures, but also functional brain organization. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences.

Change of cortical foot activation following 70 days of head-down bed rest.

Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to study some of the effects of microgravity on human physiology, cognition, and sensorimotor functions. Previous studies have reported declines in balance control and functional mobility after spaceflight and HDBR. In this study we investigated how the brain activation for foot movement changed with HDBR. Eighteen healthy men participated in the current HDBR study. They were in a 6° head-down tilt position continuously for 70 days. Functional MRI scans were acquired to estimate brain activation for foot movement before, during, and after HDBR. Another 11 healthy men who did not undergo HDBR participated as control subjects and were scanned at four time points. In the HDBR subjects, the cerebellum, fusiform gyrus, hippocampus, and middle occipital gyrus exhibited HDBR-related increases in activation for foot tapping, whereas no HDBR-associated activation decreases were found. For the control subjects, activation for foot tapping decreased across sessions in a couple of cerebellar regions, whereas no activation increase with session was found. Furthermore, we observed that less HDBR-related decline in functional mobility and balance control was associated with greater pre-to-post HDBR increases in brain activation for foot movement in several cerebral and cerebellar regions. Our results suggest that more neural control is needed for foot movement as a result of HDBR. NEW & NOTEWORTHY Long-duration head-down bed rest serves as a spaceflight analog research environment. We show that brain activity in the cerebellum and visual areas during foot movement increases from pre- to post-bed rest and then shows subsequent recovery. Greater increases were seen for individuals who exhibited less decline in functional mobility and balance control, suggestive of adaptive changes in neural control with long-duration bed rest.

Neural predictors of sensorimotor adaptation rate and savings.

In this study, we investigate whether individual variability in the rate of visuomotor adaptation and multiday savings is associated with differences in regional gray matter volume and resting-state functional connectivity. Thirty-four participants performed a manual adaptation task during two separate test sessions, on average 9 days apart. Functional connectivity strength between sensorimotor, dorsal cingulate, and temporoparietal regions of the brain was found to predict the rate of learning during the early phase of the adaptation task. In contrast, default mode network connectivity strength was found to predict both the rate of learning during the late adaptation phase and savings. As for structural predictors, greater gray matter volume in temporoparietal and occipital regions predicted faster early learning, whereas greater gray matter volume in superior posterior regions of the cerebellum predicted faster late learning. These findings suggest that the offline neural predictors of early adaptation may facilitate the cognitive aspects of sensorimotor adaptation, supported by the involvement of temporoparietal and cingulate networks. The offline neural predictors of late adaptation and savings, including the default mode network and the cerebellum, likely support the storage and modification of newly acquired sensorimotor representations.

Vestibular brain changes within 70 days of head down bed rest.

Head-down-tilt bed rest (HDBR) is frequently utilized as a spaceflight analog research environment to study the effects of axial body unloading and fluid shifts that are associated with spaceflight in the absence of gravitational modifications. HDBR has been shown to result in balance changes, presumably due to sensory reweighting and adaptation processes. Here, we examined whether HDBR results in changes in the neural correlates of vestibular processing. Thirteen men participated in a 70-day HDBR intervention; we measured balance, functional mobility, and functional brain activity in response to vestibular stimulation at 7 time points before, during, and after HDBR. Vestibular stimulation was administered by means of skull taps, resulting in activation of the vestibular cortex and deactivation of the cerebellar, motor, and somatosensory cortices. Activation in the bilateral insular cortex, part of the vestibular network, gradually increased across the course of HDBR, suggesting an upregulation of vestibular inputs in response to the reduced somatosensory inputs experienced during bed rest. Furthermore, greater increase of activation in multiple frontal, parietal, and occipital regions in response to vestibular stimulation during HDBR was associated with greater decrements in balance and mobility from before to after HDBR, suggesting reduced neural efficiency. These findings shed light on neuroplastic changes occurring with conditions of altered sensory inputs, and reveal the potential for central vestibular-somatosensory convergence and reweighting with bed rest.

Effects of a spaceflight analog environment on brain connectivity and behavior.

Sensorimotor functioning is adaptively altered following long-duration spaceflight. The question of whether microgravity affects other central nervous system functions such as brain network organization 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 an established spaceflight analog on resting state brain functional connectivity and its association with behavioral changes in 17 male participants. These bed rest participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. Resting state functional magnetic resonance imaging (rs-fMRI) and behavioral data were obtained at seven time points averaging around: 12 and 8days prior to bed rest; 7, 50, and 70days during bed rest; and 8 and 12days after bed rest. To assess potential confounding effects due to scanning interval or task practice, we also acquired rs-fMRI and behavioral measurements from 14 control participants at four time points. 70days of head-down tilt (HDT) bed rest resulted in significant changes in the functional connectivity of motor, somatosensory, and vestibular areas of the brain. Moreover, several of these network alterations were significantly associated with changes in sensorimotor and spatial working memory performance, which suggests that neuroplasticity mechanisms may facilitate adaptation to the microgravity analog environment. The findings from this study provide novel insights into the underlying neural mechanisms and operational risks of spaceflight analog-related changes in sensorimotor performance.

Study protocol to examine the effects of spaceflight and a spaceflight analog on neurocognitive performance: extent, longevity, and neural bases.

BACKGROUND: 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 spaceflight also affects other central nervous system functions such as cognition is yet largely unknown, but of importance in consideration of the health and performance of crewmembers both in- and post-flight. We are therefore conducting a controlled prospective longitudinal study to investigate the effects of spaceflight on the extent, longevity and neural bases of sensorimotor and cognitive performance changes. Here we present the protocol of our study. METHODS/DESIGN: This study includes three groups (astronauts, bed rest subjects, ground-based control subjects) for which each the design is single group with repeated measures. The effects of spaceflight on the brain will be investigated in astronauts who will be assessed at two time points pre-, at three time points during-, and at four time points following a spaceflight mission of six months. To parse out the effect of microgravity from the overall effects of spaceflight, we investigate the effects of seventy days head-down tilted bed rest. Bed rest subjects will be assessed at two time points before-, two time points during-, and three time points post-bed rest. A third group of ground based controls will be measured at four time points to assess reliability of our measures over time. For all participants and at all time points, except in flight, measures of neurocognitive performance, fine motor control, gait, balance, structural MRI (T1, DTI), task fMRI, and functional connectivity MRI will be obtained. In flight, astronauts will complete some of the tasks that they complete pre- and post flight, including tasks measuring spatial working memory, sensorimotor adaptation, and fine motor performance. Potential changes over time and associations between cognition, motor-behavior, and brain structure and function will be analyzed. DISCUSSION: This study explores how spaceflight induced brain changes impact functional performance. This understanding could aid in the design of targeted countermeasures to mitigate the negative effects of long-duration spaceflight.

Daily Artificial Gravity Partially Mitigates Vestibular Processing Changes Associated with Head-down Tilt Bedrest.

Microgravity alters vestibular signaling and reduces body loading, driving sensory reweighting and adaptation. The unloading effects can be modelled using head down tilt bedrest (HDT). Artificial gravity (AG) has been hypothesized to serve as an integrated countermeasure for the physiological declines associated with HDT and spaceflight. Here, we examined the efficacy of 30 minutes of daily AG to counteract brain and behavior changes that arise from 60 days of HDT. One group of participants received 30 minutes of AG daily (AG; n = 16) while in HDT, and another group served as controls, spending 60 days in HDT bedrest with no AG (CTRL; n = 8). We examined how HDT and AG affect vestibular processing by collecting fMRI scans from participants as they received vestibular stimulation. We collected these data prior to, during (2x), and post HDT. We assessed brain activation initially in 10 regions of interest (ROIs) and then conducted an exploratory whole brain analysis. The AG group showed no changes in brain activation during vestibular stimulation in a cerebellar ROI, whereas the CTRL group showed decreased cerebellar activation specific to the HDT phase. Additionally, those that received AG and showed little pre- to post-bed rest changes in left OP2 activation during HDT had better post-HDT balance performance. Exploratory whole brain analyses identified increased pre- to during-HDT activation in the CTRL group in the right precentral gyrus and the right inferior frontal gyrus specific to HDT, where the AG group maintained pre-HDT activation levels. Together, these results indicate that AG could mitigate brain activation changes in vestibular processing in a manner that is associated with better balance performance after HDT.

Impacts of spaceflight experience on human brain structure.

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.

Cortical thickness of primary motor and vestibular brain regions predicts recovery from fall and balance directly after spaceflight.

Motor adaptations to the microgravity environment during spaceflight allow astronauts to perform adequately in this unique environment. Upon return to Earth, this adaptation is no longer appropriate and can be disruptive for mission critical tasks. Here, we measured if metrics derived from MRI scans collected from astronauts can predict motor performance post-flight. Structural and diffusion MRI scans from 14 astronauts collected before launch, and motor measures (balance performance, speed of recovery from fall, and tandem walk step accuracy) collected pre-flight and post-flight were analyzed. Regional measures of gray matter volume (motor cortex, paracentral lobule, cerebellum), myelin density (motor cortex, paracentral lobule, corticospinal tract), and white matter microstructure (corticospinal tract) were derived as a-priori predictors. Additional whole-brain analyses of cortical thickness, cerebellar gray matter, and cortical myelin were also tested for associations with post-flight and pre-to-post-flight motor performance. The pre-selected regional measures were not significantly associated with motor behavior. However, whole-brain analyses showed that paracentral and precentral gyri thickness significantly predicted recovery from fall post-spaceflight. Thickness of vestibular and sensorimotor regions, including the posterior insula and the superior temporal gyrus, predicted balance performance post-flight and pre-to-post-flight decrements. Greater cortical thickness pre-flight predicted better performance post-flight. Regional thickness of somatosensory, motor, and vestibular brain regions has some predictive value for post-flight motor performance in astronauts, which may be used for the identification of training and countermeasure strategies targeted for maintaining operational task performance.

The Effects of 30 Minutes of Artificial Gravity on Cognitive and Sensorimotor Performance in a Spaceflight Analog Environment.

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.

Longitudinal MRI-visible perivascular space (PVS) changes with long-duration spaceflight.

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 T1-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 < 0.001). In addition, we found high reliability for four of five PVS metrics across the two pre-flight time points and across the four control time points (ICC(3,k) > 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 T1-weighted MRI scans, and that spaceflight is associated with PVS changes. Specifically, prior spaceflight experience may be an important factor in determining PVS characteristics.

Head-Down-Tilt Bed Rest With Elevated CO2: Effects of a Pilot Spaceflight Analog on Neural Function and Performance During a Cognitive-Motor Dual Task.

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.

Effects of Spaceflight Stressors on Brain Volume, Microstructure, and Intracranial Fluid Distribution.

Astronauts are exposed to elevated CO2 levels onboard the International Space Station. Here, we investigated structural brain changes in 11 participants following 30-days of head-down tilt bed rest (HDBR) combined with 0.5% ambient CO2 (HDBR + CO2) as a spaceflight analog. We contrasted brain changes observed in the HDBR + CO2 group with those of a previous HDBR sample not exposed to elevated CO2. Both groups exhibited a global upward shift of the brain and concomitant intracranial free water (FW) redistribution. Greater gray matter changes were seen in the HDBR + CO2 group in some regions. The HDBR + CO2 group showed significantly greater FW decrements in the posterior cerebellum and the cerebrum than the HDBR group. In comparison to the HDBR group, the HDBR + CO2 group exhibited greater diffusivity increases. In half of the participants, the HDBR + CO2 intervention resulted in signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), a constellation of ocular structural and functional changes seen in astronauts. We therefore conducted an exploratory comparison compared between subjects that did and did not develop SANS and found asymmetric lateral ventricle enlargement in the SANS group. These results enhance our understanding of the underlying mechanisms of spaceflight-induced brain changes, which is critical for promoting astronaut health and performance.

The Effects of Long Duration Spaceflight on Sensorimotor Control and Cognition.

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.

Visuomotor Adaptation Brain Changes During a Spaceflight Analog With Elevated Carbon Dioxide (CO2): A Pilot Study.

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.