Daily artificial gravity partially mitigates vestibular processing changes associated with head-down tilt bedrest

Spaceflight causes transient balance and mobility deficits due to altered vestibular signaling and multisensory reweighting in microgravity. Vestibular inputs are downweighted in microgravity because signals are unreliable without gravity. Upon return to Earth, these adaptive responses become maladaptive, hindering locomotion and balance. Studies show vestibular neural changes during and after spaceflight, such as reduced alpha power in vestibular, motor, and cerebellar regions and decreased vestibular resting-state network connectivity. Previous research, using fMRI during vestibular stimulation pre- and post-flight, revealed widespread reductions in brain deactivation across sensorimotor, frontal, temporal, and occipital regions post-flight, suggesting upweighting of somatosensory and visual processing. A brain-behavior correlation was observed between pre- to post-flight activation changes in visual and multisensory integration regions and balance performance. Head-down tilt bedrest (HDT) simulates microgravity's physiological effects, including headward fluid shifts, axial body unloading, and sensory reweighting. While HDT doesn't directly affect vestibular inputs, it is thought to initiate sensory reweighting due to proprioceptive input from limbs. During HDT, higher-frequency linear accelerations associated with locomotion are absent, and somatosensory inputs to the foot sole are removed. Vestibular processing is altered, with vestibular cues upweighted. Performance of vestibular and multisensory-dependent behaviors, such as mobility and balance, decreases after HDT. Previous studies have demonstrated that HDT affects the neural correlates of vestibular processing, and further that the combination of HDT and elevated CO2 affects vestibular processing. The ideal countermeasure for post-flight physiological and functional changes would be integrated to target multiple systems simultaneously. Artificial gravity (AG), applied along the body's long axis via centrifugation, has been proposed as such a countermeasure. Previous research using different AG exposure protocols during HDT has shown that AG can mitigate orthostatic intolerance and balance deficits, improve cognitive performance during centrifugation, and increase neural efficiency during sensorimotor adaptation tasks. However, some studies found no mitigation effect of AG on balance. This study aims to determine if AG applied along the long axis of the body mitigates vestibular processing changes during HDT and if individual differences in brain changes correlate with decreases in balance and mobility.

Extensive research demonstrates the detrimental effects of microgravity on the vestibular system and sensorimotor function. Studies have shown altered vestibular signaling and multisensory reweighting in astronauts after spaceflight, leading to balance and mobility impairments. Neuroimaging studies have identified specific brain regions involved in these changes, including the vestibular cortex, cerebellum, and sensorimotor areas. Head-down tilt bed rest (HDT) has emerged as a valuable ground-based model for simulating the physiological effects of microgravity, allowing researchers to study these effects without the risks and costs of spaceflight. Numerous studies using HDT have confirmed the vestibular and sensorimotor impairments observed in astronauts, along with their neural correlates. These studies provide a strong foundation for understanding the mechanisms underlying these changes and for developing effective countermeasures. The investigation of artificial gravity (AG) as a potential countermeasure has yielded mixed results, with some studies reporting positive effects on balance and cognitive function while others have not observed significant benefits. These inconsistencies underscore the need for further investigation into optimal AG protocols and their effects on various aspects of sensorimotor function and neural plasticity.

Twenty-four participants (8 female; mean age 33.3 ± 9.17 years) underwent a 60-day head-down tilt bedrest (HDT) study. Participants were screened for AG tolerability and randomly assigned to one of three groups: two artificial gravity (AG) groups (30 min daily AG, one continuous bout vs. six 5-min bouts), and a control group (no AG). Vestibular evoked myogenic potentials (VEMPs) were measured using electromyography (EMG). Functional magnetic resonance imaging (fMRI) data were collected during vestibular stimulation (cheekbone taps) at four time points: 7 days pre-HDT (BDC-7), days 29 and 58 of HDT (HDT29, HDT58), and 10 days post-HDT (R+10). Twelve regions of interest (ROIs), previously implicated in vestibular processing, were analyzed. Whole-brain analyses were also conducted to explore additional brain regions affected by HDT and AG. Functional mobility (FMT) and balance (SOT-5, SOT-5M) tests were performed at BDC-1 and R+0. fMRI data were preprocessed using SPM12, ANTs, and FSL tools, correcting for slice timing, realignment, and motion artifacts. Cerebellar data were preprocessed using CERES and SUIT. Statistical analyses included mixed-effects models for behavioral data and longitudinal models for fMRI data using the Sandwich Estimator Toolbox (SwE) for SPM12. Brain-behavior correlations examined associations between brain activation changes and changes in mobility and balance performance.

Analysis of fMRI data revealed a significant group-by-time interaction in the right cerebellar lobule VI, with the AG group maintaining stable activation levels throughout HDT while the control group showed decreased activation. Three group main effects were identified in specific ROIs. A significant correlation was found in the AG group between changes in left OP2 activation (a region associated with the vestibular cortex) and SOT-5 balance performance from pre- to post-HDT; participants maintaining pre-HDT activation levels showed the least balance decline. Whole-brain analysis identified increased activation in the right precentral gyrus and right inferior frontal gyrus in the control group during HDT, while the AG group maintained pre-HDT levels. These findings suggest that AG mitigated the HDT-induced changes in brain activation associated with balance and mobility.

This study demonstrates the potential of artificial gravity (AG) as an integrated countermeasure to mitigate the negative effects of head-down tilt bedrest (HDT) on vestibular processing and balance. The findings support the hypothesis that AG can partially counteract the neural adaptations associated with HDT, potentially through enhanced sensory stimulation and preservation of vestibular system function. The observed brain-behavior correlations further highlight the functional relevance of these neural changes, with better balance performance associated with maintaining pre-HDT levels of brain activation in vestibular-related regions. These results are consistent with previous research on the effects of spaceflight on vestibular function and support the continued exploration of AG as a countermeasure for spaceflight-induced impairments. The results suggest that AG may be a promising countermeasure for preventing or mitigating the decline in balance and mobility experienced by astronauts during and after long-duration space missions. This has implications for the design of future space missions, the safety of astronauts and the feasibility of long-duration space exploration.

This study provides evidence supporting the potential of daily artificial gravity (AG) as a countermeasure for the vestibular processing changes associated with prolonged periods of unloading, such as those experienced during spaceflight. The mitigation of these changes by AG was linked to improved balance performance. Future research should investigate optimal AG protocols, focusing on individual differences in response and the duration of AG exposure needed for maximal benefit. Larger, longer-duration studies are needed to confirm these findings and to determine the long-term effectiveness of AG as a countermeasure for spaceflight-induced impairments.

This study has several limitations. Despite randomization, group differences existed in some ROIs before HDT, possibly due to chance. The sample size was relatively small, limiting statistical power. The 60-day HDT period is shorter than typical ISS missions, potentially resulting in less pronounced dysfunction. AG may require individualized dosing, with rotational speed and duration tailored to each individual's response. The level of gz at the vestibular organ is less than that at CoM. Improved methods of centrifugation might enhance effectiveness.