Dry immersion rapidly disturbs iron metabolism in men and women: results from the VIVALDI studies.

Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in men. However, its impact on women remains unclear. This study aims to compare iron metabolism alterations in both sexes exposed to 5 days of dry immersion. Our findings demonstrate that women, similarly to men, experience increased systemic iron availability and elevated serum hepcidin levels, indicative of iron misdistribution after short-term exposure to simulated microgravity.

How are cell and tissue structure and function influenced by gravity and what are the gravity perception mechanisms?

Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses. Despite the progress made so far, for future space exploration programs it is necessary to increase our knowledge on the mechanotransduction processes as well as on the molecular mechanisms underlying microgravity-induced cell and tissue alterations. This white paper reports the suggestions and recommendations of the SciSpacE Science Community for the elaboration of the section of the European Space Agency roadmap "Biology in Space and Analogue Environments" focusing on "How are cells and tissues influenced by gravity and what are the gravity perception mechanisms?" The knowledge gaps that prevent the Science Community from fully answering this question and the activities proposed to fill them are discussed.

Evidence of Vestibular and Balance Dysfunction in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

OBJECTIVES: Given the expected rise in dementia prevalence, early diagnosis is vital. As a growing body of literature has identified a potential association between vestibular function and cognition, vestibular assessment may aid in early screening. The aim of the study was to better comprehend the proposed association between vestibular function and Alzheimer's disease (AD) by comparing vestibular parameters (vestibular function testing and clinical balance measures) between a group with mild cognitive impairment (MCI), AD, and healthy controls with age-normal cognition. DESIGN: Cross-sectional analysis of the GECkO study, an ongoing prospective single-center longitudinal cohort study. This study included 100 older adults (55 to 84 years). A total of 33 participants with MCI, 17 participants with AD, and 50 participants of age, sex, and hearing-matched healthy controls were included. RESULTS: Participants with AD demonstrated a delayed latency of the p13 component measured by cervical vestibular-evoked myogenic potentials (cVEMP) compared with healthy controls and participants with MCI. Other measures including n23 latency, presence of intact responses, rectified amplitude, mean rectified voltage (measured by cVEMP) and lateral vestibulo-ocular reflex gain (measured by video Head Impulse Test [vHIT]) did not differ between groups. The Timed Up and Go (TUG), Performance-Oriented Mobility Assessment-Balance subscale (POMA-B), and Functional Gait Assessment (FGA) differed significantly between the three groups. Here, more cognitively impaired groups were associated with worse clinical balance scores. CONCLUSIONS: Vestibular and balance deficits were more prevalent in groups with increasing cognitive decline. Regarding vestibular function testing, p13 latency as measured by cVEMP was delayed in participants with AD. Other cVEMP or vHIT measures did not differ between groups. All three clinical balance assessments (TUG, POMA-B, and FGA) resulted in worse scores along the AD continuum. Future research integrating vestibular parameters that add value (including otolith function testing, balance, and spatial navigation) is recommended to validate the association between vestibular function and cognition while avoiding redundant testing.

Is vestibular function related to human hippocampal volume?

BACKGROUND: Recent studies implicate the effect of vestibular loss on cognitive decline, including hippocampal volume loss. As hippocampal atrophy is an important biomarker of Alzheimer's disease, exploring vestibular dysfunction as a risk factor for dementia and its role in hippocampal atrophy is of interest. OBJECTIVE: To replicate previous literature on whole-brain and hippocampal volume in semicircular canal dysfunction (bilateral vestibulopathy; BV) and explore the association between otolith function and hippocampal volume. METHODS: Hippocampal and whole-brain MRI volumes were compared in adults aged between 55 and 83 years. Participants with BV (n = 16) were compared to controls individually matched on age, sex, and hearing status (n = 16). Otolith influence on hippocampal volume in preserved semicircular canal function was evaluated (n = 34). RESULTS: Whole-brain and targeted hippocampal approaches using volumetric and surface-based measures yielded no significant differences when comparing BV to controls. Binary support vector machines were unable to classify inner ear health status above chance level. Otolith parameters were not associated with hippocampal volume in preserved semicircular canal function. CONCLUSIONS: No significant differences in whole-brain or hippocampal volume were found when comparing BV participants with healthy controls. Saccular parameters in subjects with preserved semicircular canal function were not associated with hippocampal volume changes.

How do gravity alterations affect animal and human systems at a cellular/tissue level?

The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: "How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?" This is one of the five major scientific issues of the ESA roadmap "Biology in Space and Analogue Environments". Despite the many studies conducted so far on spaceflight adaptation mechanisms and related pathophysiological alterations observed in astronauts, we are not yet able to elaborate a synthetic integrated model of the many changes occurring at different system and functional levels. Consequently, it is difficult to develop credible models for predicting long-term consequences of human adaptation to the space environment, as well as to implement medical support plans for long-term missions and a strategy for preventing the possible health risks due to prolonged exposure to spaceflight beyond the low Earth orbit (LEO). The research activities suggested by the scientific community have the aim to overcome these problems by striving to connect biological and physiological aspects in a more holistic view of space adaptation effects.

Comprehensive assessment of physiological responses in women during the ESA dry immersion VIVALDI microgravity simulation.

Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974). Here we show that dry immersion rapidly induces a sedentarily-like metabolism shift mimicking the beginning of a metabolic syndrome with a drop in glucose tolerance, an increase in the atherogenic index of plasma, and an impaired lipid profile. Bone remodeling markers suggest a decreased bone formation coupled with an increased bone resorption. Fluid shifts and muscular unloading participate to a marked cardiovascular and sensorimotor deconditioning with decreased orthostatic tolerance, aerobic capacity, and postural balance. Collected datasets provide a comprehensive multi-systemic assessment of dry immersion effects in women and pave the way for future sex-based evaluations of countermeasures.

Evaluation of hearing levels and vestibular function and the impact on cognitive performance in (pre)-symptomatic patients with DFNA9: protocol for a prospective longitudinal study (Rosetta study).

INTRODUCTION: Untreated hearing loss is the largest potentially modifiable risk factor for dementia. Additionally, vestibular dysfunction has been put forward as a potential risk factor for accelerated cognitive decline. Patients with Deafness Autosomal Dominant 9 (DFNA9) present with progressive sensorineural hearing loss and bilateral vestibulopathy and show significantly worse results in cognitive performance compared with a cognitively healthy control group. This highlights the need for adequate treatment to prevent further cognitive decline. This study aims to determine how hearing and vestibular function evolve in (pre-)symptomatic carriers of the p.Pro51Ser mutation in the COCH gene and how this impacts their cognitive performance and health-related quality of life. METHODS AND ANALYSIS: A prospective, longitudinal evaluation of hearing, vestibular function and cognitive performance will be acquired at baseline, 1-year and 2-year follow-up. A total of 40 patients with DFNA9 will be included in the study. The study will be a single-centre study performed at the ORL department at the Antwerp University Hospital (UZA), Belgium. The control group will encompass cognitively healthy subjects, already recruited through the GECkO study. The primary outcome measure will be the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for the Hearing-Impaired total score. Secondary outcome measures include Cortical Auditory-Evoked Potentials, vestibular assessments and health-related quality of life questionnaires. The expected outcomes will aid in the development of gene therapy by providing insight in the optimal time window for the application of gene therapy for the inner ear. ETHICS AND DISSEMINATION: The ethical committee of UZA approved the study protocol on 19 December 2022 (protocol number B3002022000170). All participants have to give written initial informed consent in accordance with the Declaration of Helsinki. Results will be disseminated to the public through conference presentations, lectures and peer-reviewed scientific publications.

3D Bioprinting in Microgravity: Opportunities, Challenges, and Possible Applications in Space.

3D bioprinting has developed tremendously in the last couple of years and enables the fabrication of simple, as well as complex, tissue models. The international space agencies have recognized the unique opportunities of these technologies for manufacturing cell and tissue models for basic research in space, in particular for investigating the effects of microgravity and cosmic radiation on different types of human tissues. In addition, bioprinting is capable of producing clinically applicable tissue grafts, and its implementation in space therefore can support the autonomous medical treatment options for astronauts in future long term and far-distant space missions. The article discusses opportunities but also challenges of operating different types of bioprinters under space conditions, mainly in microgravity. While some process steps, most of which involving the handling of liquids, are challenging under microgravity, this environment can help overcome problems such as cell sedimentation in low viscous bioinks. Hopefully, this publication will motivate more researchers to engage in the topic, with publicly available bioprinting opportunities becoming available at the International Space Station (ISS) in the imminent future.

Neuroplasticity in F16 fighter jet pilots.

Exposure to altered g-levels causes unusual sensorimotor demands that must be dealt with by the brain. This study aimed to investigate whether fighter pilots, who are exposed to frequent g-level transitions and high g-levels, show differential functional characteristics compared to matched controls, indicative of neuroplasticity. We acquired resting-state functional magnetic resonance imaging data to assess brain functional connectivity (FC) changes with increasing flight experience in pilots and to assess differences in FC between pilots and controls. We performed whole-brain exploratory and region-of-interest (ROI) analyses, with the right parietal operculum 2 (OP2) and the right angular gyrus (AG) as ROIs. Our results show positive correlations with flight experience in the left inferior and right middle frontal gyri, and in the right temporal pole. Negative correlations were observed in primary sensorimotor regions. We found decreased whole-brain functional connectivity of the left inferior frontal gyrus in fighter pilots compared to controls and this cluster showed decreased functional connectivity with the medial superior frontal gyrus. Functional connectivity increased between the right parietal operculum 2 and the left visual cortex, and between the right and left angular gyrus in pilots compared to controls. These findings suggest altered motor, vestibular, and multisensory processing in the brains of fighter pilots, possibly reflecting coping strategies to altered sensorimotor demands during flight. Altered functional connectivity in frontal areas may reflect adaptive cognitive strategies to cope with challenging conditions during flight. These findings provide novel insights into brain functional characteristics of fighter pilots, which may be of interest to humans traveling to space.

Prolonged microgravity induces reversible and persistent changes on human cerebral connectivity.

The prospect of continued manned space missions warrants an in-depth understanding of how prolonged microgravity affects the human brain. Functional magnetic resonance imaging (fMRI) can pinpoint changes reflecting adaptive neuroplasticity across time. We acquired resting-state fMRI data of cosmonauts before, shortly after, and eight months after spaceflight as a follow-up to assess global connectivity changes over time. Our results show persisting connectivity decreases in posterior cingulate cortex and thalamus and persisting increases in the right angular gyrus. Connectivity in the bilateral insular cortex decreased after spaceflight, which reversed at follow-up. No significant connectivity changes across eight months were found in a matched control group. Overall, we show that altered gravitational environments influence functional connectivity longitudinally in multimodal brain hubs, reflecting adaptations to unfamiliar and conflicting sensory input in microgravity. These results provide insights into brain functional modifications occurring during spaceflight, and their further development when back on Earth.

Accelerated Cognitive Decline Associated With Hearing Loss and Bilateral Vestibulopathy: Insights From a Prospective Cross-Sectional Study Using the Repeatable Battery for the Assessment of Neuropsychological Status Adjusted for the Hearing Impaired in the DFNA9 Population.

BACKGROUND: DeaFNess Autosomal dominant 9 (DFNA9) is a hereditary disorder known to affect both hearing and vestibular function in its carriers. Its phenotype is characterized by progressive sensorineural hearing loss (SNHL) and vestibular dysfunction evolving towards bilateral vestibulopathy (BV) by the 3rd to 5th life decade. Recent studies have identified the impact of hearing loss and vestibular dysfunction on cognitive functioning. OBJECTIVE: The main objective of this study was to investigate how the cognitive functioning of carriers of the p.Pro51Ser variant in the COCH gene is affected by the disease and compare these results with a matched healthy control group. STUDY DESIGN: Forty-six carriers of the pathogenic p.Pro51Ser variant in the COCH gene were included in this study, of which 38 met the Bárány Society criteria and were thus diagnosed with BV. All subjects were between the age of 22 and 72 years old. Each control was individually matched based on age, gender, and education level. A cognitive, vestibular, and hearing assessment was performed in all subjects. All participants completed the Repeatable Battery for the Assessment of Neuropsychological Status, adjusted for the Hearing Impaired (RBANS-H), a cognitive test battery that includes subtests probing Immediate and Delayed Memory, Visuospatial/Constructional, Language, and Attention. RESULTS: Overall, the DFNA9 patients demonstrated significantly lower scores on the Immediate Memory subscale and lower Total Scale scores than their healthy matched controls. The total sample was divided into two groups: age <55 years old and age ≥55 years old. The DFNA9 group aged ≥55 years old obtained significantly lower scores on the Attention subscale and lower Total Scale scores than their matched controls. Cognition of DFNA9 patients aged <55 years old no longer differed significantly from their matched controls. CONCLUSION: This cross-sectional study found that DFNA9 patients demonstrated cognitive deficits in comparison with their healthy matched controls. The DFNA9 group aged ≥ 55 years old obtained significantly lower scores on the Total Scale and Attention subscale. This finding; however, was not observed for the age group younger than 55 years old. Further research is needed on the individual trajectory of SNHL and vestibular function, and how hearing rehabilitation affects cognitive functioning.

Associations of Bilateral Vestibulopathy With Cognition in Older Adults Matched With Healthy Controls for Hearing Status.

Importance: Recent literature suggests there may be a significant effect of the vestibular system on cognition and visuospatial processing. Given the increasing prevalence of dementia and individuals at risk for it, exploring possible modifiable risk factors, including vestibular dysfunction, is vital. Objectives: To explore the association of bilateral vestibulopathy (BV) with cognitive function in older adults, taking hearing status into account, and to explore multiple vestibular characteristics and their potential associations with cognition in patients with BV. Design, Setting, and Participants: This cross-sectional study assessed older adults (age 55-84 years) with diagnosed BV from a single center using baseline measurements from the Gehoor, Evenwicht en Cognitie (GECKO) study, an ongoing prospective longitudinal cohort study. Each participant was individually matched with a healthy control based on age, sex, and hearing performance. Data were analyzed in January 2022. Main Outcomes and Measures: The primary outcome measure was cognition, measured by the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing-Impaired Individuals (RBANS-H). Results: A total of 68 patients were assessed, including 34 patients with BV (mean [SD] age, 63.3 [6.0] years; 18 [53%] men) matched with 34 control individuals without BV. Overall, participants with BV had a clinically meaningful lower score on the RBANS-H total scale compared with those without BV (mean [SD] score, 98.62 [12.70] vs 105.91 [11.03]). This decline was most pronounced in the subdomains of immediate memory (mean [SD] score, 107.74 [10.66] vs 112.26 [10.66]), visuospatial cognition (mean [SD] score, 90.06 [13.34] vs 100.47 [13.91]), and attention (mean [SD] score, 94.79 [16.39] vs 102.06 [12.97]). There were no differences in language or delayed memory subdomains. Within the BV population, 1 vestibular parameter (the Performance-Oriented Mobility Assessment, in particular the balance subscale) was associated with lower cognitive scores (r32 = 0.51; 95% CI, 0.20 to 0.72; η2 = 0.26). Other vestibular parameters, including measurements of the peripheral vestibular end organ and questionnaires, showed no association. Conclusions and Relevance: These findings suggest there was an association between vestibular loss and cognitive impairment. Further research on the causal mechanisms underlying this association and the possible impact of vestibular rehabilitation on cognition is needed.

The effect of prolonged spaceflight on cerebrospinal fluid and perivascular spaces of astronauts and cosmonauts.

Long-duration spaceflight induces changes to the brain and cerebrospinal fluid compartments and visual acuity problems known as spaceflight-associated neuro-ocular syndrome (SANS). The clinical relevance of these changes and whether they equally affect crews of different space agencies remain unknown. We used MRI to analyze the alterations occurring in the perivascular spaces (PVS) in NASA and European Space Agency astronauts and Roscosmos cosmonauts after a 6-mo spaceflight on the International Space Station (ISS). We found increased volume of basal ganglia PVS and white matter PVS (WM-PVS) after spaceflight, which was more prominent in the NASA crew than the Roscosmos crew. Moreover, both crews demonstrated a similar degree of lateral ventricle enlargement and decreased subarachnoid space at the vertex, which was correlated with WM-PVS enlargement. As all crews experienced the same environment aboard the ISS, the differences in WM-PVS enlargement may have been due to, among other factors, differences in the use of countermeasures and high-resistive exercise regimes, which can influence brain fluid redistribution. Moreover, NASA astronauts who developed SANS had greater pre- and postflight WM-PVS volumes than those unaffected. These results provide evidence for a potential link between WM-PVS fluid and SANS.

Brain Connectometry Changes in Space Travelers After Long-Duration Spaceflight.

Humans undergo extreme physiological changes when subjected to long periods of weightlessness, and as we continue to become a space-faring species, it is imperative that we fully understand the physiological changes that occur in the human body, including the brain. In this study, we present findings of brain structural changes associated with long-duration spaceflight based on diffusion magnetic resonance imaging (dMRI) data. Twelve cosmonauts who spent an average of six months aboard the International Space Station (ISS) were scanned in an MRI scanner pre-flight, ten days after flight, and at a follow-up time point seven months after flight. We performed differential tractography, a technique that confines white matter fiber tracking to voxels showing microstructural changes. We found significant microstructural changes in several large white matter tracts, such as the corpus callosum, arcuate fasciculus, corticospinal, corticostriatal, and cerebellar tracts. This is the first paper to use fiber tractography to investigate which specific tracts exhibit structural changes after long-duration spaceflight and may direct future research to investigate brain functional and behavioral changes associated with these white matter pathways.

Driving ability in patients with dizziness: a systematic review.

PURPOSE: The aim of this systematic review was to identify and evaluate studies dealing with driving performance of dizzy patients or patients with a vestibular disorder. METHODS: A systematic review was performed according to the preferred reporting items for systematic reviews and meta-analysis guidelines. (1) PubMed, Embase, and Cochrane library. (2) Study selection: articles about driving ability and reported driving difficulties in patients with dizziness, or a diagnosed vestibular disorder, were included. (3) Data extraction was performed by two independent authors using predefined data fields: patient's characteristics, diagnostic criteria, sample size, and type of evaluation of driving ability and outcome of the study. RESULTS: Eight out of 705 articles matched the inclusion criteria but varied widely regarding the study population, study design, and outcome measures. The majority of studies reported a negative impact of dizziness and/or vestibular disorders on self-reported driving ability and car accidents. Yet several studies could not identify any impairment of driving ability. CONCLUSIONS: Driving ability was negatively affected by dizziness or a vestibular disorder in the majority of included studies with low risk of bias. This systematic review revealed a significant heterogeneity in studies reporting driving performance and contradictory results. We were, therefore, unable to identify a causal relationship between dizziness and driving ability. There is a need for prospective studies in populations with different vestibular disorders using subjective and objective outcome measures that have been validated to evaluate driving performance.

Cortical Auditory Evoked Potentials in Cognitive Impairment and Their Relevance to Hearing Loss: A Systematic Review Highlighting the Evidence Gap.

Background: Alzheimer's disease (AD) is the most prevalent cause of dementia which affects a growing number of people worldwide. Early identification of people at risk to develop AD should be prioritized. Hearing loss is considered an independent potentially modifiable risk factor for accelerated cognitive decline and dementia in older adults. The main outcome of interest of this review is the alteration of Cortical Auditory Evoked Potential (CAEP) morphology in an AD or mild cognitive impairment (MCI) population with and without hearing loss. Methods: Two investigators independently and systematically searched publications regarding auditory processing on a cortical level in people with cognitive impairment (MCI or AD) with and without hearing loss. Only articles which mentioned at least one auditory elicited event-related potential (ERP) component and that were written in English or Dutch were included. Animal studies were excluded. No restrictions were imposed regarding publication date. The reference list of potential sources were screened for additional articles. Results: This systematic review found no eligible articles that met all inclusion criteria. Therefore, no results were included, resulting in an empty systematic review. Conclusion: In general, dysfunction - being either from cognitive or auditory origin - reduces CAEP amplitudes and prolongs latencies. Therefore, CAEPs may be a prognostic indicator in the early stages of cognitive decline. However, it remains unclear which CAEP component alteration is due to cognitive impairment, and which is due to hearing loss (or even both). In addition, vestibular dysfunction - associated with hearing loss, cognitive impairment and AD - may also alter CAEP responses. Further CAEP studies are warranted, integrating cognitive, hearing, and vestibular evaluations.

Vestibular Function in Older Adults With Cognitive Impairment: A Systematic Review.

IMPORTANCE: Given the rising prevalence of patients with dementia and those at risk for it, early identification is prioritized. As vestibular dysfunction is associated with Alzheimer's disease (AD) and may contribute to its onset, vestibular assessment may yield an opportunity in early dementia screening. OBJECTIVE: This systematic review structures and compares the different raw outcome measures used to assess vestibular function while comparing older adults with preserved cognition to individuals with cognitive impairment, either suffering from mild cognitive impairment (MCI) or AD. DESIGN: Two investigators independently and systematically searched publications performing objectively measured vestibular testing in a patient population consisting of either MCI or AD, compared with a control group of older adults with preserved cognition. No limitations regarding language or publication date were applied. References of the retrieved articles were hand searched for relevant articles. RESULTS: Seven articles were included for analysis. A total of 235 older adults with impaired cognition (150 AD, 85 MCI) were compared with a control group of 481 older adults with preserved cognition. Evaluation of the peripheral vestibular function included video head impulse test (vHIT), videonystagmography (VNG), electronystagmography (ENG) including bithermal caloric irrigation and vestibular evoked myogenic potentials (VEMP). The VEMP test, assessing otolith function and the elicited vestibulocollic reflex (VCR), was able to differentiate subjects with AD and its prodromal stage from healthy controls, with p13 latency (p < 0.05) and amplitude (p < 0.05) having the most discriminating power.No correlation between cognitive decline and vestibulo-ocular reflex measurements in different frequency ranges of the semicircular canals (using vHIT, rotatory chair testing, and caloric irrigation) was found. Because of the limited number of available studies and the large heterogeneity in outcome measures, these results have to be interpreted with caution. CONCLUSIONS: Measurements of the VCR, as evoked by the VEMP test, discriminate between patients with cognitive impairment (MCI and AD) and older adults with preserved cognition, whereas measurements of the vestibulo-ocular reflex do not. More studies are needed to further elaborate on these findings.

'White Mars' - nearly two decades of biomedical research at the Antarctic Concordia station.

NEW FINDINGS: What is the topic of this review? Biomedical research at the Antarctic Concordia Station. What advances does it highlight? Overview of findings in psychology, neuroscience, sleep, cardiovascular physiology and immune system, relevant in isolated, confined and extreme environments and spaceflight. ABSTRACT: Extended stays in isolated, confined and extreme (ICE) environments like Antarctica are associated with a whole set of psychological and physiological challenges for the crew. As such, winter-over stays at Antarctica provide an important opportunity to acquire knowledge into the physiological and psychological changes that ICE environments inevitably bring. The European Space Agency (ESA) is particularly interested in conducting research in such an environment, as it is a unique opportunity to translate these results to space crews experiencing very similar issues. In the past two decades, the ESA has supported a total of 36 biomedical research projects at the Concordia station in collaboration with the French and Italian polar institutes. More specifically, studies in the areas of psychology, neuroscience, sleep physiology, cardiovascular physiology and immunology were performed. The outcomes of these studies are directly relevant for people working in ICE environments, but also help to better understand the biomedical challenges of those environments. Consequently, they can help to better prepare for human space exploration and to identify countermeasures to minimize the adverse effects of space environments on astronaut health. The aim of this review is to provide an overview of the biomedical studies that have taken place in the past two decades at the Antarctic Concordia station and to summarize the results and their implication for human spaceflight.

Macro- and microstructural changes in cosmonauts' brains after long-duration spaceflight.

Long-duration spaceflight causes widespread physiological changes, although its effect on brain structure remains poorly understood. In this work, we acquired diffusion magnetic resonance imaging to investigate alterations of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) compositions in each voxel, before, shortly after, and 7 months after long-duration spaceflight. We found increased WM in the cerebellum after spaceflight, providing the first clear evidence of sensorimotor neuroplasticity. At the region of interest level, this increase persisted 7 months after return to Earth. We also observe a widespread redistribution of CSF, with concomitant changes in the voxel fractions of adjacent GM. We show that these GM changes are the result of morphological changes rather than net tissue loss, which remained unclear from previous studies. Our study provides evidence of spaceflight-induced neuroplasticity to adapt motor strategies in space and evidence of fluid shift-induced mechanical changes in the brain.