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Long-duration spaceflight poses a variety of health risks to astronauts, largely resulting from extended exposure to microgravity and radiation. Here, we assessed the prevalence and incidence of cerebral microbleeds in sixteen astronauts before and after a typical 6-month mission on board the International Space Station Cerebral microbleeds are microhemorrhages in the brain, which are typically interpreted as early evidence of small vessel disease and have been associated with cognitive impairment. We identified evidence of higher-than-expected microbleed prevalence in astronauts with prior spaceflight experience. However, we did not identify a statistically significant increase in microbleed burden up to 7 months after spaceflight. Altogether, these preliminary findings suggest that spaceflight exposure may increase microbleed burden, but this influence may be indirect or occur over time courses that exceed 1 year. For health monitoring purposes, it may be valuable to acquire neuroimaging data that are able to detect the occurrence of microbleeds in astronauts following their spaceflight missions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Burles, Willson, Townes, Yang and Iaria.)

INTRODUCTION: The rapid development of the space industry requires a deeper understanding of spaceflight's impact on the brain. MRI research reports brain volume changes following spaceflight in astronauts, potentially affecting cognition. Recently, we have demonstrated that this evidence of volumetric changes, as measured by typical T1-weighted sequences (e.g., magnetization-prepared rapid gradient echo sequence; MPRAGE), is error-prone due to the microgravity-related redistribution of cerebrospinal fluid in the brain. More modern neuroimaging methods, particularly dual-echo MPRAGE (DEMPRAGE) and magnetization-prepared rapid gradient echo sequence utilizing two inversion pulses (MP2RAGE), have been suggested to be resilient to this error. Here, we tested if these imaging modalities offered consistent segmentation performance improvements in some commonly employed neuroimaging software packages. METHODS: We conducted manual gray matter tissue segmentation in traditional T1w MRI images to utilize for comparison. Automated tissue segmentation was performed for traditional T1w imaging, as well as on DEMPRAGE and MP2RAGE images from the same subjects. Statistical analysis involved a comparison of total gray matter volumes for each modality, and the extent of tissue segmentation agreement was assessed using a test of similarity (Dice coefficient). RESULTS: Neither DEMPRAGE nor MP2RAGE exhibited consistent segmentation performance across all toolboxes tested. DISCUSSION: This research indicates that customized data collection and processing methods are necessary for reliable and valid structural MRI segmentation in astronauts, as current methods provide erroneous classification and hence inaccurate claims of neuroplastic brain changes in the astronaut population. Berger L, Burles F, Jaswal T, Williams R, Iaria G. Modern magnetic resonance imaging modalities to advance neuroimaging in astronauts . Aerosp Med Hum Perform. 2024; 95(5):245-253.

Despite a decade-long study on Developmental Topographical Disorientation, the underlying mechanism behind this neurological condition remains unknown. This lifelong selective inability in orientation, which causes these individuals to get lost even in familiar surroundings, is present in the absence of any other neurological disorder or acquired brain damage. Herein, we report an analysis of the functional brain network of individuals with Developmental Topographical Disorientation ($n = 19$) compared against that of healthy controls ($n = 21$), all of whom underwent resting-state functional magnetic resonance imaging, to identify if and how their underlying functional brain network is altered. While the established resting-state networks (RSNs) are confirmed in both groups, there is, on average, a greater connectivity and connectivity strength, in addition to increased global and local efficiency in the overall functional network of the Developmental Topographical Disorientation group. In particular, there is an enhanced connectivity between some RSNs facilitated through indirect functional paths. We identify a handful of nodes that encode part of these differences. Overall, our findings provide strong evidence that the brain networks of individuals suffering from Developmental Topographical Disorientation are modified by compensatory mechanisms, which might open the door for new diagnostic tools., (© The Author(s) 2024. Published by Oxford University Press.)

Developmental topographical disorientation (DTD) refers to the lifelong inability to orient by means of cognitive maps in familiar surroundings despite otherwise well-preserved general cognitive functions, and the absence of any acquired brain injury or neurological condition. While reduced functional connectivity between the hippocampus and other brain regions has been reported in DTD individuals, no structural differences in gray matter tissue for the whole brain neither for the hippocampus were detected. Considering that the human hippocampus is the main structure associated with cognitive map-based navigation, here, we investigated differences in morphological and morphometric hippocampal features between individuals affected by DTD (N = 20) and healthy controls (N = 238). Specifically, we focused on a developmental anomaly of the hippocampus that is characterized by the incomplete infolding of hippocampal subfields during fetal development, giving the hippocampus a more round or pyramidal shape, called incomplete hippocampal inversion (IHI). We rated IHI according to standard criteria and extracted hippocampal subfield volumes after FreeSurfer's automatic segmentation. We observed similar IHI prevalence in the group of individuals with DTD with respect to the control population. Neither differences in whole hippocampal nor major hippocampal subfield volumes have been observed between groups. However, when assessing the IHI independent criteria, we observed that the hippocampus in the DTD group is more medially positioned comparing to the control group. In addition, we observed bigger hippocampal fissure volume for the DTD comparing to the control group. Both of these findings were stronger for the right hippocampus comparing to the left. Our results provide new insights regarding the hippocampal morphology of individuals affected by DTD, highlighting the role of structural anomalies during early prenatal development in line with the developmental nature of the spatial disorientation deficit., (© 2024 Wiley Periodicals LLC.)

The ability to navigate and orient in spatial surroundings is critical for effective daily functioning. Such ability is perturbed in clinically diagnosed mood and anxiety disorders, with patients exhibiting poor navigational skills. Here, we investigated the effects of depression and anxiety traits (not the clinical manifestation of the disorders) on the healthy population and hypothesized that greater levels of depression and anxiety traits would manifest in poorer spatial orientation skills and, in particular, with a poor ability to form mental representations of the environment, i.e., cognitive maps. We asked 1237 participants to perform a battery of spatial orientation tasks and complete two questionnaires assessing their anxiety and depression traits. Contrary to our hypothesis, we did not find any correlation between participants' anxiety and depression traits and their ability to form cognitive maps. These findings may imply a significant difference between the clinical and non-clinical manifestations of anxiety and depression as affecting spatial orientation and navigational abilities.

Astronauts often face orientation challenges while on orbit, which can lead to operator errors in demanding spatial tasks. In this study, we investigated the impact of long-duration spaceflight on the neural processes supporting astronauts' spatial orientation skills. Using functional magnetic resonance imaging (fMRI), we collected data from 16 astronauts six months before and two weeks after their International Space Station (ISS) missions while performing a spatial orientation task that requires generating a mental representation of one's surroundings. During this task, astronauts exhibited a general reduction in neural activity evoked from spatial-processing brain regions after spaceflight. The neural activity evoked in the precuneus was most saliently reduced following spaceflight, along with less powerful effects observed in the angular gyrus and retrosplenial regions of the brain. Importantly, the reduction in precuneus activity we identified was not accounted for by changes in behavioral performance or changes in grey matter concentration. These findings overall show less engagement of explicitly spatial neurological processes at postflight, suggesting astronauts make use of complementary strategies to perform some spatial tasks as an adaptation to spaceflight. These preliminary findings highlight the need for developing countermeasures or procedures that minimize the detrimental effects of spaceflight on spatial cognition, especially in light of planned long-distance future missions.

Which facets of human spatial navigation do sex and menstrual cycle influence? To answer this question, a cross-sectional online study of reproductive age women and men was conducted in which participants were asked to demonstrate and self-report their spatial navigation skills and strategies. Participants self-reported their sex and current menstrual phase [early follicular (EF), late follicular/periovulatory (PO), and mid/late luteal (ML)], and completed a series of questionnaires and tasks measuring self-reported navigation strategy use, topographical memory, cognitive map formation, face recognition, and path integration. We found that sex influenced self-reported use of cognitive map- and scene-based strategies, face recognition, and path integration. Menstrual phase moderated the influence of sex: compared to men, women had better face recognition and worse path integration, but only during the PO phase; PO women were also better at path integration in the presence of a landmark compared to EF + ML women and men. These findings provide evidence that human spatial navigation varies with the menstrual cycle and suggest that sensitivity of the entorhinal cortex and longitudinal axis of the hippocampus to differential hormonal effects may account for this variation., (© 2023. Springer Nature Limited.)

After completing a spaceflight, astronauts display a salient upward shift in the position of the brain within the skull, accompanied by a redistribution of cerebrospinal fluid. Magnetic resonance imaging studies have also reported local changes in brain volume following a spaceflight, which have been cautiously interpreted as a neuroplastic response to spaceflight. Here, we provide evidence that the grey matter volume changes seen in astronauts following spaceflight are contaminated by preprocessing errors exacerbated by the upwards shift of the brain within the skull. While it is expected that an astronaut's brain undergoes some neuroplastic adaptations during spaceflight, our findings suggest that the brain volume changes detected using standard processing pipelines for neuroimaging analyses could be contaminated by errors in identifying different tissue types (i.e., tissue segmentation). These errors may undermine the interpretation of such analyses as direct evidence of neuroplastic adaptation, and novel or alternate preprocessing or experimental paradigms are needed in order to resolve this important issue in space health research.

Knowledge transfer among research disciplines can lead to substantial research progress. At first glance, astronaut health and rare diseases may be seen as having little common ground for such an exchange. However, deleterious health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases. Here, we compare and contrast research and healthcare in the contexts of rare diseases and space health and identify common barriers and avenues of improvement. The prevalent genetic basis of most rare disorders contrasts sharply with the occupational considerations required to sustain human health in space. Nevertheless small sample sizes and large knowledge gaps in natural history are examples of the parallel challenges for research and clinical care in the context of both rare diseases and space health. The two areas also face the simultaneous challenges of evidence scarcity and the pressure to deliver therapeutic solutions, mandating expeditious translation of research knowledge into clinical care. Sharing best practices between these fields, including increasing participant involvement in all stages of research and ethical sharing of standardized data, has the potential to contribute to humankind's efforts to explore ever further into space while caring for people on Earth in a more inclusive fashion., (© 2022. The Author(s).)