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Head-down tilt bed rest (HDBR) serves as a critical analogue for microgravity-induced neural adaptations, but existing studies are limited by short durations and unimodal neuroimaging. This study integrated multimodal neuroimaging (T1-weighted magnetic resonance imaging [MRI], diffusion tensor imaging, resting-state functional MRI), neurocognitive assessments and transcriptomics to characterize central nervous system (CNS) adaptations in 13 males undergoing 60-day HDBR. Repeatable Battery for the Assessment of Neuropsychological Status revealed no global cognitive decline, but attenuated Delayed Memory compared with healthy controls ( P < 0.05). Neuroimaging identified cerebrospinal fluid (CSF) expansion ( P < 0.05) without grey/white matter changes, and right-lateralized prefrontal functional hyperactivation ( P < 0.05). Linear mixed-effects models and mediation analysis confirmed that CSF/time predicted prefrontal function, mediating CSF-induced memory changes ( P < 0.05). Imaging-genomic analyses linked these functional changes to ribosomal translation pathways ( P < 0.001). These findings provide a multiscale framework for developing countermeasures against microgravity-induced CNS maladaptations during deep-space exploration.
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Huang et al. (2026) studied this question.
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