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Long-term effects of simulated microgravity in the central nervous system of rhesus monkeys: a voxel-wise multimodal MRI study

Jiarui Wang,Dong Zheng,Chenhao Zhao,Xuan Xuan,Xiaoyun Zhang,Ruyue Li,Kai-Feng Xu,Yawei Zeng,Youping Tao,Dongxu Lu,Li Liu,Suping Zhao,Yanli Liu,Jigong Wu,Juan Du

Published 2025 in Frontiers in Physiology

ABSTRACT

Background With the development of spaceflight, scientists have gradually realized that long-term microgravity can alter the brain’s structure, which may affect the stability of brain function and, in turn, cognition and many other behaviors. Objective By quantitatively analyzing the effects of microgravity on brain gray matter volume, fiber tracts, and resting-state neural functional activity, this study preliminarily explores the dynamic changes in brain tissue structure and their relationships during simulated microgravity. Methods Six male rhesus macaques were included in the study and underwent −10° head-down bed rest (HDBR) for 42 days as a terrestrial analog of the microgravity environment. Multimodal magnetic resonance imaging (MRI) was performed 3 days before HDBR, 21 days after HDBR, and 42 days after HDBR. Voxel-based morphometry (VBM) analysis was used to compare differences in brain gray matter volume. Differences in the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were investigated using tract-based spatial statistic (TBSS) analysis. Resting-state functional MRI was used to compare differences in local neural activity. Results During simulated microgravity, significant changes in gray matter volume were found in the right substantia innominate of the basal forebrain, right insula, left putamen, and left occipital gyrus. A significant decrease in FA and AD was found during simulated microgravity, specifically in the left inferior longitudinal fasciculus, left fornix, left corticospinal tract, left inferior longitudinal fasciculus, left superior longitudinal fasciculus, left frontal aslant tract, right uncinate fasciculus, and bilateral inferior fronto-occipital fasciculus regions. A significant decrease in MD and RD was widely observed in the left inferior longitudinal fasciculus, middle cerebellar peduncle, bilateral frontal aslant tract regions, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Regional homogeneity (ReHo) in the left thalamic reticular nucleus continuously increased during simulated microgravity conditions. Conclusion Using multimodality MRI, this study indicated that simulated microgravity might cause widespread abnormalities through neuroplasticity, especially in brain regions in charge of visuospatial awareness and voluntary motion. There may exist a complex functional compensation between the reconstruction of gray and white matter and the rearrangement of neural connections.

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