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

Jiarui Wang^1,2Dong Zheng³Ruyue Li^1,4Zhao Chenhao^4,5Xuan Xuan²Xiaoyun Zhang²Kai Xu³Yawei Zeng³Youping Tao⁴Dongxu Lu²Li Liu²Suping Zhao²Yanli Liu²Jigong Wu^1,4*Juan Du^1,2*

• ¹PLA 306 Clinical College, The Fifth Medical college, Anhui Medical University, Hefei, China
• ²Department of Neurology, The Ninth Medical Center of PLA General Hospital, Beijing, China
• ³Department of Imaging, The Ninth Medical Center of PLA General Hospital, Beijing, China
• ⁴Department of Spinal Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
• ⁵The Second Affiliated Hospital, Anhui Medical University, Hefei, China

Background With the development of spaceflight, scientist have gradually realized that the long-term microgravity could alter structural of brain, which could inevitably contribute to the stability of brain function, then affects cognition and many other behaviors. Objective By quantitatively analyzing the effects of microgravity on brain grey matter volume, fiber tracts, and resting-state neural functional activity, this study would preliminarily explore the dynamic changes in brain tissue structure and the relationships among these changes during simulated microgravity. Methods Six male rhesus macaques were subjected into the study and underwent -10° head-down bed rest (HDBR) for 42 days as a terrestrial analog of microgravity environment. Multimodal MRI was scanned at 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 TBSS analysis. Resting-state functional MRI was used to compare differences in local neural activity. This is a provisional file, not the final typeset article Results During simulated microgravity, significant changes of gray matter volume was found in the right substantia innominate of basal forebrain, right insula, left putamen, and left occipital gyrus. Significantly decreased FA and AD were 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. Significantly decreased 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. 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.