Regional BOLD variability reflects microstructural maturation and neuronal ensheathment in the preterm infant cortex

BOLD variability reflects meaningful brain activity, yet its structural and biological correlates during early development remain unknown. We aimed to investigate how BOLD variability evolves in very preterm (VPT) infants, its relationship with cortical microstructure and gene expression, and how it differs from full-term (FT) newborns at term-equivalent age (TEA). Using resting-state fMRI and multi-shell diffusion imaging, acquired in 54 VPT (longitudinally at 33-weeks GA and at TEA) and 24 FT newborns, we evaluated regional differences in cortical BOLD variability and microstructural maturation, and compared to patterns of gene expression in the fetal cortex, using the BrainSpan dataset. BOLD variability increased in primary sensory-sensorimotor and proto-DMN regions, accompanied by decreased cortical diffusivity. Gene expression analysis revealed concurrent upregulation of genes mediating gliogenesis and neuronal ensheathment. Compared to FT newborns, VPT at TEA showed decreased BOLD variability and increased cortical diffusivity. BOLD variability reflects cortical microstructure, mediated by upregulation of gliogenesis and neuronal ensheathment. Interruption of these processes by preterm birth identifies putative mechanisms of preterm brain injury.