Neural fiber orientations across spinal cord gray matter

<jats:p>Understanding connectivity within the nervous system is central to understanding its function, and the network architecture of many brain regions has been mapped in fine detail. The sub-tract organization of neuronal projections within the human cord, particularly in gray matter is essentially unknown. Since full connectomic reconstruction is currently intractable at this scale, a tractable first step is to statistically characterize neurite orientations across spinal regions. Here we combine a ~400 hour 9.4T ex vivo high-angular-resolution diffusion-weighted MRI spanning all segments (C1-S5) of a post-mortem human spinal cord with structure-tensor analysis of SMI-32 neurofilament fluorescence microscopy to map neurite orientation across the cord. We find that projection geometry varies systematically along the rostro-caudal axis. Cervical, lumbar, and sacral gray matter exhibit low anisotropy, high orientation dispersion, and predominantly transverse fiber populations (&gt;91% of orientations), consistent with dense segment-local circuitry. Thoracic gray matter is categorically distinct from the rest of the cord with elevated axial diffusivity, white-matter-like anisotropy, and a fiber orientation distribution in which 60% of orientations run within a polar angle of 85-95° i.e., along the the cord's rostro-caudal axis. Micron-resolution microscopy independently supports this longitudinal architecture. Together, these findings reveal a regional dissociation in spinal gray-matter wiring and suggest a coupling between projection geometry and the distinct processing demands of each segment.</jats:p>