Functional Gradients of the Neuraxis: Reorganization from Cortex to Spinal Cord

Overview

1. Neuro-X Institute, École Polytechnique Fédérale de Lausanne (EPFL), Geneva, 1202, Switzerland
2. Department of Radiology and Medical Informatics, University of Geneva, Geneva, 1211, Switzerland
3. Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada

Abstract

Gradient mapping has emerged as a powerful approach to summarize high-dimensional functional connectivity into low-dimensional manifolds, revealing hierarchical organization across multiple cortical and subcortical structures. Yet the spinal cord, an essential processing hub for sensorimotor integration, has remained largely absent from this dimensional view of functional organization. Here we use simultaneous corticospinal resting-state fMRI and functional connectivity gradients to place human sensorimotor cortex and cervical spinal cord within a common corticospinal manifold. We show that intrinsic cortical gradients recover key features of somatotopic organization along the sensorimotor strip, whereas spinal gradients exhibit orderly separation of gray and white matter, and of ascending and descending pathways when their geometry respects major anatomical compartments. Furthermore, by contrasting gradients that prioritize structural compartments with those that emphasize functional coupling, we show that corticospinal hierarchies depend jointly on local anatomy and cross-anatomy connectivity. Along this topographic spectrum, spinal input broadens and differentiates cortical gradients axes, while cortical input preserves spinal ones, revealing asymmetric embedding of cortex and cord at rest. Together, these findings incorporate the spinal cord into the gradient-based toolkit for mesoscale brain mapping and extend this approach beyond the cortex, providing an integrated framework in which corticospinal organization is described not as isolated regions and anatomical pathways, but as coupled manifolds spanning the neuraxis.

Reproduced under the paper's license (CC BY), from the paper cited above.

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The datasets generated and analyzed during the current study are available upon request. The code used for data pre-processing and analysis will be made available for public use.

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Version 1, 27 September 2026: the first record

Recorded: type, journal, dates, 4 authors, 5 keywords, 1 funder, 52 references.

Cite

This paper

Sareen, E., Nambiar, N. S., Bernhardt, B. C., & Van De Ville, D. (2026). Functional Gradients of the Neuraxis: Reorganization from Cortex to Spinal Cord. Research Square (preprint). https://doi.org/10.21203/rs.3.rs-10155262/v1

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