A reproducible low-dimensional architecture of human white-matter connectivity

Abstract

The human brain is organized by large-scale functional gradients, but whether white-matter connectivity defines similarly reproducible and biologically interpretable axes of cortical, subcortical, and cerebellar organization remains unclear. Here, we introduce Structural Connectivity Gradient Mapping (SCGM), a framework for deriving low-dimensional structural connectivity gradients from diffusion MRI tractography using a whole-brain parcellation spanning 438 cortical, subcortical, and cerebellar regions. Across repeated scans, an independent onsite cohort, and the Human Connectome Project Young Adult cohort, SCGM-derived gradients were highly reproducible and robust across datasets. Four dominant gradients captured most structural-connectivity variance and mapped onto distinct anatomical axes: hemispheric laterality and geometry, dorsal-ventral organization, cingulate-temporal organization, and a cerebellar-transmodal axis. Despite their reliability, structural gradients showed only limited correspondence with functional connectivity gradients, indicating that white-matter architecture and functional organization capture partly distinct dimensions of brain organization. Age effects were strongest for higher-order structural gradients, particularly the cerebellar-transmodal axis, where older age was associated with reduced separation between cerebellar and transmodal cortical parcels. These findings identify a reproducible low-dimensional architecture of human white-matter connectivity, establish SCGM as a framework for mapping structural-connectivity gradients, and reveal age-related remodeling of a cerebellar-transmodal axis linking distributed cortical and cerebellar systems.