Brain Myelin Covariance Networks: Gradients, Cognition, and Higher-Order Landscape

Myelin is essential for efficient neural signaling and can be quantitatively evaluated using the T1-weighted/T2-weighted (T1w/T2w) ratio as a proxy for regional myelin content. Myelin covariance networks (MCNs) reflect correlated myelin patterns across brain regions, enabling the investigation of topological organization. However, a vertex-level map of myelin covariance gradients and their cognitive associations remains underexplored. The objective of this study was to construct and characterize vertex-level MCNs, identify their principal gradients, map their higher-order topological landscape, and determine their associations with cognitive functions and other multimodal cortical features. We conducted a cross-sectional, secondary analysis of publicly available data from the Human Connectome Project (HCP). The dataset included T1w/T2w MRI data from 1096 healthy adult participants (age 22-37). All original data collection and sharing procedures were approved by the Washington University institutional review board. Our procedures involved (1) constructing a vertex-wise MCN from T1w/T2w ratio data; (2) applying gradient analysis to identify principal organizational axes; (3) calculating network connectivity strength; (4) performing cognitive meta-analysis using Neurosynth; and (5) using graphlet analysis to assess higher-order topology. Our results show that the primary myelin gradient (Gradient 1) spans from sensory-motor to association cortices, strongly associates with connectivity strength (r = 0.66), and shows a functional dissociation between affective processing and sensorimotor domains. Furthermore, Gradient 2, as well as the positive and full connectivity strength, showed robust correlations with fractional anisotropy (FA), a DTI metric reflecting white matter microstructure. Our higher-order analysis also revealed that negative and positive myelin covariance connections exhibited distinct topologies. Negative connections were dominated by star-like graphlet structures, while positive connections were dominated by path-like and triangular structures. This systematic vertex-level investigation offers novel insights into the organizational principles of cortical myelin, linking gray matter myelin patterns to white matter integrity, and providing a valuable reference for neuropsychological research and the potential identification of biomarkers for neurological disorders.