Myeloarchitecture gradients in the human insula serve as blueprints for its diverse connectivity and function
AO_SCPLOWBSTRACTC_SCPLOWInsular cortex is a core hub involved in multiple cognitive and socio-affective processes. Yet, the anatomical mechanisms that explain how it is involved in such a diverse array of functions remain incompletely understood. Here, we define a novel framework to test the hypothesis that changes in myeloarchitecture across the insular cortex explain how it can be involved in many different facets of cognitive function. Detailed intracortical profiling, performed across hundreds of insular locations on the basis of myelin-sensitive magnetic resonance imaging (MRI), was compressed into a lower-dimensional space uncovering principal axes of myeloarchitectonic variation. Leveraging two datasets with different high-resolution MRI contrasts, we obtained robust support for two principal dimensions of insular myeloarchitectonic differentiation in vivo, one running from ventral anterior to posterior banks and one radiating from dorsal anterior towards both ventral anterior and posterior subregions. Analyses of post mortem 3D histological data showed that the antero-posterior axis was mirrored in cytoarchitectural markers, even when controlling for anatomical landmarks and sulco-gyral folding. Resting-state functional connectomics in the same individuals and ad hoc meta-analyses showed that myelin gradients in the insula constrained affiliation to macroscale intrinsic functional systems, showing differential shifts in functional network embedding across each myelin-derived gradient. Collectively, our findings offer a novel approach to capture structure-function interactions of a key node of the limbic system, and suggest a multidimensional structural basis underlying the diverse functional roles of the insula.