Structural Connectivity Differences Reflect Microstructural Heterogeneity of the Human Insular Cortex.

The insular cortex is renowned for its multitude of functions, intricate structural connectivity patterns, and complex cytoarchitecture, yet a unified multimodal concept remains elusive. Microstructural parcellations provide a promising mediator to integrate connectome data into a combined structural-functional framework. While in the macaque insula, a clear relationship between anatomical connections and cytoarchitecture is well established, such correlation in the human insula remains unclear. By combining diffusion data from two large cohorts, including 914 and 204 subjects, respectively, as well as probabilistic tractography and the microstructural JulichBrain Atlas, we uncover how microstructural diversity reflects structural connectivity patterns in the human insula. Analyzing the connectivity of 16 cytoarchitectonic areas, we identified six clusters, two in the posterior and four in the anterior insula. Posterior clusters exhibited strong connectivity with temporal, occipital, and parietal areas encompassing auditory, visual, and somatosensory systems. Conversely, anterior clusters were specifically linked with (orbito)frontal areas, such as Broca's area or frontal opercular areas. Together, our data demonstrate that structural connectivity differences are reflected by fundamental principles of microstructural organization in the human insula. Additional whole-brain connectivity analyses reveal that two distinct areas within the anterior (Id6) and posterior (Id3) human insula may serve as integrative hubs, mediating between higher-order cognitive and limbic systems, as well as across sensory modalities. All clusters are openly available in MNI space to support future multimodal studies addressing the relations between cytoarchitecture, structure, functions, and pathologies in this complex region of the human neocortex.