Hierarchical and lateralized functional network organization of the tripartite insula: A meta-analytic connectivity...

Although the insula exhibits pronounced structural and functional heterogeneity, the large-scale organizational principles and internal coordination among its subregions remain incompletely understood. Using task-based functional neuroimaging data from healthy individuals archived in the BrainMap database, we applied meta-analytic connectivity modeling (MACM) to characterize the whole-brain coactivation networks associated with the three functionally defined insular subregions: the dorsal anterior insula (dAI), ventral anterior insula (vAI), and posterior insula (PI). By integrating functional decoding with transcriptomic analyses, we found that the tripartite insula may exhibit a hierarchical rather than strictly segregated organizational architecture. Specifically, the PI showed relatively restricted coactivation patterns primarily associated with perceptual processing; the vAI exhibited the most extensive intra-insular connectivity and may serve as a hub for emotion-related functions; whereas the dAI demonstrated the most widespread whole-brain coactivation and prominent interhemispheric coupling, being broadly involved in executive control and cognitive regulation. At the same time, coactivation patterns among the three insular subregions exhibited pronounced contralateral coupling and hemispheric asymmetry, with the right PI-vAI forming a lateralized intra-insular functional network. Collectively, the insula comprises subregions with distinct connectivity profiles and molecular signatures, while a putative hierarchical organization of intra- and extrainsular connectivity, stable interhemispheric coupling between homologous subregions, and pronounced hemispheric asymmetry in intra-insular connectivity may jointly provide the neural substrate for its broad and complex functional repertoire.