Insula functional connectivity development follows a canonical antero-posterior axis of organization

Flook, E. A.; Shafiei, G.; Cieslak, M.; Horien, C.; Luo, A. C.; Meisler, S. L.; Salo, T.; Sydnor, V. J.; Tong, T. T.; Barch, D. M.; Goldsmith, J.; Gur, R. E.; Somerville, L. H.; Uddin, L. Q.; Alexander-Bloch, A.; Shinohara, R. T.; Satterthwaite, T. D.

doi:10.64898/2026.10.24.761529

bioRxiv · 10.64898/2026.10.24.761529

Insula functional connectivity development follows a canonical antero-posterior axis of organization

Flook, E. A.·Shafiei, G.·Cieslak, M.·Horien, C.·Luo, A. C.·Meisler, S. L.·Salo, T.·Sydnor, V. J.·Tong, T. T.·Barch, D. M.·Goldsmith, J.·Gur, R. E.·Somerville, L. H.·Uddin, L. Q.·Alexander-Bloch, A.·Shinohara, R. T.·Satterthwaite, T. D.

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Abstract

The insula is a heterogeneous region associated with a range of functional domains including sensory, cognitive, and emotional processing. Cytoarchitectural and functional studies have described an antero-posterior axis of insula organization. However, the insula's functional development remains sparsely described. We delineated the development of insula resting-state functional connectivity across 562 individuals (6-22 years) using generalized additive models and population value decomposition. We show insulo-cortical functional connectivity development differs across the insula: anterior subregions have predominantly decreasing connectivity across the age range examined, whereas posterior subregions have variable connectivity that aligns with the sensorimotor-association axis. Vertex-level analysis revealed that age-related trajectories followed an antero-posterior axis that aligned with estimates of insula microstructure. Our results emphasize that the development of insula connectivity is spatially heterogeneous and aligns with known cytoarchitecture. The normative insula development described here provides a foundation for investigating how emerging psychopathology may be linked to variation in insula development.

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Flook, E. A., Shafiei, G., Cieslak, M., Horien, C., Luo, A. C., Meisler, S. L., Salo, T., Sydnor, V. J., Tong, T. T., Barch, D. M., Goldsmith, J., Gur, R. E., Somerville, L. H., Uddin, L. Q., Alexander-Bloch, A., Shinohara, R. T., Satterthwaite, T. D.. 2026-10-27. Insula functional connectivity development follows a canonical antero-posterior axis of organization. https://doi.org/10.64898/2026.10.24.761529

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