Insula functional connectivity development follows a canonical antero-posterior axis of organization
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.
Authors
- Steven L. Meisler (ORCID: https://orcid.org/0000-0002-8888-1572)
- Leah H. Somerville (ORCID: https://orcid.org/0000-0002-3747-6884)
- Aaron F. Alexander‐Bloch (ORCID: https://orcid.org/0000-0001-6554-1893)
- Jeff Goldsmith (ORCID: https://orcid.org/0000-0002-6150-8997)
- Deanna M. Barch (ORCID: https://orcid.org/0000-0003-1693-8506)
- Audrey C. Luo (ORCID: https://orcid.org/0000-0001-6798-1876)
- Tien T. Tong (ORCID: https://orcid.org/0000-0002-1940-3198)
- Russell Taki Shinohara (ORCID: https://orcid.org/0000-0001-8627-8203)
- Theodore Daniel Satterthwaite (ORCID: https://orcid.org/0000-0001-7072-9399)
- Golia Shafiei (ORCID: https://orcid.org/0000-0002-2036-5571)
- Ruben C. Gur (ORCID: https://orcid.org/0000-0002-9657-1996)
- Matthew Cieslak (ORCID: https://orcid.org/0000-0002-1931-4734)
- Valerie J. Sydnor (ORCID: https://orcid.org/0000-0002-8640-668X)
- Corey L. Horien (ORCID: https://orcid.org/0000-0001-6738-1029)
- Taylor Salo (ORCID: https://orcid.org/0000-0001-9813-3167)
- Lucina Q. Uddin (ORCID: https://orcid.org/0000-0003-2278-8962)
- Elizabeth A. Flook (ORCID: https://orcid.org/0000-0002-0192-0496)
Institutions
- Children's Hospital of Philadelphia (US)
- Harvard University (US)
- University of California, Los Angeles (US)
- University of Pittsburgh (US)
- Columbia University (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-10-27
- DOI
- https://doi.org/10.64898/2026.10.24.761529
- Primary Topic
- Functional Brain Connectivity Studies
- Type
- preprint
Funders
- American Academy of Child and Adolescent Psychiatry
- Klingenstein Third Generation Foundation
- National Institutes of Health
- McDonnell Center for Systems Neuroscience
- National Institute of Mental Health