Geometric influences on the regional organization of the mammalian brain

Pang, J. C.; Robinson, P. A.; Aquino, K. M.; Levi, P. T.; Holmes, A.; Markicevic, M.; Shen, X.; Funck, T.; Palomero-Gallagher, N.; Kong, R.; Yeo, B. T. T.; Tiego, J.; Bellgrove, M. A.; Constable, R. T.; Lake, E. M.; Breakspear, M.; Fornito, A.

doi:10.1101/2025.01.30.635820

bioRxiv · 10.1101/2025.01.30.635820

Geometric influences on the regional organization of the mammalian brain

Pang, J. C.·Robinson, P. A.·Aquino, K. M.·Levi, P. T.·Holmes, A.·Markicevic, M.·Shen, X.·Funck, T.·Palomero-Gallagher, N.·Kong, R.·Yeo, B. T. T.·Tiego, J.·Bellgrove, M. A.·Constable, R. T.·Lake, E. M.·Breakspear, M.·Fornito, A.

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Abstract

The mammalian brain comprises anatomically and functionally distinct regions, yet the principles governing their organization across scales remain unclear. Efforts to map regional boundaries use expert judgement or data-driven clustering of functional, connectional, and/or architectonic properties, but these approaches are often descriptive, have limited generalizability, and do not elucidate generative mechanisms. Here, we develop a geometrically constrained framework for the hierarchical, multiscale regional organization of neocortical and non-neocortical structures. The framework yields parcels at any resolution with high internal homogeneity across hundreds of anatomical, functional, cellular, and molecular properties in humans, macaques, marmosets, and mice, and it generalizes to understudied mammalian species. Finally, we demonstrate that the framework captures the essence of a reaction-diffusion mechanism in which brain geometry shapes the spatial expression of putative patterning molecules that establish a blueprint of regional identity during development. Our findings point to a conserved, universal influence of geometry on mammalian brain organization.

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Pang, J. C., Robinson, P. A., Aquino, K. M., Levi, P. T., Holmes, A., Markicevic, M., Shen, X., Funck, T., Palomero-Gallagher, N., Kong, R., Yeo, B. T. T., Tiego, J., Bellgrove, M. A., Constable, R. T., Lake, E. M., Breakspear, M., Fornito, A.. 2025-02-01. Geometric influences on the regional organization of the mammalian brain. https://doi.org/10.1101/2025.01.30.635820

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