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Heterochronicity shapes brain network formation.

Created on 13 Oct 2026

Authors

Francesco Poli, Stuart Oldham, Alexa Mousley, Edward T Bullmore, Petra E Vértes, Duncan E Astle

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 42. Pages e2610400123. Oct 20, 2026. Epub Oct 12, 2026.

Abstract

Brain network formation unfolds on a nonuniform developmental timetable, with different cortical regions generating connections at different developmental phases. Generative network models (GNMs) aim to uncover the principles underpinning the organization of connectomes by creating synthetic networks according to simple computational rules. These models capture the connectome's topology, operationalized here as the cumulative distributions of network metrics (e.g., modularity, small-worldness, rich-club structure). However, GNMs typically ignore the differential timing of connectivity formation, and by omitting this temporal programme they often misplace topological features in physical space. Here, we add a heterochronous growth term to GNMs and use a model fitness function that weighs topology and topography equally. Topography refers to the spatial embedding of the network-the actual anatomical positions of the axonal tracts. With these advances, we can generate synthetic networks that more faithfully reproduce the spatial layout of diffusion-MRI connectomes from two independent adult cohorts. Compared with classical, temporally agnostic models, heterochronous simulations improve model fit, accurately locate cortical hubs and modules across individuals, and converge on a single caudal-to-rostral gradient of brain maturation. Overall, integrating heterochronicity makes GNMs more faithful to brain development, and allows for better identification of individual differences in network formation.

PMID:
42863075
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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