Right time, right place: Heterochronicity shapes brain network formation

Brain network formation unfolds on a non-uniform developmental timetable, with different cortical regions generating connections at different developmental phases. Generative network models (GNMs) aim to uncover the principles underpinning the organisation of connectomes by creating synthetic networks according to simple computational rules. These models capture the connectomes topology, operationalised here as the overall distributions of network metrics (e.g., modularity, small-worldness, rich-club structure). However, they typically ignore the differential timing of connectivity formation. By omitting this temporal programme, GNMs often misplace topological features in physical space. Here, we add a heterochronous growth term to GNMs and use a new model fitness function that weighs topology and topography equally. Topography refers to the spatial embedding of the network, the actual anatomical positions of 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, and converge on a single caudal-to-rostral gradient of brain maturation. Integrating heterochronicity makes GNMs more faithful to brain development, setting the stage for using them to explain and ultimately predict individual differences in network formation.