Bayesian generative modeling reveals a multi-modal hierarchical architecture in the mouse functional connectome

Abstract

Understanding the principles governing large-scale functional organization of the brain remains a central challenge in systems neuroscience. Despite convergent findings, substantial variability across analytical approaches suggests that functional networks may not admit a unique partitioning. Here, we propose that this variability reflects an intrinsic property of the connectome itself: its organization may be fundamentally multi-modal rather than singular. To test this hypothesis, we employ a Bayesian generative modeling framework based on stochastic block models, enabling principled comparison of competing organizational principles and characterization of the full posterior distribution over network partitions. Applying this framework to resting-state fMRI data in mice, we find that a non-degree-corrected hierarchical architecture provides the most parsimonious description of the functional connectome. Importantly, the inferred posterior landscape is not dominated by a single configuration, but instead comprises multiple distinct and co-dominant organizational schemes. At the mesoscale, these hierarchical communities are anatomically grounded yet systematically reorganize canonical resting-state networks: primary sensory systems remain cohesive, whereas higher-order association networks are fractionated into multiple interacting sub-circuits. This global structural variation is driven by structured variability at the community level, where integrative systems exhibit variable regional affiliations while sensory systems act as structurally stable anchors. Together, these findings suggest that the resting-state connectome is best described as a distribution over alternative, yet co-dominant, organizational configurations. This perspective reconciles inconsistencies across previous studies and supports a view of brain organization as inherently degenerate, providing a latent repertoire of network configurations that may underlie adaptive information routing and dynamic functional reconfiguration.