Brain network reorganization after targeted attack at a hub region

The architecture of brain networks has been extensively studied in multiple species. However, exactly how the brain network reconfigures when a local region, particularly a hub region, stops functioning remains elusive. By combining chemogenetics and resting-state functional magnetic resonance imaging (rsfMRI) in an awake rodent model, we investigated the causal impact of acutely inactivating a hub region (i.e. the dorsal anterior cingulate cortex) on brain network properties. We found that suppressing neural activity in a hub could have a ripple effect that went beyond the hub-related connections and propagated to other neural connections across multiple brain systems. In addition, hub dysfunction affected the topological architecture of the whole-brain network in terms of the network resilience and segregation. Selectively inhibiting excitatory neurons in the hub further changed network integration. None of these changes were observed in sham rats or when a non-hub region (i.e. the primary visual cortex) was perturbed. This study has established a system that allows for mechanistically dissecting the relationship between local regions and brain network properties. Our data provide direct evidence supporting the hypothesis that acute dysfunction of a brain hub can cause large-scale network changes. These results also provide a comprehensive framework documenting the differential impact of hub versus non-hub nodes on network dynamics.