The brain function is a network phenomenon. However, exactly how brain network reconfigures when a brain region stops functioning is virtually unknown. By combining chemogenetic and resting-state fMRI methods in an awake rats, we investigated the causal impact of inactivating a hub region, dorsal anterior cingulate cortex on brain network properties. We found that disrupting hub activity changed organization of the default-mode network (DMN) and DMN-related behavior. It also altered topological architecture of the whole-brain network. Our study established a system that allows for mechanistically dissecting the relationship between local regions and the whole brain network organization.