Functional-based parcellation of the mouse prefrontal cortex for network perturbation analysis

The prefrontal cortex (PFC) is a brain region involved in higher-order cognitive processes such as attention, emotional regulation, and social behavior. However, the delineation of distinct subdivisions within the mouse PFC and their contributions to the broader brain network function remain debated. This study utilizes resting-state functional magnetic resonance imaging (MRI) from a cohort of 100 C57BL/6J wild-type mice to derive the functional connectivity (FC)-based parcellation of the mouse PFC with voxel resolution. Our findings reveal clusters that deviate from the established anatomical subdivisions within the cingulate and prelimbic areas while aligning in infralimbic and orbital cortices. Upon the chemogenetic perturbation of one of the clusters, FC perturbations occur only within the functional network linked to the targeted cluster and do not spread to neighboring anatomical areas or functional clusters. We propose FC-based parcellation as a valuable approach for tracking the site of activation and network impact of neurostimulation strategies.