The role of the prefrontal cortex in modulating aggression in humans and rodents

Accumulating evidence suggests that the prefrontal cortex (PFC) plays an important role in aggression. However, the findings regarding the key neural mechanisms and molecular pathways underlying the modulation of aggression by the PFC are relatively scattered, with many inconsistencies and areas that would benefit from exploration. Here, we highlight the relationship between the PFC and aggression in humans and rodents and describe the anatomy and function of the human PFC, along with homologous regions in rodents. At the molecular level, we detail how the major neuromodulators of the PFC impact aggression. At the circuit level, this review provides an overview of known and potential subcortical projections that regulate aggression in rodents. Finally, at the disease level, we review the correlation between PFC alterations and heightened aggression in specific human psychiatric disorders. Our review provides a framework for PFC modulation of aggression, resolves several intriguing paradoxes from previous studies, and illuminates new avenues for further study.