The orbitofrontal cortex (OFC) is widely viewed as a center for behavioral control, helping regulate emotions and suppress inappropriate actions. This has led to the idea that it acts as a cortical “brake” on aggression.
Here we test a different possibility: that the OFC can actively promote aggression under certain conditions.
We focus on a direct pathway from the medial OFC to the medial amygdala, a key node in aggression circuits. Using circuit-specific tracing, in vivo calcium imaging, and chemogenetic manipulation, we find that this pathway is excitatory, strongly activated during traumatic stress, and required for the later emergence of aggressive behavior.
These results show that the OFC does not simply inhibit subcortical circuits—it can also drive them. In this case, traumatic stress shifts OFC output toward activating aggression-promoting pathways, producing long-lasting changes in social behavior.
This work reframes the OFC as a flexible, context-dependent controller of emotional circuits rather than a simple inhibitory brake, and identifies the OFC–amygdala pathway as a potential target for treating stress-related aggression.
Mikaela L. Aholt, Jessica T. Jacobs, Magdalene P. Adjei, Nooshin Mojahed, Elana Qasem, Sandria W. Athul, Buffy Ellsworth, Jacob C. Nordman
Neuropsychopharmacology