Mapping lesion-related human aggression to a common brain network.

Background: Aggression exacts a significant toll on human societies and is highly prevalent among neuropsychiatric patients for which neural mechanisms are unclear and treatment options are limited.

Methods: Using recently validated lesion network mapping technique, we derived an aggression associated network by analyzing 182 patients who had suffered penetrating head injuries during their service in the Vietnam War. To test whether damage to this lesion-derived network would increase the risk of aggression related neuropsychiatric symptoms, we used the Harvard Lesion Repository (N = 928). To explore potential therapeutic relevance of this network, we used an independent Deep brain stimulation dataset of 25 patients with epilepsy, in which irritability and aggression are known potential side effects.

Results: We found that lesions associated with aggression occurred in many different brain locations but were characterized by a specific brain network defined by functional connectivity to a hub region in the right prefrontal cortex (PFC). This network involves positive connectivity to the ventromedial PFC, dorsolateral PFC, frontal pole, posterior cingulate cortex, anterior cingulate cortex, temporal-parietal junction, and lateral temporal lobe and negative connectivity to the amygdala, hippocampus, insula, and visual cortex. Among all 25 neuropsychiatric symptoms included in the Harvard Lesion Repository, criminality demonstrated the most alignment with our aggression associated network. DBS site connectivity to this same network was associated with increased irritability.

Conclusions: We conclude that brain lesions associated with aggression map to a specific human brain circuit, and the functionally connected regions in this circuit provide testable targets for therapeutic neuromodulation.