Objective:

To identify whether there are specific brain networks associated with lesion-induced aggressive behavior.

Background:

Aggression, encompassing physical or verbal harm or threat to oneself or others, is common in many neurodevelopmental and psychiatric conditions. Aggressive behavior can have a profound impact on patients and their caregivers, however the neuroanatomical basis of aggression is unclear. Neuroimaging studies have implicated numerous brain regions in aggressive behavior but have been unable to clarify whether these differences are causal or compensatory. Here, we use lesion network mapping to identify convergence across the existing literature of brain injury causing aggressive behavior.

Design/Methods:

From the clinical literature, we identified 59 case reports (with imaging) detailing focal brain injury  associated with new-onset aggression, agitation, and/or irritability. We traced these lesions onto a standardized brain atlas, then generated maps of functional connectivity for each lesion by leveraging resting state data from 1000 healthy young adults. These maps were statistically compared to a large dataset of lesions associated with other neuropsychiatric syndromes as well as subjected to clustering analysis.

Results:

We found that while lesions causing aggression vary in location, they localize to a specific brain network that is connected to the ventromedial prefrontal cortex, temporal lobes, and amygdala. When compared to other neuropsychiatric conditions, we found increased positive connectivity to the orbitofrontal cortex and increased negative connectivity to the thalamus and insula. Clustering the lesion functional connectivity maps revealed two subclasses of patients. Based on clinical descriptions, one of these classes appears to be associated with criminal behavior while the other is more associated with irritability and agitation, each with a distinct neuroanatomical localization.

Conclusions:

Lesions that are associated with new-onset aggression appear to impact a core set of brain networks that are specific to aggressive behavior. Intriguingly, cases appear to cluster into two distinct groups with unique neuroanatomical and behavioral phenotypes.