Lesion network mapping of focal injury-related aggression finds two distinct network injury patterns

Abstract Aggressive behaviour is prevalent across neurodevelopmental and neuropsychiatric conditions and is related to poor outcomes. Yet, despite extensive neuroimaging studies, a consistent set of brain networks where dysfunction is consistently related to aggressive behaviour remains unclear. Many studies are correlational in nature, while causal studies, such a lesion-location-based studies, are often limited to injury of the frontal lobes. Here, we analyse 61 focal brain lesions, identified in the current medical literature, that are associated with new-onset aggression and related behaviours. Lesions were traced onto a standardized brain atlas and used as seeds for a functional connectivity analysis, leveraging resting-state data from 1000 healthy individuals. These maps, representing likely pre-injury connectivity, were grouped using a data-driven hierarchical clustering approach. Then, the lesion networks of the identified clusters were separately compared with the connectivity of 716 lesions causing other symptoms. This data-driven approach identified two distinct lesion subgroups that both appear to manifest aggression through the co-occurrence of disrupted functional connectivity to networks involved in emotional expression and cognitive control. Both ‘aggression networks’ demonstrated sensitivity and specificity when compared with lesions causing a wide variety of other neuropsychiatric symptoms. The first subgroup network involved connectivity to the anterior cingulate cortex and was correlated with the connectivity of lesions causing akinetic mutism. The second subgroup network involved connectivity to the ventromedial prefrontal cortex and contained a notable subset of cases (n = 25) that had reported criminal behaviour, supporting a role of self-control in this subgroup and implying separable influences towards criminality within our identified aggression networks. Alterations within the first group aligned with motivation networks, while the second group aligned with disinhibition networks, indicating these as the potential underlying factors in aggression in the two subgroups, respectively. This characterization was supported by previous work on the atrophy network mapping of behavioural variant frontotemporal dementia. Overall, this study suggests that aggressive behaviour may be more likely after injury to distinct brain networks, which may be related to distinct behavioural factors, and has implications for potential targeted therapeutic interventions such as focused neuromodulation.