Large-scale meta-analyses and network analyses of neural substrates underlying human escalated aggression

Escalated aggression represents a frequent and severe form of violence, sometimes manifesting as antisocial behavior. Driven by the pressures of modern life, escalated aggression is of particular concern due to its rising prevalence and its destructive impact on both individual well-being and socioeconomic stability. However, a consistent neural circuitry underpinning it remains to be definitively identified. Here, we addressed this issue by comparing brain alterations between individuals with escalated aggression and those without such behavioral manifestations. We first conducted a meta-analysis to synthesize previous neuroimaging studies on functional and structural alterations of escalated aggression (325 experiments, 2997 foci, 16,529 subjects). Following-up network and functional decoding analyses were conducted to provide quantitative characterizations of the identified brain regions. Our results revealed that brain regions constantly involved in escalated aggression were localized in the subcortical network (amygdala and lateral orbitofrontal cortex) associated with emotion processing, the default mode network (dorsal medial prefrontal cortex and middle temporal gyrus) associated with mentalizing, and the salience network (anterior cingulate cortex and anterior insula) associated with cognitive control. These findings were further supported by additional meta-analyses on emotion processing, mentalizing, and cognitive control, all of which showed conjunction with the brain regions identified in the escalated aggression. Together, these findings advance the understanding of the risk biomarkers of escalated aggressive populations and refine theoretical models of human aggression.