Amygdala-prefrontal connectivity in children with maladaptive aggression is modulated by social impairment

Abstract

Aggressive behavior is common across childhood-onset psychiatric disorders and is associated with impairments in social cognition and communication. The present study examined whether amygdala connectivity and reactivity during face emotion processing in children with maladaptive aggression are moderated by social impairment. This cross-sectional study included a well-characterized transdiagnostic sample of 101 children of age 8-16 years old with clinically significant levels of aggressive behavior and 32 typically developing children without aggressive behavior. Children completed a face emotion perception task of fearful and calm faces during functional magnetic resonance imaging. Aggressive behavior and social functioning were measured by standardized parent ratings. Relative to controls, children with aggressive behavior showed reduced connectivity between the amygdala and the dorsolateral prefrontal cortex (PFC) during implicit emotion processing. In children with aggressive behavior, the association between reduced amygdala-ventrolateral PFC connectivity and greater severity of aggression was moderated by greater social impairment. Amygdala reactivity to fearful faces was also associated with severity of aggressive behavior for children without social deficits but not for children with social deficits. Social impairments entail difficulties in interpreting social cues and enacting socially appropriate responses to frustration or provocation, which increase the propensity for an aggressive response via diminished connectivity between the amygdala and the ventral PFC.

Keywords: amygdala functional connectivity; dorsolateral prefrontal cortex; maladaptive aggression; social impairment; ventral prefrontal cortex.

Figure 1

Reduced amygdala–prefrontal connectivity in children with aggressive behavior. Decreased levels of connectivity were observed between the right amygdala and the right dorsolateral prefrontal cortex (PFC) in children with aggressive behavior (n = 101) compared with healthy controls (n = 32) during implicit emotion processing (A). Hyperconnectivity between the right amygdala and the left visual association cortex was observed for children with aggressive behavior compared with healthy controls (B). Standard error is represented in bar graph error bars. The y-axis shows residualized connectivity strength with age and IQ partialled out.

Figure 2

Associations between amygdala–prefrontal connectivity and severity of aggression is modulated by social impairment in youth. In dimensional analyses restricted to the aggressive behavior group (n = 101), increasing severity of aggressive behavior and social impairment were associated with reduced connectivity between the right amygdala and the right ventrolateral prefrontal cortex (vlPFC) during implicit emotion processing after accounting for the covariance with CU traits (A). The CBCL Aggressive Behavior Scale score was used as a continuous measure of severity of aggressive behavior and the Social Responsiveness Scale—Second Edition (SRS-2) Social Communication and Interaction (SCI) score was used as a continuous measure of severity of social impairments. A 3D representation is shown for the relationships driving this interaction between the two behavioral dimensions—aggression severity (x-axis) and social impairment severity (y-axis)—and the residuals of the dependent variable amygdala–vlPFC connectivity (z-axis), after adjusting for age, IQ, and CU traits (B). To visualize the interaction effects, mean extracted values for the significant vlPFC cluster are plotted separately by severity of social impairment using a median split T-score of 65 on the SRS-2 SCI subscale to form low social impairment (n = 49) (C) and high social impairment (n = 52) (D) subgroups. The y-axis represents predicted connectivity strength with the effects of age, IQ, and CU traits partialled out.

Figure 3

Amygdala reactivity to fearful faces is associated with severity of aggressive behavior in youth. In the aggressive behavior group (n = 101), results of regression analyses revealed a significant CBCL Aggressive Behavior × SRS-2 SCI interaction for right amygdala reactivity to fearful versus calm faces. That is, right amygdala reactivity to fearful faces was associated with severity of aggressive behavior for children with aggression without social deficits (β = −1.1, t = −2.1, P = 0.04) but not for children with aggression with social deficits (P > 0.1) after controlling for age, IQ, and CU traits. The x-axis shows CBCL Aggressive Behavior Scale scores, which was used as a continuous measure of severity of aggression. The y-axis shows residualized amygdala reactivity with age, IQ, and CU traits partialled out. The left panel shows the right amygdala region-of-interest, which was structurally defined using the Harvard-Oxford atlas in FSL. For visualization, scatterplots display a median split using a T-score of 65 on the SRS-2 SCI subscale.