Poster #19 - Neural Response to Provocation and Reactive Aggression: The Moderating Role of Callous-Unemotional Traits.

• In Event: 3-003 - Poster Session 09
  In Poster Session: PS 09 Section - Biological Processes: Neuroscience and Genetics

Integrative Statement

Background: Maladaptive reactive aggression is an important clinical concern, particularly in youth with Disruptive Behavior Disorders (DBDs; including Conduct Disorder and Oppositional Defiant Disorder). However, youth with DBDs and high levels of callous-unemotional traits (i.e., lack empathy, remorse, callous use of others) and youth with DBDs and low levels of callous-unemotional traits are theorized to engage in reactive aggression due to different pathophysiology (Blair, 2012). Previous work found increasing amygdala and periaqueductal gray (PAG) response and diminished ventromedial prefrontal cortex (vmPFC) response with increasing retaliatory behavior in in youth with DBDs and low levels of CU traits during a social provocation paradigm. Reactive aggression was not directly linked to neural responses, however.

Methods: One-hundred-forty-nine youth (88 with DBDs) completed a social provocation paradigm during fMRI. Participants are offered either a fair ($10 to participant; $10 to partner) or unfair ($6/$4/$2 to participant; $14/$16/$18 to partner) division of a $20 pot. Participants could then either accept the offer or reject it and, by spending $1, $2 or $3 punishment dollars, punish the partner. Each punishment dollar spent by the participant caused the partner to lose $7 from the $20 pot (Figure 1; White, Brislin, et al, 2014; White, Vanteighem, et al, 2016). Parent report of reactive aggression and CU traits were obtained. Two analyses were conducted. First, the neural systems involved in mediating and regulating retaliatory responses to social provocation in neuro-typical youth were defined by significant activation observed in 20 typically developing youth. Linear regression analysis using reactive aggression and CU traits as predictors of BOLD response within each of the task relevant regions was conducted within the remaining sample (41 typically developing youth, 88 youth with DBDs). Second, a whole brain analysis examining reactive aggression and CU traits continuously was conducted only within the 88 youth with DBDs. All fMRI clusters were corrected to p=.05 using 3dClustSim (k=24, initial threshold: p=.002)

Results: Group membership, CU traits and reactive aggression all failed to show a significant association with punishment level selected [F= .00 to 1.12, p>.29]. Within the task-relevant regions, reactive aggression, but not CU traits, was associated with increased BOLD response within regions implicated in cognitive control (dorsolateral prefrontal and dorsomedial frontal cortex, anterior insula cortex, inferior frontal gyrus), but not PAG or vmPFC. In the whole-brain analysis, greater reactive aggression was associated with increased PAG response and diminished vmPFC at low, but not high, levels of CU traits (figure 2).

Discussion: These data show an association between increased PAG/diminished vmPFC responses and reactive aggression in humans. These data, consistent with theory, suggest that maladaptive reactive aggression is associated with different pathophysiology in youth with DBDs and low versus high levels of CU traits. Furthermore, greater levels of reactive aggression were associated with increased recruitment of cognitive control to get equivalent task performance, suggesting that greater cognitive resources were need to control response to social provocation in youth with high reactive aggression ratings.

Authors

• Stuart F. White, Boys Town National Research Hospital
  Presenting Author

• Laura C Thornton, Boys Town National Research Hospital
  Non-Presenting Author

• Emily K. Leiker, Boys Town National Research Hospital
  Non-Presenting Author

• Brittany K. Taylor, Boys Town National Research Hospital
  Non-Presenting Author

• Kimberly R. Johnson, Boys Town National Research Hospital
  Non-Presenting Author

• Heba Abdel-Rahim, Boys Town National Research Hospital
  Non-Presenting Author

• Patrick M. Tyler, Boys Town National Research Hospital
  Non-Presenting Author

• Matthew Dobbertin, Boys Town National Research Hospital
  Non-Presenting Author

• Karina S. Blair, Boys Town National Research Hospital
  Non-Presenting Author

• Harma Meffert, Boys Town National Research Hospital
  Non-Presenting Author

• R. James Blair, Boys Town National Research Hospital
  Non-Presenting Author