Dual neurocircuitry dysfunctions in disruptive behavior disorders: emotional responding and response inhibition

Abstract

Background: To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10-18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits.

Method: Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group×emotion by task) was conducted on the BOLD response data.

Results: Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD.

Conclusions: These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology.

Keywords: Amygdala; callous-unemotional trait; disruptive behavior disorder; emotional responding; response inhibition.

Figure 1

Example trial sequences. (a) negative view trial; (b) negative congruent trial; (c) negative incongruent trial.

Figure 2

Regions showing a significant group-by-emotion interaction: (A) lBOLD response data: eft ventromedial prefrontal cortex (coordinates: −4.5, 43.5, −12.5, at =0.005); (B) Parameter estimates for left vmPFC; (C) Negative correlation between symptom severity of callous-unemotional trait measured by the ICU (x-axis) and BOLD response parameter estimates of negative relative to neutral trials (y-axis) in left vmPFC; (D) right amygdala ROI (at p=0.05); (E) Parameter estimates for this region; (gPPI data with right amygdala seed: ); (E) left inferior frontal gyrus (coordinates: −40.5, 40.5, −0.5 at p=0.005) and; (G) Parameter estimates for this region;. Key to Figure 1: Neg: Negative; Neu: Neutral; Pos: Positive; Healthy: healthy youths; LCU: youths with DBD-LCU; HCU: youths with DBD-HCU. * = significant contrasts for interaction variables (p<0.05). The results are showing on the Talairach space.

Figure 3

Regions showing a significant group-by-task interaction: (A) bilateral insula (coordinates: 37.5, −13.5, −6.5; −37.5, 7.5, −0.5 at p=0.005) via Healthy versus DBD ANOVA; (B) Parameter estimates for this region; (C) Negative correlation between ADHD symptom severity measured by Connor parent report scale (x-axis) and BOLD response parameter estimates of congruent relative to view trials (y-axis); (D) left insula (coordinates: −37.5, 7.5, −0.5 at p=0.005) via Healthy vs. DBD-LCU vs. DBD-HCU ANOVA; (E) Parameter estimates for this region. Key to Figure 3: Incong: Incongruent trial; Cong: Congruent trial; View: View trial; Healthy: healthy youths; DBD: youths with DBD; LCU: youths with DBD-LCU; HCU: youths with DBD-HCU. * = significant contracts for interaction variables (p<0.05). The results are showing on the Talairach space.