Context-dependent amygdala-prefrontal connectivity during the dot-probe task varies by irritability and attention bias to angry faces

Abstract

Irritability, defined as proneness to anger, is among the most common reasons youth are seen for psychiatric care. Youth with irritability demonstrate aberrant processing of anger-related stimuli; however, the neural mechanisms remain unknown. We applied a drift-diffusion model (DDM), a computational tool, to derive a latent behavioral metric of attentional bias to angry faces in youth with varying levels of irritability during functional magnetic resonance imaging (fMRI). We examined associations among irritability, task behavior using a DDM-based index for preferential allocation of attention to angry faces (i.e., extra-decisional time bias; Δt₀), and amygdala context-dependent connectivity during the dot-probe task. Our transdiagnostic sample, enriched for irritability, included 351 youth (ages 8-18; M = 12.92 years, 51% male, with primary diagnoses of either attention deficit/hyperactivity disorder [ADHD], disruptive mood dysregulation disorder [DMDD], an anxiety disorder, or healthy controls). Models accounted for age, sex, in-scanner motion, and co-occurring symptoms of anxiety. Youth and parents rated youth's irritability using the Affective Reactivity Index. An fMRI dot-probe task was used to assess attention orienting to angry faces. In the angry-incongruent vs. angry-congruent contrast, amygdala connectivity with the bilateral inferior frontal gyrus (IFG), insula, caudate, and thalamus/pulvinar was modulated by irritability level and attention bias to angry faces, Δt₀, all ts₃₅₀ > 4.46, ps < 0.001. In youth with high irritability, elevated Δt₀ was associated with a weaker amygdala connectivity. In contrast, in youth with low irritability, elevated Δt₀ was associated with stronger connectivity in those regions. No main effect emerged for irritability. As irritability is associated with reactive aggression, these results suggest a potential neural regulatory deficit in irritable youth who have elevated attention bias to angry cues.