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

Reut Naim, Simone P Haller, Julia O Linke, Allison Jaffe, Joel Stoddard, Matt Jones, Anita Harrewijn, Katharina Kircanski, Yair Bar-Haim, Melissa A Brotman

Research output: Contribution to journalArticleAcademicpeer-review

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; Δt 0), 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, Δt 0, all ts 350 > 4.46, ps < 0.001. In youth with high irritability, elevated Δt 0 was associated with a weaker amygdala connectivity. In contrast, in youth with low irritability, elevated Δt 0 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.

Original languageEnglish
Pages (from-to)2283-2291
Number of pages9
JournalNeuropsychopharmacology
Volume47
Issue number13
Early online date1 Jun 2022
DOIs
Publication statusPublished - 1 Jun 2022
Externally publishedYes

Bibliographical note

Funding Information:
The authors appreciate the role of Drs. Ellen Leibenluft and Daniel S. Pine in early consultation and discussion about the findings and potential implications. The authors would like to thank the patients and families for their time and participation. This work was supported by the Intramural Research Program (IRP) of the National Institute of Mental Health, National Institutes of Health (NIMH/NIH), ZIAMH002781 (Pine), ZIAMH002786 (Leibenluft), ZIAMH002778 (Leibenluft), and conducted under NIH Clinical Study Protocols 01-M-0192 and M-00-M-0021 [ClinicalTrials.gov identifiers: NCT00018057 (Pine) and NCT00025935 (Brotman)]. This body had no role in the study design, writing the manuscript, or the decision to submit the paper for publication. This research received no specific external grant from any funding agency, commercial or not-for-profit sectors.

Publisher Copyright:
© 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

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