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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; \u0394<jats:italic>t<\/jats:italic><jats:sub>0<\/jats:sub>), and amygdala context-dependent connectivity during the dot-probe task. Our transdiagnostic sample, enriched for irritability, included 351 youth (ages 8\u201318; <jats:italic>M<\/jats:italic>\u2009=\u200912.92 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\u2019s 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, \u0394<jats:italic>t<\/jats:italic><jats:sub>0<\/jats:sub>, all <jats:italic>t<\/jats:italic>s<jats:sub>350<\/jats:sub>\u2009&gt;\u20094.46, <jats:italic>p<\/jats:italic>s\u2009&lt;\u20090.001. In youth with high irritability, elevated \u0394<jats:italic>t<\/jats:italic><jats:sub>0<\/jats:sub> was associated with a weaker amygdala connectivity. In contrast, in youth with low irritability, elevated \u0394<jats:italic>t<\/jats:italic><jats:sub>0<\/jats:sub> 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.<\/jats:p>","DOI":"10.1038\/s41386-022-01307-3","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T01:12:15Z","timestamp":1654045935000},"page":"2283-2291","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Context-dependent amygdala\u2013prefrontal connectivity during the dot-probe task varies by irritability and attention bias to angry faces"],"prefix":"10.1038","volume":"47","author":[{"given":"Reut","family":"Naim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone P.","family":"Haller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia O.","family":"Linke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Jaffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4070-4566","authenticated-orcid":false,"given":"Joel","family":"Stoddard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9938-4048","authenticated-orcid":false,"given":"Anita","family":"Harrewijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Kircanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Bar-Haim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Brotman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"1307_CR1","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.biopsych.2006.08.042","volume":"60","author":"MA Brotman","year":"2006","unstructured":"Brotman MA, Schmajuk M, Rich BA, Dickstein DP, Guyer AE, Costello EJ, et al. 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