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We conducted a preregistered functional neuroimaging study of 46 individuals with anxiety, depression, and\/or eating disorders (ADE) and 46 propensity-matched healthy comparisons (HC), comparing their neural activity across two interoceptive tasks differentially recruiting top-down or bottom-up processing within the same scan session. During an interoceptive attention task, top-down attention was voluntarily directed towards cardiorespiratory or visual signals. In contrast, during an interoceptive perturbation task, intravenous infusions of isoproterenol (a peripherally-acting beta-adrenergic receptor agonist) were administered in a double-blinded and placebo-controlled fashion to drive bottom-up cardiorespiratory sensations. Across both tasks, neural activation converged upon the insular cortex, localizing within the granular and ventral dysgranular subregions bilaterally. However, contrasting hemispheric differences emerged, with the ADE group exhibiting (relative to HCs) an asymmetric pattern of overlap in the left insula, with increased or decreased proportions of co-activated voxels within the left or right dysgranular insula, respectively. The ADE group also showed less agranular anterior insula activation during periods of bodily uncertainty (i.e. when anticipating possible isoproterenol-induced changes that never arrived). Finally, post-task changes in insula functional connectivity were associated with anxiety and depression severity. These findings confirm the dysgranular mid-insula as a key cortical interface where attention and prediction meet real-time bodily inputs, especially during heightened awareness of interoceptive states. Furthermore, the dysgranular mid-insula may indeed be a \u2018locus of disruption\u2019 for psychiatric disorders.<\/jats:p>","DOI":"10.7554\/elife.92820","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T06:25:08Z","timestamp":1707373508000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.92820","source":"Crossref","is-referenced-by-count":8,"title":["Hemispheric divergence of interoceptive processing across psychiatric disorders"],"prefix":"10.7554","volume":"13","author":[{"given":"Emily M","family":"Adamic","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05e6pjy56","id-type":"ROR","asserted-by":"publisher"}],"name":"Laureate Institute for Brain Research","place":["Tulsa, United States"]},{"id":[{"id":"https:\/\/ror.org\/04wn28048","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Sciences, University of Tulsa","place":["Tulsa, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Adam R","family":"Teed","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05e6pjy56","id-type":"ROR","asserted-by":"publisher"}],"name":"Laureate Institute for Brain Research","place":["Tulsa, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jason","family":"Avery","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Brain and Cognition, National Institute of Mental Health","place":["Bethesda, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Feliberto","family":"de la Cruz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035rzkx15","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory for Autonomic Neuroscience, Imaging, and Cognition (LANIC), Department of Psychosomatic Medicine and Psychotherapy, Jena University Hospital","place":["Jena, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-8585","authenticated-orcid":true,"given":"Sahib","family":"Khalsa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05e6pjy56","id-type":"ROR","asserted-by":"publisher"}],"name":"Laureate Institute for Brain Research","place":["Tulsa, United States"]},{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles","place":["Los Angeles, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.17605\/OSF.IO\/6NXA3","type":"journal-article","article-title":"Convergence between goal-directed and stimulus-driven streams of cardiorespiratory interoception","volume":"25","author":"Adamic","year":"2021","journal-title":"Osf"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.cortex.2016.12.019","type":"journal-article","article-title":"Convergence of interoception, emotion, and social cognition: A twofold FMRI meta-analysis and lesion approach","volume":"88","author":"Adolfi","year":"2017","journal-title":"Cortex; 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