{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:42:01Z","timestamp":1768563721972,"version":"3.49.0"},"posted":{"date-parts":[[2023,6,12]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":88,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Hyperarousal symptoms in generalized anxiety disorder (GAD) are often incongruent with the observed physiological state, suggesting that abnormal processing of interoceptive signals is a characteristic feature of the disorder. To examine the neural mechanisms underlying interoceptive dysfunction in GAD, we evaluated whether adrenergic modulation of cardiovascular signaling differentially affects the heartbeat evoked potential (HEP), an electrophysiological marker of cardiac interoception, during concurrent electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) scanning. Intravenous infusions of the peripheral adrenergic agonist isoproterenol (0.5 and 2.0 micrograms, \u03bcg) were administered in a randomized, double-blinded and placebo-controlled fashion to dynamically perturb the cardiovascular system while recording the associated EEG-fMRI responses. During the 0.5 \u03bcg isoproterenol infusion, the GAD group (n=24) exhibited significantly larger changes in HEP amplitude in an opposite direction than the HC group (n=24). In addition, the GAD group showed significantly larger absolute HEP amplitudes than HC during saline infusions, when cardiovascular tone did not increase. No significant group differences in HEP amplitude were identified during the 2.0 \u03bcg isoproterenol infusion. Using analyzable blood oxygenation level dependent fMRI data from participants with concurrent EEG-fMRI data (21 GAD and 21 HC), we found that the aforementioned HEP effects were uncorrelated with fMRI signals in the insula, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, amygdala, and somatosensory cortex, brain regions implicated in cardiac signal processing according to prior fMRI studies. These findings provide additional evidence of dysfunctional cardiac interoception in GAD and identify neural processes at the electrophysiological level that may be independent from blood oxygen level\u2013dependent responses during peripheral adrenergic stimulation.<\/jats:p>","DOI":"10.1101\/2023.06.09.23291166","type":"posted-content","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T14:25:19Z","timestamp":1686579919000},"source":"Crossref","is-referenced-by-count":5,"title":["Heartbeat-evoked neural response abnormalities in generalized anxiety disorder during peripheral adrenergic stimulation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0778-1981","authenticated-orcid":false,"given":"Charles","family":"Verdonk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam R.","family":"Teed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan J.","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0825-3606","authenticated-orcid":false,"given":"Martin P.","family":"Paulus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-8585","authenticated-orcid":false,"given":"Sahib S.","family":"Khalsa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023122619450713000_2023.06.09.23291166v4.1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425787"},{"key":"2023122619450713000_2023.06.09.23291166v4.2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.62.6.593"},{"key":"2023122619450713000_2023.06.09.23291166v4.3","unstructured":"World Health Organization: ICD-11 for Mortality and Morbidity Statistics - 6B00 Generalised anxiety disorder. https:\/\/icd.who.int\/browse11\/l-m\/en#\/ http:\/\/id.who.int\/icd\/entity\/1712535455 (2022). 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