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We have previously shown that gastroesophageal reflux disease (<jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content>) patients have increased insular cortex activity during esophageal stimulation, suggesting a sensitized esophago\u2010cortical neuraxis. However, information regarding the functional connectivity (<jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content>) of the insula during visceral stimulation is lacking. The primary aim of this study was to investigate the <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content> of insular subregions during esophageal acid stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Functional imaging data were obtained from 12 <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> patients and 14 healthy subjects during four steady state conditions: (i) presence of transnasal esophageal catheter (pre\u2010infusion); (ii) neutral solution; (iii) acid infusion; (iv) presence of transnasal esophageal catheter following infusions (post\u2010infusion). The insula was parcellated into six regions of interest. <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content> maps between each insular <jats:styled-content style=\"fixed-case\">ROI<\/jats:styled-content> and interoceptive regions were created. Differences in <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content> between <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> patients and healthy subjects were determined across the 4 study conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>All <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> patients experienced heartburn during and after esophageal acidification. Significant differences between <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> patients and healthy subjects were seen in: (i) insula\u2010thalamic <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content> (neutral solution infusion, acid infusion, post\u2010infusion); (ii) insula\u2010amygdala <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content> (acid infusion, post\u2010infusion); (iii) insula\u2010hippocampus and insula\u2010cingulate <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content> (post\u2010infusion).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Esophageal stimulation in <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> patients revealed significant insular cortex <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content> differences with regions involved in viscerosensation and interoception. The results of our study provide further evidence that the insula, located at the transition of afferent physiologic information to human feelings, is essential for both visceral homeostasis and the experience of heartburn in <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12464","type":"journal-article","created":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T06:06:14Z","timestamp":1415081174000},"page":"201-211","source":"Crossref","is-referenced-by-count":8,"title":["Esophageal acid stimulation alters insular cortex functional connectivity in gastroesophageal reflux disease"],"prefix":"10.1111","volume":"27","author":[{"given":"R. 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