<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Increasing brain imaging studies have emphasized the role of regional brain activity abnormalities in functional dyspepsia (<jats:styled-content style="fixed-case">FD</jats:styled-content>) during the resting state. The goal of this study was to investigate the default mode network (<jats:styled-content style="fixed-case">DMN</jats:styled-content>) in <jats:styled-content style="fixed-case">FD</jats:styled-content> patients and healthy controls (<jats:styled-content style="fixed-case">HC</jats:styled-content>s).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Resting‐state functional magnetic resonance imaging (<jats:styled-content style="fixed-case">fMRI</jats:styled-content>) scanning was carried out on 49 patients and 39 <jats:styled-content style="fixed-case">HC</jats:styled-content>s. Independent component analysis (<jats:styled-content style="fixed-case">ICA</jats:styled-content>) was used to isolate the <jats:styled-content style="fixed-case">DMN</jats:styled-content> in each subject. Group topography of the <jats:styled-content style="fixed-case">DMN</jats:styled-content> was compared to study significant alteration in <jats:styled-content style="fixed-case">FD</jats:styled-content>. A correlation analysis was then performed in the <jats:styled-content style="fixed-case">FD</jats:styled-content> group to investigate the effects of symptom severity and the psychological factors on the <jats:styled-content style="fixed-case">DMN</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Key Results</jats:title><jats:p>Significant spatial differences with the <jats:styled-content style="fixed-case">DMN</jats:styled-content> in <jats:styled-content style="fixed-case">FD</jats:styled-content> patients, compared with <jats:styled-content style="fixed-case">HC</jats:styled-content>s, were mainly found in the dorsomedial prefrontal cortex (dm<jats:styled-content style="fixed-case">PFC</jats:styled-content>), ventromedial prefrontal cortex (vm<jats:styled-content style="fixed-case">PFC</jats:styled-content>), orbitofrontal cortex (<jats:styled-content style="fixed-case">OFC</jats:styled-content>), pregenual anterior cingulate cortex (<jats:styled-content style="fixed-case">pACC</jats:styled-content>), thalamus, parahippocampal gyrus, precuneus, parietal cortex, and temporal pole. Meanwhile, Nepean Dyspepsia Index (<jats:styled-content style="fixed-case">NDI</jats:styled-content>) scores were positively correlated with the <jats:styled-content style="fixed-case">pACC</jats:styled-content>, and was negative correlated with the <jats:styled-content style="fixed-case">OFC</jats:styled-content>. However, both the Self‐Rating Anxiety Scale (<jats:styled-content style="fixed-case">SAS</jats:styled-content>) and Self‐Rating Depression Scale (<jats:styled-content style="fixed-case">SDS</jats:styled-content>) scores were not correlated with any regions of interest showing differences between the <jats:styled-content style="fixed-case">FD</jats:styled-content> patients and the <jats:styled-content style="fixed-case">HC</jats:styled-content>s.</jats:p></jats:sec><jats:sec><jats:title>Conclusions & Inferences</jats:title><jats:p>These findings suggested that the <jats:styled-content style="fixed-case">DMN</jats:styled-content> might indeed undergo dysfunctional changes due to the abnormal persistent activity in <jats:styled-content style="fixed-case">FD</jats:styled-content> patients. To a certain extent, the changes in the <jats:styled-content style="fixed-case">DMN</jats:styled-content> were related to the <jats:styled-content style="fixed-case">FD</jats:styled-content>‐related symptom severity.</jats:p></jats:sec>