Disrupted intrinsic connectivity of the periaqueductal gray in patients with functional dyspepsia: A resting‐state fMRI study

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Functional dyspepsia (<jats:styled-content style="fixed-case">FD</jats:styled-content>) is a common functional gastrointestinal disorder. Accumulating evidence suggests the crucial role of central nervous system in the development and maintenance of <jats:styled-content style="fixed-case">FD</jats:styled-content>. In particular, periaqueductal gray (<jats:styled-content style="fixed-case">PAG</jats:styled-content>) has demonstrated an important role in modulation of pain and emotion, which may be related to <jats:styled-content style="fixed-case">FD</jats:styled-content>. However, the study of the <jats:styled-content style="fixed-case">PAG</jats:styled-content> in <jats:styled-content style="fixed-case">FD</jats:styled-content> is still limited. This study aimed to assess intrinsic connectivity of the <jats:styled-content style="fixed-case">PAG</jats:styled-content> in <jats:styled-content style="fixed-case">FD</jats:styled-content> patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Resting‐state functional magnetic imaging (<jats:styled-content style="fixed-case">fMRI</jats:styled-content>) data were collected from 66 <jats:styled-content style="fixed-case">FD</jats:styled-content> patients and 42 healthy controls (<jats:styled-content style="fixed-case">HC</jats:styled-content>s). Functional connectivity analysis was performed to investigate the <jats:styled-content style="fixed-case">PAG</jats:styled-content> connectivity pattern differences between the patients and <jats:styled-content style="fixed-case">HC</jats:styled-content>s. We then examined the relationships between functional connectivity within the <jats:styled-content style="fixed-case">PAG</jats:styled-content> networks and <jats:styled-content style="fixed-case">FD</jats:styled-content> symptoms.</jats:p></jats:sec><jats:sec><jats:title>Key Results</jats:title><jats:p>Compared to <jats:styled-content style="fixed-case">HC</jats:styled-content>s, patients had increased <jats:styled-content style="fixed-case">PAG</jats:styled-content> connectivity with the insula, and decreased <jats:styled-content style="fixed-case">PAG</jats:styled-content> connectivity with the orbitofrontal cortex (<jats:styled-content style="fixed-case">OFC</jats:styled-content>), dorsolateral prefrontal cortex (dl<jats:styled-content style="fixed-case">PFC</jats:styled-content>) and hippocampus/parahippocampus (<jats:styled-content style="fixed-case">HIPP</jats:styled-content>/para<jats:styled-content style="fixed-case">HIPP</jats:styled-content>). There were positive correlations between disease duration and <jats:styled-content style="fixed-case">PAG</jats:styled-content> connectivity with the putamen and supplementary motor area (<jats:styled-content style="fixed-case">SMA</jats:styled-content>), and positive correlations between symptom severity and <jats:styled-content style="fixed-case">PAG</jats:styled-content> connectivity with the insula. <jats:styled-content style="fixed-case">FD</jats:styled-content> patients with high level of anxiety and depression had altered <jats:styled-content style="fixed-case">PAG</jats:styled-content> connectivity with the anterior cingulate cortex (<jats:styled-content style="fixed-case">ACC</jats:styled-content>), precuneus, dl<jats:styled-content style="fixed-case">PFC</jats:styled-content> and caudate, compared to other patients.</jats:p></jats:sec><jats:sec><jats:title>Conclusions & Inferences</jats:title><jats:p>These findings indicate that abnormal intrinsic network of the <jats:styled-content style="fixed-case">PAG</jats:styled-content> might be associated with abnormality of pain processing and disruption of emotion processing in <jats:styled-content style="fixed-case">FD</jats:styled-content> patients. Our study further complements neuroimaging findings about <jats:styled-content style="fixed-case">FD</jats:styled-content>.</jats:p></jats:sec>