Cine gastric MRI reveals altered Gut-Brain Axis in Functional Dyspepsia: gastric motility is linked with brainstem-cortical fMRI connectivity

Abstract

Background: Functional dyspepsia (FD) is a disorder of gut-brain interaction, and its putative pathophysiology involves dysregulation of gastric motility and central processing of gastric afference. The vagus nerve modulates gastric peristalsis and carries afferent sensory information to brainstem nuclei, specifically the nucleus tractus solitarii (NTS). Here, we combine MRI assessment of gastric kinematics with measures of NTS functional connectivity to the brain in patients with FD and healthy controls (HC), in order to elucidate how gut-brain axis communication is associated with FD pathophysiology.

Methods: Functional dyspepsia and HC subjects experienced serial gastric MRI and brain fMRI following ingestion of a food-based contrast meal. Gastric function indices estimated from 4D cine MRI data were compared between FD and HC groups using repeated measure ANOVA models, controlling for ingested volume. Brain connectivity of the NTS was contrasted between groups and associated with gastric function indices.

Key results: Propagation velocity of antral peristalsis was significantly lower in FD compared to HC. The brain network defined by NTS connectivity loaded most strongly onto the Default Mode Network, and more strongly onto the Frontoparietal Network in FD. FD also demonstrated higher NTS connectivity to insula, anterior cingulate and prefrontal cortices, and pre-supplementary motor area. NTS connectivity was linked to propagation velocity in HC, but not FD, whereas peristalsis frequency was linked with NTS connectivity in patients with FD.

Conclusions & inferences: Our multi-modal MRI approach revealed lower peristaltic propagation velocity linked to altered brainstem-cortical functional connectivity in patients suffering from FD suggesting specific plasticity in gut-brain communication.

Keywords: MRI; functional dyspepsia; interoception; stomach; vagus nerve.

Figure 1.

Gut and brain MR imaging protocol. Following ingestion of the contrast meal, subjects were positioned supine on the MRI table which was translated to allow for sequential gut (G0–2) and brain (B0–2) MRI, three scans each per body region.

Figure 2.

Calculation of motility indices from cross-sectional areas of antral slices. A cuboid was positioned along the parallel axis of the antrum, and cross-sectional areas were computed at each slice for every acquired imaging timepoint. Peristaltic propagation velocity and frequency were calculated in addition to antral occlusion by tracking the contraction cycles over time and distance along the antrum.

Figure 3.

Patients with FD showed comparable gastric volumetric measurements, but altered antral motility indices relative to healthy controls. A) Patients with FD displayed lower peristaltic propagation velocity and lower antral occlusion compared to healthy controls. No differences were observed in frequency or mean deformation of the antral contractions. B) Total, meal, and air volumes were assessed at each gut imaging timepoint. Patients and controls did not differ in rates of volume change (emptying was consistent across groups), and absolute volumetric differences were driven by differences in ingested volumes. P-values shown represent the main effect of Group in mixed effects models. FD – functional dyspepsia, HC – healthy controls.

Figure 4.

Altered patterns of NTS functional connectivity in patients with FD compared to healthy controls. A) The NTS functional connectivity pattern loaded most strongly onto the default mode network in both groups. Patients with FD displayed higher loading of NTS functional connectivity pattern onto the frontoparietal network compared to healthy controls. B) Seed-voxel whole brain functional connectivity analysis demonstrated greater connectivity between the NTS and the anterior cingulate cortex, pre-supplementary motor area, ventrolateral prefrontal cortex, and anterior insula in patients with FD relative to healthy controls. FD – functional dyspepsia, HC – healthy control, NTS – nucleus tractus solitarii.

Figure 5.

Antral motility indices are correlated with functional connectivity between the NTS and motor and processing regions. In the combined group (FD and HC) sample, peristaltic frequency was correlated to functional connectivity between the NTS and the left vlPFC, preSMA, and left anterior insula. These correlations were significant for a non-combined, FD-alone, group as well (Table 2). Peristaltic propagation velocity was correlated to functional connectivity between the NTS and the left vlPFC and preSMA. The correlation between velocity and NTS / vlPFC connectivity was also significant for a non-combined, HC-alone, group as well. vlPFC – ventrolateral prefrontal cortex, preSMA – pre-supplementary motor area, LaIns – left anterior insula, NTS – nucleus tractus solitarii.