Interplay of spinal and vagal pathways on esophageal acid-related anterior cingulate cortex functional networks in rats

Abstract

Esophageal acid sensory signals are transmitted by both vagal and spinal pathways to the cerebral cortex. The influence and interplay of these pathways on esophageal acid-related functional connectivity has been elusive. Our aim was to evaluate the esophageal acid exposure-related effect on the anterior cingulate cortex (ACC) functional connectivity networks using functional MRI-guided functional connectivity MRI (fcMRI) analysis. We studied six Sprague-Dawley rats for fcMRI experiments under dexmedetomidine hydrochloride anesthesia. Each rat was scanned for 6 min before and after esophageal hydrochloric acid infusion (0.1 N, 0.2 ml/min). The protocol was repeated before and after bilateral cervical vagotomy on the same rat. Seed-based fcMRI analysis was used to examine ACC networks and acid-induced network alterations. Three-factor repeated-measures ANOVA analysis among all four subgroups revealed that the interaction of acid infusion and bilateral vagotomy was mainly detected in the hypothalamus, insula, left secondary somatosensory cortex, left parietal cortex, and right thalamus in the left ACC network. In the right ACC network, this interaction effect was detected in the caudate putamen, insula, motor, primary somatosensory cortex, secondary somatosensory cortex, and thalamic regions. These regions in the ACC networks showed decreased intranetwork connectivity due to acid infusion. However, after bilateral vagotomy, intranetwork connectivity strength inversed and became stronger following postvagotomy acid infusion. Signals transmitted through both the vagal nerve and spinal nerves play a role in esophageal acid-related functional connectivity of the ACC. The vagal signals appear to dampen the acid sensation-related functional connectivity of the ACC networks. NEW & NOTEWORTHY These studies show that esophageal acid-induced brain functional connectivity changes are vagally mediated and suggest that signals transmitted through both the vagal nerve and spinal nerves play a role in esophageal acid-related functional connectivity of the anterior cingulate cortex. This paper focuses on the development of a novel rat functional MRI model fostering improved understanding of acid-related esophageal disorders.

Keywords: cingulate; esophageal acid; functional MRI; vagus.

Fig. 1.

Functional connectivity magnetic resonance imaging (fcMRI) paradigm depicting timing of MRI scanning relative to acid infusion and vagotomy.

Fig. 2.

Seed regions of bilateral anterior cingulate cortex (ACC) identified from functional MRI overlaid on rat anatomic images. Significantly differential clusters (P < 0.05 with correction) between esophageal acid and saline infusion.

Fig. 3.

Main effect of acid infusion on left (L) and right (R) anterior cingulate cortex (ACC) networks (P < 0.05 with correction). Brain regions are overlaid on rat anatomic images. CPU, caudate putamen; S2, secondary somatosensory cortex; INS, insula; HT, hypothalamus; M, motor cortex.

Fig. 4.

Main effect of acid infusion on left (L) and right (R) anterior cingulate cortex (ACC) networks (P < 0.05 with correction). Mean normalized functional connectivity scores ± SE are depicted for each condition.

Fig. 5.

Interaction effect of acid infusion and bilateral vagotomy on left (L) and right (R) anterior cingulate cortex (ACC) networks (P < 0.05 with correction). Brain regions are overlaid on rat anatomic images. S2, secondary somatosensory cortex; INS, insula; HT, hypothalamus; TH, thalamus; PR, parietal cortex; CPU, caudate putamen; S1, primary somatosensory cortex; M, motor cortex.

Fig. 6.

Interaction effect of acid infusion and bilateral vagotomy on the left (L) and right (R) anterior cingulate cortex (ACC) networks (P < 0.05 with correction). Mean normalized functional connectivity scores ± SE are depicted for each condition.

Fig. 7.

Representative figure of the blood oxygenation level-dependent (BOLD) signal time course of the right anterior cingulate cortex seed region and the left thalamus in a single rat depicted for each condition. CC, correlation coefficient.