Xiaokai Wang

The default mode network (DMN) is central to cognition. Consistent across species, functional connectivity (FC) of DMN exhibits partly similar patterns across brain states, including wakefulness, sleep, sedated or anesthetized states. Regions in DMN are also involved in regulating visceral organs. It is likely that DMN facilitates visceral physiology to maintain homeostasis in states of unconsciousness. However, the evidence for the association between autonomic function and DMN is sparse and piecemeal. Here, we use fMRI in rat models to investigate how vagal nerve de-innervation and stimulation affect the DMN and its interaction with other regions related to autonomic function.

PurposeMagnetic resonance imaging (MRI) of the gastrointestinal (GI) tract is an emerging technique for non‐invasive assessment of gastric emptying and motility in animals and humans. However, addition of MRI contrast agents to the test meal is often required to produce high luminal contrast to facilitate image analysis. Here, we reported a recipe of a test meal that is all natural (e.g. gadolinium‐free) and safe for humans. The ingredients of the test meal all contain relatively high concentration of manganese, which allow the lumen of the GI tract to be visible inside MRI. To capture gastric emptying and motility simultaneously, we have developed a dynamic 3D imaging protocol with high spatial and temporal resolution and an image segmentation and analysis algorithm.MethodSix healthy volunteers (3 woman; age 24–31) participated in this study. All subjects were asked to fast for 12 hours. Subjects were scanned using a 3T Siemens Prisma MRI scanner using an 18‐channel body coil and a 32‐channel spine coil. Prior to meal consumption, pre‐prandial gastric volume was quantified using a 3D true fast imaging (TRUFI) with steady‐state free precession sequence under free breathing. Then the subjects were instructed to ingest 350 ml of a semi‐solid test meal (263kcal) that contains blended natural foods (i.e. pineapple, banana, blueberry, firm tofu) with a relatively high concentration of manganese. Post‐meal MRI scans were performed using a 3D Spoiled Gradient Echo Variant (VIBE) sequence under gentle breaths over a 90‐minute time course. Post‐prandial gastric volumes, as well as antral contraction frequency and amplitude of the peristaltic wave, were quantified from the dynamic 3D MRI images using a custom‐built image processing pipeline.ResultsPre‐prandial gastric volume was measured prior to test meal consumption (30.98±12.29 mL). After the subjects consumed the test meal, the presence of manganese in the meal enhanced the contrast of the gastric lumen (Fig. 1). The imaging protocol collected fast real‐time MRI scans of the stomach processing and emptying of a meal and the algorithms quantified gastric motility and emptying rate. The stomach volume decreased at a rate of 1.58±0.50 mL/min, mainly attributed to volume decrease in the fundus and the corpus (1.31±0.53 mL/min) than in the antrum (0.28±0.15 mL/min). The frequency of gastric contractions was 2.79±0.17 cycles/min, which was in line with the frequency of gastric slow wave in humans. The displacement of the luminal wall (i.e. contraction amplitude) was greater at the antrum (7.42±1.39 mm) than at the fundus and the corpus (4.52±0.25 mm), as illustrated in Fig. 2.ConclusionHere, we developed a contrast‐enhanced gastric MRI protocol to non‐invasively monitor gastric emptying and motility in humans. Such experimental protocol was further empowered by advanced image analysis to enable comprehensive assessment of gastric functions and physiology. In summary, the proposed method may become a reliable standard to guide diagnosis and treatment of gastric disorders in humans.Support or Funding InformationNIH SPARC OT2OD023847Example gastric MRI images of the stomach distended with the test meal. The contrast of the gastric lumen was significantly enhanced due to the presence of manganese in the meal.Figure 1Mapping amplitude of gastric contractions on the luminal wall. The displacement of the luminal wall was greatest at the antrum, followed by the corpus, and smallest at the fundus.Figure 2

The common occurrence of gastric disorders, the accelerating emphasis on the role of the gut‐brain axis, and development of realistic, predictive models of gastric function, all place emphasis on increasing understanding of the stomach and its control. However, the ways that regions of the stomach have been described anatomically, physiologically, and histologically do not align well. Mammalian single compartment stomachs can be considered as having four anatomical regions fundus, corpus, antrum, and pyloric sphincter. Functional regions are the proximal stomach, primarily concerned with adjusting gastric volume, the distal stomach, primarily involved in churning and propelling the content, and the pyloric sphincter that regulates passage of chyme into the duodenum. The proximal stomach extends from the dome of the fundus to a circumferential band where propulsive waves commence (slow waves of the pacemaker region), and the distal stomach consists of the pacemaker region and the mor...

The strengths, directions and coupling of the movements of the stomach depend on the organisation of its musculature. Although the rat has been used as a model species to study gastric function, there is no detailed, quantitative study of the arrangement of the gastric muscles in rat. Here we provide a descriptive and quantitative account, and compare it with human gastric anatomy. The rat stomach has three components of the muscularis externa, a longitudinal coat, a circular coat and an internal oblique (sling) muscle in the region of the gastro–oesophageal junction. These layers are similar to human. Unlike human, the rat stomach is also equipped with paired muscular oesophago‐pyloric ligaments that lie external to the longitudinal muscle. There is a prominent muscularis mucosae throughout the stomach and strands of smooth muscle occur in the mucosa, between the glands of the corpus and antrum. The striated muscle of the oesophageal wall reaches to the stomach, unlike the human, i...

PurposeThe gut communicates with the brain, allowing the gastrointestinal state to influence cognition and emotion and vice versa. In the resting state, gastric electrical activity has been shown to be synchronized with the blood‐oxygen‐level‐dependent (BOLD) signal in the so‐called gastric network in humans [1]. However, the finding has been rarely replicated. Here, we explored the gut‐brain synchrony in rats. Whole‐brain functional magnetic resonance imaging (fMRI) was acquired simultaneously with electrogastrogram (EGG) recording. Cross‐correlation between EGG and BOLD signals was used to map resting state networks influenced by gastric activity.MethodBrain fMRI was performed on three SD rats together with multi‐channel EGG recording. Each rat was trained to consume diet gel enriched with Gadolinium contrast media. Before the experiment, the rat was fed with 5g diet gel. After the feeding, the animal was anesthetized with continuous dexmedetomidine and isoflurane. The multi‐chann...

Gastrointestinal magnetic resonance imaging (MRI) provides rich spatiotemporal data about the volume and movement of the food inside the stomach, but does not directly report on the muscular activity of the stomach itself. Here we describe a novel approach to characterize the motility of the stomach wall that drives the volumetric changes of the gastric content. In this approach, a surface template was used as a deformable model of the stomach wall. A neural ordinary differential equation (ODE) was optimized to model a diffeomorphic flow that ascribed the deformation of the stomach wall to a continuous biomedical process. Driven by this diffeomorphic flow, the surface template of the stomach progressively changes its shape over time or between conditions, while preserving its topology and manifoldness. We tested this approach with MRI data collected from 10 Sprague Dawley rats under a lightly anesthetized condition. Our proposed approach allowed us to characterize gastric anatomy an...

Interactions between the brain and the stomach shape both cognitive and digestive functions. Recent human studies report spontaneous synchronization between brain activity and gastric slow waves in the resting state. However, this finding has not been replicated in any animal models. The neural pathways underlying this apparent stomach-brain synchrony is also unclear. Here, we performed functional magnetic resonance imaging while simultaneously recording body-surface gastric slow waves from anesthetized rats in the fasting vs. postprandial conditions and performed a bilateral cervical vagotomy to assess the role of the vagus nerve. The coherence between brain fMRI signals and gastric slow waves was found in a distributed “gastric network”, including subcortical and cortical regions in the sensory, motor, and limbic systems. The stomach-brain coherence was largely reduced by the bilateral vagotomy and was different between the fasting and fed states. These findings suggest that the v...

BackgroundTime-sequenced magnetic resonance imaging (MRI) of the stomach is an emerging technique for non-invasive assessment of gastric emptying and motility. However, an automated and systematic image processing pipeline for analyzing dynamic 3D (i.e., 4D) gastric MRI data is not yet available. This study introduces an MRI protocol for imaging the stomach with high spatiotemporal isotropic resolution and provides an integrated pipeline for assessing gastric emptying and motility simultaneously.MethodsDiet contrast-enhanced MRI images were acquired from seventeen healthy humans after they consumed a naturalistic contrast meal. An automated image processing pipeline was developed to correct for respiratory motion, to segment and compartmentalize the lumen-enhanced stomach, to quantify total gastric and compartmental emptying, and to compute and visualize gastric motility on the surface of the stomach.Key ResultsThe gastric segmentation reached an accuracy of 91.10±0.43% with the Typ...

Gastric electrical stimulation (GES) is a bioelectric intervention for gastroparesis, obesity, and other functional gastrointestinal disorders. In a potential mechanism of action, GES activates the nerve endings of vagal afferent neurons and induces the vago-vagal reflex through the nucleus tractus solitarius (NTS) in the brainstem. However, it is unclear where and how to stimulate in order to optimize the vagal afferent responses. To address this question with electrophysiology in rats, we applied mild electrical currents to two serosal targets on the distal forestomach with dense distributions of vagal intramuscular arrays that innervated the circular and longitudinal smooth muscle layers. During stimulation, we recorded single and multi-unit responses from gastric neurons in NTS and evaluated how the recorded responses depended on the stimulus orientation and amplitude. We found that NTS responses were highly selective to the stimulus orientation for a range of stimulus amplitude...