SPARC: Brain‐stomach Synchrony Observed with Functional Magnetic Resonance Imaging and Electrogastrogram in Rats
Authors: Cao Jiayue , Wang Xiaokai , Lu Kun-Han , Tan Zhenjun , Phillips Robert , Jaffey Deborah , Wo John , Mosier Kristine , Powley Terry , Liu Zhongming 
Published: April 2020

Purpose

The 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.

Method

Brain 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‐channel EGG signal was recorded using an electrophysiological recording system (Tucker Davis Technologies Inc.) together with fMRI scans using a 7‐tesla small‐animal MRI system (BioSpec 70/30, Bruker). The principal component analysis was applied to EGG signals. The correlation between the voxel‐wise fMRI signal and the component‐wise EGG signal was calculated, yielding multiple gut‐associated brain networks. The voxel‐wise fMRI signal was also modeled as a linear combination of EGG component time series with varying time shifts.

Results

FMRI was acquired simultaneously with the EGG recording ( Fig.
1A). EGG was denoised and cross‐correlated with the BOLD activity in every voxel to map an EGG‐correlated network (or the gastric network) ( Fig.
1C). The BOLD signal was averaged across voxels in the gastric network. The resulting network‐wide signal was found to be phase‐locked to EGG with a time delay ( Fig.
1B). Accounting for the delay variable across voxels, we mapped an even broader network phase‐locked with EGG ( Fig.
2A). Different EGG‐coupled regions were found to lag behind EGG by different times, ranging from 4 to 12 seconds ( Fig.
2B & C). From the EGG‐coupled BOLD response, the visual and auditory cortex had a relatively longer delay, whereas the somatosensory and anterior cingulate cortex had a shorter delay. The cingulate cortex showed a complex response pattern, likely implying multiple functional roles with respect to the gut.

Conclusion

In rats, brain activity is intrinsically synchronized with gastric activity at a specific resting state network. In this network, different brain regions are time‐locked to gastric activity with varying time delays. Speculatively, the pattern of time delay may reflect how gastric information propagates through a cascade of brain regions for sequential processing.

Support or Funding Information

This study was funded by National Institutes of Health’s SPARC ‐ Stimulating Peripheral Activity to Relieve Conditions ‐ program (OT2OD023847).

Simultaneous EGG and brain fMRI recording. (A) shows the layout of the 32‐channel electrode array for EGG recording. (B) are examples of EGG and fMRI time series. (C) shows an example of the EGG correlation map. The correlation between EGG and fMRI time series is color‐coded.

Figure 1

The EGG network considering the phase delays between EGG and fMRI signal. (A) is a summary of the EGG network. The color represents the F statistic of the multiple linear regression. (B) selects six voxels in the EGG network. The curve shows the relation between the F statistic and EGG‐fMRI delays for the selected voxels, which are marked with blue box in (A). (C) is the phase delay map that delineates the phase differences between EGG and fMRI time series.

Figure 2