Powley, T. L. | Search bioRxiv

bioRxiv2018

Vagus Nerve Stimulation Promotes Gastric Emptying by Increasing Pyloric Opening Measured with Magnetic Resonance Imaging

BackgroundVagus nerve stimulation (VNS) is an emerging electroceutical therapy for remedying gastric disorders that are poorly managed by pharmacological treatments and/or dietary changes. Such therapy seems promising since the vagovagal neurocircuitry controlling the enteric nervous system strongly influences gastric functions.\n\nMethodsHere, the modulatory effects of left cervical VNS on gastric emptying in rats was quantified using a 1) feeding protocol in which the animal voluntarily consumed a post-fast, gadolinium-labeled meal and 2) newly developed, robust, sensitive and non-invasive imaging strategy to measure antral motility, pyloric activity and gastric emptying based on contrast-enhanced magnetic resonance imaging (MRI) and computer-assisted image processing pipelines.\n\nKey ResultsVNS significantly accelerated gastric emptying (control vs. VNS: 24.9{+/-}3.5% vs. 40.7{+/-}3.9% of meal emptied per 4hrs, p<0.05). This effect resulted from a greater relaxation of the pyloric sphincter (control vs. VNS: 1.4{+/-}0.2 vs. 2.5{+/-}0.5 mm2 cross-sectional area of lumen, p<0.05), without notable changes in antral contraction amplitude (control vs. VNS: 30.6{+/-}3.0% vs. 32.5{+/-}3.0% occlusion), peristaltic velocity (control vs. VNS: 0.67{+/-}0.03 vs. 0.67{+/-}0.03 mm/s), or frequency (control vs. VNS: 6.3{+/-}0.1 vs. 6.4{+/-}0.2 cpm). The degree to which VNS relaxed the pylorus positively correlated with gastric emptying rate (r = 0.5465, p<0.01).\n\nConclusions & InferencesThe MRI protocol employed in this study is expected to enable advanced preclinical studies to understand stomach pathophysiology and its therapeutics. Results from this study suggest an electroceutical treatment approach for gastric emptying disorders using cervical VNS to control the degree of pyloric sphincter relaxation.\n\nKey PointsO_LIVagus nerve stimulation is emerging as a new electroceutical therapy for treating gastric disorders. However, its underlying mechanism(s) and therapeutic effect(s) remain incompletely understood.\nC_LIO_LIVagus nerve stimulation significantly accelerated gastric emptying by promoting the relaxation of the pyloric sphincter.\nC_LIO_LIMRI offers high spatial and temporal resolution to non-invasively characterize gastric motility and physiology in preclinical animal models.\nC_LI

bioengineering↗

bioRxiv2017

Vagal Nerve Stimulation Triggers Wide-Spread Evoked Responses and Changes in Large-Scale Functional Connectivity in Rat Brains

Vagus nerve stimulation (VNS) is a therapy for epilepsy and depression. However, its efficacy varies and its mechanism remains unclear. Prior studies have used functional magnetic resonance imaging (fMRI) to map brain activations with VNS in human brains, but have reported inconsistent findings. The source of inconsistency is likely attributable to the complex temporal characteristics of VNS-evoked fMRI responses that cannot be fully explained by simplified response models in the conventional model-based analysis for activation mapping. To address this issue, we acquired 7-Tesla blood oxygenation level dependent fMRI data from anesthetized Sprague-Dawley rats receiving electrical stimulation at the left cervical vagus nerve. Using spatially independent component analysis, we identified 20 functional brain networks and detected the network-wise activations with VNS in a data-driven manner. Our results showed that VNS activated 15 out of 20 brain networks, and the activated regions covered >76% of the brain volume. The time course of the evoked response was complex and distinct across regions and networks. In addition, VNS altered the strengths and patterns of correlations among brain networks relative to those in the resting state. The most notable changes in network-network interactions were related to the limbic system. Together, such profound and widespread effects of VNS may underlie its unique potential for a wide range of therapeutics to relieve central or peripheral conditions.

neuroscience↗