Dataset Information

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging.

ABSTRACT:

Background

Vagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS parameters and polarity on postprandial gastric motility remain incompletely characterized.

Methods

In anesthetized rats (N = 3), we applied monophasic electrical stimuli to the left cervical vagus and recorded compound nerve action potential (CNAP) as a measure of nerve response. We evaluated to what extent afferent or efferent pathway could be selectively activated by monophasic VNS. In a different group of rats (N = 13), we fed each rat a gadolinium-labeled meal and scanned the rat stomach with oral contrast-enhanced magnetic resonance imaging (MRI) while the rat was anesthetized. We evaluated the antral and pyloric motility as a function of pulse amplitude (0.13, 0.25, 0.5, 1 mA), width (0.13, 0.25, 0.5 ms), frequency (5, 10 Hz), and polarity of VNS.

Key results

Monophasic VNS activated efferent and afferent pathways with about 67% and 82% selectivity, respectively. Primarily afferent VNS increased antral motility across a wide range of parameters. Primarily efferent VNS induced a significant decrease in antral motility as the stimulus intensity increased (R = -.93, P < .05 for 5 Hz, R = -.85, P < .05 for 10 Hz). The VNS with either polarity tended to promote pyloric motility to a greater extent given increasing stimulus intensity.

Conclusions and inferences

Monophasic VNS biased toward the afferent pathway is potentially more effective for facilitating occlusive contractions than that biased toward the efferent pathway.

SUBMITTER: Lu KH

PROVIDER: S-EPMC7872206 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging.

Lu Kun-Han KH Cao Jiayue J Phillips Robert R Powley Terry L TL Liu Zhongming Z

Neurogastroenterology and motility 20200415 7

<h4>Background</h4>Vagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS parameters and polarity on postprandial gastric motility remain incompletely characterized.<h4>Methods</h4>In anesthetized rats (N = 3), we applied monophasic electrical stimuli to the left cervical vagus and recorded compound nerve action potential (CNAP) as a measure of nerve response. We evaluated to what exten ...[more]

PMID: 32297404

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Project description:BackgroundAutonomic nerve stimulation is used as a treatment for a growing number of diseases. We have previously demonstrated that application of efferent vagus nerve stimulation (eVNS) has promising glucose lowering effects in a rat model of type 2 diabetes. This paradigm combines high frequency pulsatile stimulation to block nerve activation in the afferent direction with low frequency stimulation to activate the efferent nerve section. In this study we explored the effects of the parameters for nerve blocking on the ability to inhibit nerve activation in the afferent direction. The overarching aim is to establish a blocking stimulation strategy that could be applied using commercially available implantable pulse generators used in the clinic.MethodsMale rats (n = 20) had the anterior abdominal vagus nerve implanted with a multi-electrode cuff. Evoked compound action potentials (ECAP) were recorded at the proximal end of the electrode cuff. The efficacy of high frequency stimulation to block the afferent ECAP was assessed by changes in the threshold and saturation level of the response. Blocking frequency and duty cycle of the blocking pulses were varied while maintaining a constant 4 mA current amplitude.ResultsDuring application of blocking at lower frequencies (≤ 4 kHz), the ECAP threshold increased (ANOVA, p < 0.001) and saturation level decreased (p < 0.001). Application of higher duty cycles (> 70%) led to an increase in evoked neural response threshold (p < 0.001) and a decrease in saturation level (p < 0.001). During the application of a constant pulse width and frequency (1 or 1.6 kHz, > 70% duty cycle), the charge delivered per pulse had a significant influence on the magnitude of the block (ANOVA, p = 0.003), and was focal (< 2 mm range).ConclusionsThis study has determined the range of frequencies, duty cycles and currents of high frequency stimulation that generate an efficacious, focal axonal block of a predominantly C-fiber tract. These findings could have potential application for the treatment of type 2 diabetes.

Project description:The assessment of gastric emptying and motility in humans and animals typically requires radioactive imaging or invasive measurements. Here, we developed a robust strategy to image and characterize gastric emptying and motility in rats based on contrast-enhanced magnetic resonance imaging (MRI) and computer-assisted image processing. The animals were trained to naturally consume a gadolinium-labeled dietgel while bypassing any need for oral gavage. Following this test meal, the animals were scanned under low-dose anesthesia for high-resolution T1-weighted MRI in 7 Tesla, visualizing the time-varying distribution of the meal with greatly enhanced contrast against non-gastrointestinal (GI) tissues. Such contrast-enhanced images not only depicted the gastric anatomy, but also captured and quantified stomach emptying, intestinal filling, antral contraction, and intestinal absorption with fully automated image processing. Over four postingestion hours, the stomach emptied by 27%, largely attributed to the emptying of the forestomach rather than the corpus and the antrum, and most notable during the first 30 min. Stomach emptying was accompanied by intestinal filling for the first 2 h, whereas afterward intestinal absorption was observable as cumulative contrast enhancement in the renal medulla. The antral contraction was captured as a peristaltic wave propagating from the proximal to distal antrum. The frequency, velocity, and amplitude of the antral contraction were on average 6.34 ± 0.07 contractions per minute, 0.67 ± 0.01 mm/s, and 30.58 ± 1.03%, respectively. These results demonstrate an optimized MRI-based strategy to assess gastric emptying and motility in healthy rats, paving the way for using this technique to understand GI diseases, or test new therapeutics in rat models.The assessment of gastric emptying and motility in humans and animals typically requires radioactive imaging or invasive measurements. Here, we developed a robust strategy to image and characterize gastric emptying and motility in rats based on contrast-enhanced magnetic resonance imaging (MRI) and computer-assisted image processing. The animals were trained to naturally consume a gadolinium-labeled dietgel while bypassing any need for oral gavage. Following this test meal, the animals were scanned under low-dose anesthesia for high-resolution T1-weighted MRI in 7 Tesla, visualizing the time-varying distribution of the meal with greatly enhanced contrast against non-gastrointestinal (GI) tissues. Such contrast-enhanced images not only depicted the gastric anatomy, but also captured and quantified stomach emptying, intestinal filling, antral contraction, and intestinal absorption with fully automated image processing. Over four postingestion hours, the stomach emptied by 27%, largely attributed to the emptying of the forestomach rather than the corpus and the antrum, and most notable during the first 30 min. Stomach emptying was accompanied by intestinal filling for the first 2 h, whereas afterward intestinal absorption was observable as cumulative contrast enhancement in the renal medulla. The antral contraction was captured as a peristaltic wave propagating from the proximal to distal antrum. The frequency, velocity, and amplitude of the antral contraction were on average 6.34 ± 0.07 contractions per minute, 0.67 ± 0.01 mm/s, and 30.58 ± 1.03%, respectively. These results demonstrate an optimized MRI-based strategy to assess gastric emptying and motility in healthy rats, paving the way for using this technique to understand GI diseases, or test new therapeutics in rat models.

Project description:Background:Electrical stimulation of peripheral nerves is a widely used technique to treat a variety of conditions including chronic pain, motor impairment, headaches, and epilepsy. Nerve stimulation to achieve efficacious symptomatic relief depends on the proper selection of electrical stimulation parameters to recruit the appropriate fibers within a nerve. Recently, electrical stimulation of the vagus nerve has shown promise for controlling inflammation and clinical trials have demonstrated efficacy for the treatment of inflammatory disorders. This application of vagus nerve stimulation activates the inflammatory reflex, reducing levels of inflammatory cytokines during inflammation. Methods:Here, we wanted to test whether altering the parameters of electrical vagus nerve stimulation would change circulating cytokine levels of normal healthy animals in the absence of increased inflammation. To examine this, we systematically tested a set of electrical stimulation parameters and measured serum cytokine levels in healthy mice. Results:Surprisingly, we found that specific combinations of pulse width, pulse amplitude, and frequency produced significant increases of the pro-inflammatory cytokine tumor necrosis factor (TNF), while other parameters selectively lowered serum TNF levels, as compared to sham-stimulated mice. In addition, serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) were significantly increased by select parameters of electrical stimulation but remained unchanged with others. Conclusions:These results indicate that electrical stimulation parameter selection is critically important for the modulation of cytokines via the cervical vagus nerve and that specific cytokines can be increased by electrical stimulation in the absence of inflammation. As the next generation of bioelectronic therapies and devices are developed to capitalize on the neural regulation of inflammation, the selection of nerve stimulation parameters will be a critically important variable for achieving cytokine-specific changes.

Project description:Introduction: VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiseizure effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. Aim: To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractory epilepsy treated by vagus nerve stimulation (VNS), between VNS-stimulated "ON" and nonstimulated "OFF" periods and between responder (R) and nonresponder (NR) patients. Methods: Scalp-EEG was performed for 35 patients treated by VNS, using 21 channels and 2 additional electrodes on the neck to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of ∼50% was documented. We analyzed the synchronization in EEG time series during "ON" and "OFF" periods of stimulation, using average phase lag index (PLI) in signal space and phase-locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and nonresponder patients. Results: Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were R and 15 were NR. For responder patients, PLI during ON periods was significantly lower than that during OFF periods in delta (p = 0.009), theta (p = 0.02), and beta (p = 0.04) frequency bands. For nonresponder patients, there were no significant differences between ON and OFF periods. Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta (p = 0.02), theta (p = 0.04), and beta (p = 0.03) frequency bands. Our results were confirmed using PLV in theta band (p < 0.05). No significant differences in MST were observed between R and NR patients. Conclusion: The correlation between VNS-induced interictal EEG time-series desynchronization and decrease in seizure frequency suggested that VNS therapeutic impact might be related to changes in interictal functional connectivity. Impact statement Electroencephalography (EEG) desynchronization has been proposed to be a mechanism for antiepileptic effect of vagus nerve stimulation (VNS). We measured interictal EEG time-series synchronization during stimulated (ON) and nonstimulated (OFF) periods in epileptic patients treated by VNS. Phase lag index differences between ON and OFF periods were measured in delta, theta, and beta bands only in responder patients. To our knowledge, our study is the first to statistically correlate interictal cortical desynchronization during ON periods with reduction in seizure frequency. Our result supports the hypothesis that the antiseizure effect of VNS is mediated by cortical desynchronization.

Dataset Information

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging.

Background

Methods

Key results

Conclusions and inferences

Publications

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging.

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