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

Lu, Kun‐Han; Cao, Jiayue; Oleson, Steven; Ward, Matthew; Powley, Terry L.; Liu, Zhongming

doi:10.1101/253674

Cited by 10 publications

(16 citation statements)

References 47 publications

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“…The Gd-labeled test meal was made of 10g Dietgel mixed with 22.4mg Gd-DTPA powder (#381667, Sigma Aldrich, St. Louis, USA) using a double-boiled liquefying approach. Soon after ingestion, the animal was anesthetized with Isoflurane followed by implantation of a bipolar cuff electrode (Pt/Ir electrode; MicroProbes, Gaithersburg, MD, USA) Lu 8 onto the left cervical vagus nerve with a surgical procedure identical to that described in our previous work 21 . The specification of the bipolar cuff electrode is illustrated in Fig.…”

Section: Animal Preparation and Surgical Implantation Of Stimulating mentioning

confidence: 99%

“…combined afferent and efferent VNS) to the rats in the afferent VNS group, immediately after which afferent VNS was performed. The Lu 10 bidirectional VNS was achieved by delivering rectangular pulses of current in alternating directions between the two electrodes as elaborated elsewhere 21 .…”

Section: Experimental Protocolmentioning

confidence: 99%

“…In this regard, we have recently demonstrated the use of contrast-enhanced magnetic resonance imaging (MRI) to noninvasively monitor gastric emptying and motility in dietgel-fed rats 20 . The imaging capability has also enabled us to validate the efficacy of left cervical VNS for promoting gastric emptying 21 .…”

Section: Introductionmentioning

confidence: 99%

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Differential Effects of Afferent and Efferent Vagus Nerve Stimulation on Gastric Motility Assessed with Magnetic Resonance Imaging

Cao²,

Phillips

et al. 2019

Preprint

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BackgroundVagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the functional impact of different VNS parameters on postprandial gastric motility remains incompletely characterized. Moreover, while most studies focused on stimulating the motor limb (i.e. efferent VNS) of the vagovagal circuitry, the contribution of electrically activating the reflex arc of the circuitry (i.e. afferent VNS) to downstream control of gastric function has seldom been investigated. MethodsHere, we used dynamic gastric magnetic resonance imaging (MRI) to assess antropyloric motility in anesthetized rats during which VNS was applied to the left cervical vagus. The configuration of VNS was varied in terms of directionality (i.e. afferent, efferent or combined afferent and efferent VNS) as well as parameter settings (i.e. pulse amplitude, pulse width, and frequency). The motility measurements were computed using a previously developed computerassisted image processing pipeline. Key ResultsWe found that electrical activation that favored the afferent pathway could promote gastric motility and coordination more effectively than direct activation of the efferent pathway.A reduction in antral contraction amplitude and pyloric tone under high-dose efferent VNS highlighted the inhibitory role of the efferent vagovagal circuitry. Conclusions & InferencesLu 3 This study demonstrated the direct and reflex gastric responses to cervical VNS measured with MRI. Our findings suggest that selective stimulation of vagal afferents is potentially more favorable than stimulation of vagal efferents in facilitating coordinated antropyloric motility. Lu 4Key Points 1. Vagus nerve stimulation is emerging as a new bioelectronic therapy for remedying gastric symptoms. However, the effects of graded VNS settings and directionality preferences of VNS on gastric functions remain incompletely characterized.2. Dynamic gastric MRI revealed that electrical activation of the afferent pathway could promote antropyloric motility more effectively than direct activation of the efferent pathway.3. MRI can noninvasively characterize post-prandial gastric motility with high spatial and temporal resolution that could be used to guide the selection of VNS settings.Lu 5

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Section: Animal Preparation and Surgical Implantation Of Stimulating mentioning

confidence: 99%

Section: Experimental Protocolmentioning

confidence: 99%

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Differential Effects of Afferent and Efferent Vagus Nerve Stimulation on Gastric Motility Assessed with Magnetic Resonance Imaging

Cao²,

Phillips

et al. 2019

Preprint

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“…The gastric MRI data were processed and registered using a custom-built software developed in MATLAB as described else-where [40]. The antral region of the stomach was segmented, and a contraction time series was obtained for every location along the antral axis, through a methodology described in Lu et al [41].…”

Section: Post-processingmentioning

confidence: 99%

“…7a. The cross-sectional area of the distal antrum (lower part of the stomach, adjoining to duodenum) was quantified from the acquired images through the procedure described in an earlier study [45].…”

Section: Gastric Mri and Vagal Nerve Stimulationmentioning

confidence: 99%

MRI Powered and Triggered Current Stimulator for Concurrent Stimulation and MRI

Mandal

Babaria²,

Cao

et al. 2019

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Bioelectric stimulation during concurrent magnetic resonance imaging (MRI) is of interest to basic and translational studies. However, existing stimulation systems often interfere with MRI, are difficult to use or scale up, have limited efficacy, or cause safety concerns. To address these issues, we present a novel device capable of supplying current stimulation synchronized with MRI while being wirelessly powered by the MRI gradient fields. Results from testing it with phantoms and live animals in a 7 Tesla small-animal MRI system suggest that the device is able to harvest up to 72 (or 18) mW power during typical echo-planar imaging (or fast low angle shot imaging) and usable for stimulating peripheral muscle or nerve to modulate the brain or the gut, with minimal effects on MRI image quality. As a compact and standalone system, the plug-and-play device is suitable for animal research and merits further development for human applications. Introduction:Neurostimulation, e.g. Deep Brain Stimulation (DBS), Vagal Nerve Stimulation (VNS), Spinal Cord Stimulation (SCS), has been widely used to treat Parkinson's disease [1], dystonia [2], [3], epilepsy [4], [5], and intractable pain syndrome [6], [7], to name a few examples. It has also been increasingly recognized that magnetic resonance imaging (MRI) can guide neuromodulation and improve its efficacy, especially if neural stimulation and imaging are performed simultaneously [8]-[12]. However, concurrent stimulation and MRI is non-trivial. A conventional stimulation device may jeopardize patient safety and degrade imaging quality [13], while MRI may interfere with the device and corrupt its function [14]-[16], due to the strong and varying magnetic fields during MRI [17]. In addition, a device often requires long cables to connect to a power source or receive external triggers, where-as such cables may perturb the magnetic fields and degrade image acquisition [18], [19]. Widely used methods for simultaneous MRI and neuromodulation involve non-MR-safe stimulators, which are placed outside the MRI room and connected to the subject using long twisted cables [20]-[23]. The longer stimulation cables sometime pick up fast gradient magnetic fields and lead to unwanted electrical stimulation [24][25]. Few studies include conditionally MRsafe stimulators placed near the MRI bore with shorter cables and RF filtering [26]-[28][29].However, such setups are difficult to scale up, since more stimulation channels would require more cables and RF filtering circuits and amount to an increasingly bulky and complex system.The system also causes patient discomfort, prolongs preparation time, affects imaging quality, especially at a high field (7 Tesla or above) [30].

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Differential effects of vagus nerve stimulation paradigms guide clinical development for Parkinson’s disease

et al. 2020

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Background: Vagus nerve stimulation (VNS) modifies brain rhythms in the locus coeruleus (LC) via the solitary nucleus. Degeneration of the LC in Parkinson's disease (PD) is an early catalyst of the spreading neurodegenerative process, suggesting that stimulating LC output with VNS has the potential to modify disease progression. We previously showed in a lesion PD model that VNS delivered twice daily reduced neuroinflammation and motor deficits, and attenuated tyrosine hydroxylase (TH)-positive cell loss. Objective: The goal of this study was to characterize the differential effects of three clinically-relevant VNS paradigms in a PD lesion model. Methods: Eleven days after DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, noradrenergic lesion, administered systemically)/6-OHDA (6-hydroxydopamine, dopaminergic lesion, administered intrastriatally) rats were implanted with VNS devices, and received either low-frequency VNS, standardfrequency VNS, or high-frequency microburst VNS. After 10 days of treatment and behavioral assessment, rats were euthanized, right prefrontal cortex (PFC) was dissected for norepinephrine assessment, and the left striatum, bilateral substantia nigra (SN), and LC were sectioned for immunohistochemical detection of catecholamine neurons, a-synuclein, astrocytes, and microglia.Results: At higher VNS frequencies, specifically microburst VNS, greater improvements occurred in motor function, attenuation of TH-positive cell loss in SN and LC, and norepinephrine concentration in the PFC.Additionally, higher VNS frequencies resulted in lower intrasomal a-synuclein accumulation and glial density in the SN. Conclusions: These data indicate that higher stimulation frequencies provided the greatest attenuation of behavioral and pathological markers in this PD model, indicating therapeutic potential for these VNS paradigms.

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

Abstract: Background: Vagus nerve stimulation (VNS) is an emerging electroceutical therapy for remedying gastric

Cited by 10 publications

References 47 publications

Differential Effects of Afferent and Efferent Vagus Nerve Stimulation on Gastric Motility Assessed with Magnetic Resonance Imaging

Differential Effects of Afferent and Efferent Vagus Nerve Stimulation on Gastric Motility Assessed with Magnetic Resonance Imaging

MRI Powered and Triggered Current Stimulator for Concurrent Stimulation and MRI

Differential effects of vagus nerve stimulation paradigms guide clinical development for Parkinson’s disease

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