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

Abstract

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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“…[124][125][126][127] Furthermore, ES of the spinal cord is used to restore or improve the movements and sensation defaults, or even for tracts regeneration in the white matter through the spinal cord. [23,24,[128][129][130] In addition, ES electroceutical therapy has been utilized on autonomic nerves that consist of the cervical gastric vagus nerve [131][132][133][134] and sacral nerves. [135,136] Furthermore, some other neurological diseases such as multiple sclerosis and Alzheimer's disease interrupt the transmission of the neural signal.…”

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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]. The time series represented the cross-sectional area change of a particular plane.…”