Anodal block permits directional vagus nerve stimulation

Umair Ahmed,Stavros Zanos,Yousef Al-Abed,Yao-Chuan Chang,Jacquelyn N Tomaio,Maria F Lopez,Timir Datta-Chaudhuri,Theodoros P Zanos,Marina Cracchiolo,Loren Rieth

doi:10.1038/s41598-020-66332-y

Umair Ahmed, Stavros Zanos + Show 8 more

Open Access

https://doi.org/10.1038/s41598-020-66332-y

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Abstract

Vagus nerve stimulation (VNS) is a bioelectronic therapy for disorders of the brain and peripheral organs, and a tool to study the physiology of autonomic circuits. Selective activation of afferent or efferent vagal fibers can maximize efficacy and minimize off-target effects of VNS. Anodal block (ABL) has been used to achieve directional fiber activation in nerve stimulation. However, evidence for directional VNS with ABL has been scarce and inconsistent, and it is unknown whether ABL permits directional fiber activation with respect to functional effects of VNS. Through a series of vagotomies, we established physiological markers for afferent and efferent fiber activation by VNS: stimulus-elicited change in breathing rate (ΔBR) and heart rate (ΔHR), respectively. Bipolar VNS trains of both polarities elicited mixed ΔHR and ΔBR responses. Cathode cephalad polarity caused an afferent pattern of responses (relatively stronger ΔBR) whereas cathode caudad caused an efferent pattern (stronger ΔHR). Additionally, left VNS elicited a greater afferent and right VNS a greater efferent response. By analyzing stimulus-evoked compound nerve potentials, we confirmed that such polarity differences in functional responses to VNS can be explained by ABL of A- and B-fiber activation. We conclude that ABL is a mechanism that can be leveraged for directional VNS.

Highlights

Vagus nerve stimulation (VNS) is a bioelectronic therapy for disorders of the brain and peripheral organs, and a tool to study the physiology of autonomic circuits
In order to determine physiological indicators of afferent and efferent vagal fiber activation in response to cervical VNS, experiments were performed in which both polarity configurations of VNS were first delivered with the vagus intact, and, using the same stimulation parameters, after rostral or caudal vagotomy; the configuration with the greater response before the vagotomy was included in the analysis
In animals with an intact vagus, cervical VNS at supra-threshold intensity produced a drop in both heart rate (HR) and breathing rate (BR) (Fig. 1a); after rostral vagotomy, the drop in breathing rate disappeared but there was still a comparable drop in HR (Fig. 1b)

Summary

Introduction

Vagus nerve stimulation (VNS) is a bioelectronic therapy for disorders of the brain and peripheral organs, and a tool to study the physiology of autonomic circuits. It has been shown that VNS polarity has an effect on stimulus-evoked fiber activation[23], but there were no corresponding functional or physiologic outcomes reported; [28] an effect of polarity on an efferent index of activation has been reported, but without documentation of afferent effects or of evoked activation of nerve fibers It is unclear whether anodal block in VNS is a viable mechanism to directionally control fiber activation in VNS and, if so, what degree of directional selectivity it can provide. We conducted a series of vagotomy experiments to establish physiological markers of afferent and efferent vagal fiber activation in response to cervical VNS: stimulus-elicited changes in breathing rate and heart rate, respectively. Our study provides concrete physiological and neurophysiological evidence that anodal block is a viable mechanism for functionally demonstrable directional biasing in VNS, for a range of clinically relevant stimulation parameters

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