Selective Stimulation of Vagal Pathways Using a Multi‐contact Circumferential Cuff Electrode

Abstract

Vagus nerve stimulation (VNS) has been used to treat epileptic seizures, depression, cardiovascular disease, and obesity; however, non‐selective vagal stimulation can produce adverse side effects, such as nausea and reduced blood pressure. The current study was designed to assess the potential for a precision, multi‐contact nerve cuff electrode to produce selective and discrete activation of vagus nerve fibers. We used an acute anesthetized ferret preparation (n = 6) to test the effects of an abdominal vagus nerve electrode (Micro‐Leads Neuro) on cellular responses (compound action potential, CAP) recorded from a 32‐channel microelectrode array (MEA) inserted into the nodose ganglion. We investigated the selectivity of nodose responses by varying: (1) electrode contact stimulation pair; (2) pulse width, using 0.1, 0.5, and 1.0 ms; and (3) pulse amplitude, steps of 20 μA. Stimulation was delivered at 2 Hz using the average response from 120 pulses per trial. Selectivity was quantified by the number of MEA channels responding to only one of the two cuff stimulation pairs. Across all animals, stimulation selectively evoked responses recorded by multiple different contacts in the MEA. In a similar experimental setup in three additional animals, multi‐contact stimulation of the abdominal vagus was used to drive changes in gastric myoelectric activity (GMA), as assessed by a set of four to six 4‐contact electrode planar arrays (Micro‐Leads Neuro) sutured to the serosal surface of the stomach. In one animal, selective stimulation drove changes in GMA without a concomitant change in heart rate (HR) or respiration rate (RR), while in two other animals, there was a selective change in HR or RR without a change in GMA. The present study supports the viability of producing selective responses from multi‐contact abdominal vagus nerve cuff electrodes and suggests the need to further investigate the effects of selective VNS on end‐organ therapeutic and off‐target effects, such as gastrointestinal motility, heart rate, blood pressure, inflammatory responses, and metabolic effects (e.g., blood cytokine levels and insulin release).Support or Funding InformationThis research was supported by funding from the NIH SPARC Common Fund Program (award #U18TR002205).