Vagus Nerve Stimulation in the Non-Human Primate: Implantation Methodology, Characterization of Nerve Anatomy, Target Engagement and Behavioral Utility

Background: Vagus nerve stimulation (VNS) is regularly used to treat a variety of neurological disorders that impact the central nervous system (CNS). There are, however, few large animal models that allow for detailed mechanistic studies of the effects of VNS on the CNS during behavior. Methods: To that end, we describe the anatomical organization, surgical methodology to implant VNS electrodes and characterization of target engagement/neural interface properties in a non-human primate (NHP) model of VNS that permits chronic stimulation over long periods of time. Furthermore, we demonstrate the utility of this preparation in low n, proof of concept behavioral and imaging experiments investigating the effects of VNS on the CNS. Results: VNS electrode impedance remained constant over months suggesting a stable interface. VNS elicited robust activation of the vagus nerve which resulted in decreases of respiration rate and/or partial pressure of carbon dioxide in expired air, but not changes in heart rate in both awake and anesthetized NHPs. Conclusions: We anticipate that this preparation will be very useful to study the mechanisms underlying the effects of VNS for the treatment of conditions such as epilepsy and depression, for which VNS is extensively used, as well as for the study of the neurobiological basis underlying higher order functions such as learning and memory.