Heart Rate Variability as a Biomarker for Electrical Vagus Nerve Stimulation

Electrical vagus nerve stimulation (eVNS) comprises an array of non-pharmacologic techniques used to stimulate afferent fibers of the vagus nerve. Despite the increasing use of eVNS both in clinical settings and in research, there is still a need for a valid biological marker that can be used to indicate the action of eVNS in the central as well as in the peripheral nervous system. The present chapter focuses on one of the most prominent candidates for such a biomarker, namely, heart rate variability (HRV). We provide arguments for the s of specific HRV parameters to this aim, namely, vagally-mediated HRV, which reflects cardiac vagal activity. We describe the mechanism of action underlying the expected effects of eVNS on cardiac vagal activity and perform a literature review, which shows mixed evidence on the increase of cardiac vagal activity due to eVNS. Furthermore, we point out relevant methodological caveats of current literature on eVNS and discuss how to avoid them in a study designed to investigate the relationship between eVNS and cardiac vagal activity. Based on this, we describe what is necessary to properly measure cardiac vagal activity during the use of eVNS, and discuss considerations that need to be observed when it comes to designing studies that aim to address this relationship.