The anatomical basis for transcutaneous auricular vagus nerve stimulation

Abstract

The array of end organ innervations of the vagus nerve, coupled with increased basic science evidence, has led to vagus nerve stimulation (VNS) being explored as a management option in a number of clinical disorders, such as heart failure, migraine and inflammatory bowel disease. Both invasive (surgically implanted) and non‐invasive (transcutaneous) techniques of VNS exist. Transcutaneous VNS (tVNS) delivery systems rely on the cutaneous distribution of vagal afferents, either at the external ear (auricular branch of the vagus nerve) or at the neck (cervical branch of the vagus nerve), thus obviating the need for surgical implantation of a VNS delivery device and facilitating further investigations across a wide range of uses. The concept of electrically stimulating the auricular branch of the vagus nerve (ABVN), which provides somatosensory innervation to several aspects of the external ear, is relatively more recent compared with cervical VNS; thus, there is a relative paucity of literature surrounding its operation and functionality. Despite the increasing body of research exploring the therapeutic uses of auricular transcutaneous VNS (tVNS), a comprehensive review of the cutaneous, intracranial and central distribution of ABVN fibres has not been conducted to date. A review of the literature exploring the neuroanatomical basis of this neuromodulatory therapy is therefore timely. Our review article explores the neuroanatomy of the ABVN with reference to (1) clinical surveys examining Arnold’s reflex, (2) cadaveric studies, (3) fMRI studies, (4) electrophysiological studies, (5) acupuncture studies, (6) retrograde tracing studies and (7) studies measuring changes in autonomic (cardiovascular) parameters in response to auricular tVNS. We also provide an overview of the fibre composition of the ABVN and the effects of auricular tVNS on the central nervous system. Cadaveric studies, of which a limited number exist in the literature, would be the ‘gold‐standard’ approach to studying the cutaneous map of the ABVN; thus, there is a need for more such studies to be conducted. Functional magnetic resonance imaging (fMRI) represents a useful surrogate modality for discerning the auricular sites most likely innervated by the ABVN and the most promising locations for auricular tVNS. However, given the heterogeneity in the results of such investigations and the various limitations of using fMRI, the current literature lacks a clear consensus on the auricular sites that are most densely innervated by the ABVN and whether the brain regions secondarily activated by electrical auricular tVNS depend on specific parameters. At present, it is reasonable to surmise that the concha and inner tragus are suitable locations for vagal modulation. Given the therapeutic potential of auricular tVNS, there remains a need for the cutaneous map of the ABVN to be further refined and the effects of various stimulation parameters and stimulation sites to be determined.

The Impact of Auricular Vagus Nerve Stimulation on Pain and Life Quality in Patients with Fibromyalgia Syndrome

“…The current knowledge lacks a clear consensus on the sites that are most suitable for stimulation of the auricular branch of the vagus nerve. When the studies up to today are evaluated, it can be said that the concha and inner tragus appear to be good locations for vagal neuromodulation [23]. We used a new design ear set to stimulate both parts of the auricular vagus bilaterally.…”

Reduced Frontal Nogo-N2 With Uncompromised Response Inhibition During Transcutaneous Vagus Nerve Stimulation—More Efficient Cognitive Control?

“…Moreover, cymba conchae have been suggested to be a more efficient location to stimulate vagus nerve compared to the inner surface of the tragus used in the current study (Ellrich, 2019 ). On the other hand, fMRI studies have shown similar brain effects when stimulating either location (Kraus et al, 2007 ; Dietrich et al, 2008 ; Badran et al, 2018a ) and according to review by Butt et al ( 2019 ), based on the anatomy of the vagus nerve innervations there is no clear difference between the two locations. However, to assess the potential for enhancing cognitive functions with tVNS, future studies are needed to assess whether the impact of tVNS on brain functions depends on baseline cognitive performance, on the stimulation location, or other stimulation parameters.…”

“…Executive functions rely heavily on noradrenergic transmission and increased noradrenaline (NA) levels have been shown to improve executive functions in rodents (Roosevelt et al, 2006 ; Grimonprez et al, 2015b ), and to improve performance in human clinical populations with deficits in executive functions (Neuhaus et al, 2007 ; De Taeye et al, 2014 ). The neural effects of tVNS and VNS are thought to be based on the anatomical connections of the vagus nerve (VN) to brain stem nuclei releasing neurotransmitters such as NA in many brain regions via widespread connections (Fanselow, 2012 ; Butt et al, 2019 ). tVNS excites the afferent fibers of the auricular branch of the VN in the ear while VNS excites the cervical trunk of the VN.…”

Transcutaneous Vagus Nerve Stimulation May Enhance Only Specific Aspects of the Core Executive Functions. A Randomized Crossover Trial

“…However, it lacks substantial evidence that electrical stimulation on the earlobe cannot stimulate brain center nuclei that trigger an increase in cardiac vagal outflow (Rangon, 2018). This is especially relevant because the boundaries between particular dermatomes often overlap (Butt et al, 2019), so that a clear understanding of the nerve distribution of the human auricle is needed. Regardless of the suitability of the earlobe, it has also been discussed whether vmHRV parameters are sensitive to afferent vagal changes triggered by tVNS; it is not yet clear whether the electrical signal produced by tVNS is strong enough to overcome bodyrelated barriers such as skin and blood vessels, and therefore to trigger vagal afferent firing in a way that would robustly increase prefrontal activity, thus indirectly affecting cardiac vagal activity (Borges et al, 2019).…”