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.

Keywords: Acupuncture therapy; Autonomic nervous system; Cadaver; Cardiovascular system; Cranial nerves; Electrical stimulation; Magnetic resonance imaging; Neuroanatomy; Pain; Vagus nerve; Vagus nerve stimulation.

Conflict of interest statement

There are no known conflicts of interest associated with the publication of this work. No author received financial support.

© 2019 Anatomical Society.

Figures

Figure 1

Diagram of the external ear and its hypothesised cutaneous innervation. Permissions: No permissions required

Figure 2

A schematic diagram of the approximate relationships between the facial, glossopharyngeal and vagus nerves. The ABVN originates from the petrous ganglion of the glossopharyngeal nerve and jugular ganglion of the vagus nerve and ascends through the mastoid canaliculus. In the mastoid, it crosses the fallopian canal 3–4 mm above the stylomastoid foramen and divides into two branches. The first branch of the ABVN has a connection with the chorda tympani and supplies the sensory part of the posterior cranial fossa dura mater, while the second branch supplies the posterior skin of the external auditory meatus and adjacent tympanic membrane. The second branch has an inferior division connecting to the posterior auricular branch of the facial nerve after exiting the stylomastoid foramen. ABVN, auricular branch of the vagus nerve; CT, chorda tympani nerve; FN, facial nerve; TBGN, tympanic branch of the glossopharyngeal nerve. Permissions: No permissions required.

Figure 3

A schematic diagram of external auricle afferent projections to the brainstem and upper cervical spinal cord. (A) In the brainstem, the greater auricular nerve (green) projects into the trigeminal tract, cuneate nucleus and a little in the nucleus of the solitary tract. The auriculotemporal nerve (red) terminates in the trigeminal tract, caudal trigeminal nucleus and cuneate nucleus. The ABVN (blue) is projected into the nucleus of the solitary tract, cuneate nucleus, and caudal trigeminal nucleus. (B) Projection of the greater auricular nerve into upper cervical cord has wide coverage from laminae I to laminae V, and smaller coverage by the auriculotemporal nerve concentrated in the laminae III–IV. The ABVN afferents terminate in the laminae I‐IV. The level central nervous axis was omitted for clarity. Permissions: We wish to thank Prof. Jim Deuchars (University of Leeds) and Dr Mohd Kaisan Bin Mahadi for providing this figure. No formal permissions required.

Figure 4

Auricular acupoints. Permissions: No permissions required.

Figure 5

Two possible mechanisms for parasympathetic activation via the auricular branch of the vagus nerve (ABVN). The blue arrows represent the activation of vagal afferents and stimulation of the main vagal bundle via the central nervous system. The red arrow represents the direct activation of vagal efferents and stimulation of the main vagal bundle. Permissions: No permissions required.

Figure 6

A schematic diagram of one of the hypothesised pathways through which stimulation of the auricular branch of the vagus nerve (ABVN) can influence the cardiovascular system Stimulation of the ABVN increases input to the nucleus of the solitary tract (NTS) in the medulla and influences the activity of NTS neurones projecting to the cardioinhibitory vagal efferent neurones of the dorsal vagal nucleus (DVN) and nucleus ambiguous (NA). These vagal efferent neurones propagate the vagal tone to the sinoatrial node (SA). Stimulation of the ABVN may also excite NTS neurons, sending excitatory projections to the caudal ventrolateral medulla (CVLM). The CVLM inhibits the rostroventrolateral medulla (RVLM), which is the primary source of excitatory drive to sympathetic preganglionic neurons in the intermediolateral cell column (IML) of the spinal cord. This inhibition would decrease sympathetic activity. Permissions: No permissions required.