Tragus or cymba conchae? Investigating the anatomical foundation of transcutaneous auricular vagus nerve stimulation (taVNS)

Badran, Bashar W.; Brown, Joshua C.; Dowdle, Logan T.; Mithoefer, Oliver; LaBate, Nicholas T.; Coatsworth, James; DeVries, William H.; Austelle, Christopher W.; McTeague, Lisa M.; Yu, Alfred B.; Bikson, Marom; Jenkins, Dorothea; George, Mark S.

doi:10.1016/j.brs.2018.06.003

Cited by 86 publications

(71 citation statements)

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“…Our stimulation intensity was low, but pre-treating with taVNS or sham first and then running the oddball task with no simultaneous stimulation could address this concern. Finally, there is an unresolved question as to whether the cymba conchae is the best target for taVNS, though both sites yield significant changes in cortical activity [47,61,62]. It is possible that some of our null effects were due to our use of a weak current, a ceiling effect, or a sub-optimal target.…”

Section: Discussionmentioning

confidence: 94%

“…We applied taVNS (NEMOS®, Cerbomed, Germany) with an intensity of 0.5 mA and a pulse width of 200-300 μs at 25 Hz, alternating between on and off periods every 30 s [44][45][46]. In the taVNS condition, the electrodes were applied to the cymba conchae region, which is heavily innervated by the auricular branch of the vagus nerve [47,48] (Fig. 1B).…”

Section: Stimulationmentioning

confidence: 99%

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The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential

et al. 2019

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Background: Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited. Objective: In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings. Methods: Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe. Results: P3 amplitude was not affected by tVNS (Experiment 1A: N=24; Experiment 1B: N=20; Bayes factor supporting null model=4.53), nor was pupil size (Experiment 2: N=16; interaction of treatment and time: p=0.79). However, tVNS increased SAA (Experiments 1A and 2: N=25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N=17), as indicated by significant interactions involving treatment and time (p=.023 and p=.040, respectively). Conclusion: These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function.

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Section: Discussionmentioning

confidence: 94%

Section: Stimulationmentioning

confidence: 99%

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential

et al. 2019

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“…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 and thus there is a need for more such studies to be conducted by individuals with advanced training in microdissection of the head and neck, as the ABVN diameter is only of 1 µm resolution. Teams should also consider age, ethnicity, trauma and prior health history in their selection of cadavers (Badran et al ). fMRI may (in theory) offer a useful surrogate modality for determining the auricular locations that best activate central vagal centres (when compared with the fMRI patterns observed with invasive vagal nerve stimulation), accepting that its use has several limitations.…”

Section: Resultsmentioning

confidence: 99%

The anatomical basis for transcutaneous auricular vagus nerve stimulation

et al. 2019

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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.

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“…We were not able to show an effect of tVNS on the subjective ratings or on the pupillometric results. It is possible that the duration of the applied stimulation was not sufficient, or other stimulation parameters not optimal to induce notable changes in pupil function ( Badran, Mithoefer, et al., 2018 ). Previously, invasive VNS has been shown to induce a pupil dilation, although in that study there were no auditory or other stimuli presented during measurement ( Desbeaumes Jodoin et al., 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Positive Valence in Ratings of Affective Sounds by Tinnitus Patients

Szibor

Ylikoski²,

Aarnisalo

et al. 2018

Trends in Hearing

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Affective processing appears to be altered in tinnitus, and the condition is to a large extent characterized by the emotional reaction to the phantom sound. Psychophysiological models of tinnitus and supporting brain imaging studies have suggested a role for the limbic system in the emergence and maintenance of tinnitus. It is not clear whether the tinnitus-related changes in these systems are specific for tinnitus only, or whether they affect emotional processing more generally. In this study, we aimed to quantify possible deviations in affective processing in tinnitus patients by behavioral and physiological measures. Tinnitus patients rated the valence and arousal of sounds from the International Affective Digitized Sounds database. Sounds were chosen based on the normative valence ratings, that is, negative, neutral, or positive. The individual autonomic response was measured simultaneously with pupillometry. We found that the subjective ratings of the sounds by tinnitus patients differed significantly from the normative ratings. The difference was most pronounced for positive sounds, where sounds were rated lower on both valence and arousal scales. Negative and neutral sounds were rated differently only for arousal. Pupil measurements paralleled the behavioral results, showing a dampened response to positive sounds. Taken together, our findings suggest that affective processing is altered in tinnitus patients. The results are in line with earlier studies in depressed patients, which have provided evidence in favor of the so-called positive attenuation hypothesis of depression. Thus, the current results highlight the close link between tinnitus and depression.

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Tragus or cymba conchae? Investigating the anatomical foundation of transcutaneous auricular vagus nerve stimulation (taVNS)

Cited by 86 publications

References 10 publications

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential

The anatomical basis for transcutaneous auricular vagus nerve stimulation

Attenuation of Positive Valence in Ratings of Affective Sounds by Tinnitus Patients

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