Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans

Abstract

Background Tract-tracing studies in cats and rats demonstrated that the auricular branch of the vagus nerve (ABVN) projects to the nucleus tractus solitarii (NTS); it has remained unclear as to whether or not the ABVN projects to the NTS in humans. Objective To ascertain whether non-invasive electrical stimulation of the cymba conchae, a region of the external ear exclusively innervated by the ABVN, activates the NTS and the “classical” central vagal projections in humans. Methods Twelve healthy adults underwent two fMRI scans in the same session. Electrical stimulation (continuous 0.25ms pulses, 25Hz) was applied to the earlobe (control, scan #1) and left cymba conchae (scan #2). Statistical analyses were performed with FSL. Two region-of-interest analyses were performed to test the effects of cymba conchae stimulation (compared to baseline and control, earlobe, stimulation) on the central vagal projections (corrected; brainstem p<0.01, forebrain p<0.05), followed by a whole-brain analysis (corrected, p< 0.05). Results Cymba conchae stimulation, compared to earlobe (control) stimulation, produced significant activation of the “classical” central vagal projections, e.g., widespread activity in the ipsilateral nucleus of the solitary tract, bilateral spinal trigeminal nucleus, dorsal raphe, locus coeruleus, and contralateral parabrachial area, amygdala, and nucleus accumbens. Bilateral activation of the paracentral lobule was also observed. Deactivations were observed bilaterally in the hippocampus and hypothalamus. Conclusion These findings provide evidence in humans that the central projections of the ABVN are consistent with the “classical” central vagal projections and can be accessed non-invasively via the external ear.

Transcutaneous vagus nerve stimulation (tVNS) modulates flow experience

“…In an influential study, Fallgatter et al (2003) stimulated the tragus and showed that active tVNS, compared to sham, produced a clear and reliable vagus sensory evoked potential in healthy participants. Further, two functional magnetic resonance imaging (MRI) studies in healthy humans have found that tVNS increased activation in the brainstem region including the locus coeruleus (LC) and nucleus of the solitary tract, indicating that tVNS is able to effectively stimulate vagal afferents to the brainstem (Dietrich et al 2008;Frangos et al 2015). In rats, it has been shown that VNS leads to an intensity-dependent increase in brain norepinephrine (NE) in response to stimulation of the left vagus nerve (Raedt et al 2011;Roosevelt et al 2006).…”

Effects of chronic abdominal vagal stimulation of small-diameter neurons on brain metabolism and food intake

“…A recent study was able to observe a widespread activation of the NTS by cymbal conchae stimulation in human. However, the parameters used for brainstem analysis were insufficiently conservative (33). In contrast, we used highly conservative parameters (18) and consequently the number and size of the activated areas are robust.…”

Is-there a place for vagus nerve stimulation in inflammatory bowel diseases?

“…Lesions of the LC block the anti-epileptic and anti-depressant effects of VNS (Krahl et al, 1998). VNS increases firing rates of LC neurons and norepinephrine concentrations in the cortex and hippocampus, two projection sites of the LC (Dorr & Debonnel, 2006;Roosevelt et al, 2006) and activates the LC in a fMRI study in humans (Frangos et al, 2015). VNS may act initially and/or predominantly on the LC, and indirectly with the dorsal raphe nucleus via afferents from the LC (Dorr & Debonnel, 2006).…”

“…Devices stimulating the VN at the cervical level or at the auricular level have been developed. Indeed, the cymba concha of the external ear is innervated by a sensory auricular branch of the VN (Peuker & Filler, 2002) that sends projection in the NTS in cats (Nomura & Mizuno, 1984) and humans (Frangos et al, 2015). Transauricular (ta) VNS could thus activate the CAP through an inflammatory reflex.…”