Highlights
- •Electrical stimulation of the cymba conchae activates the NTS in humans.
- •Activations and deactivations of vagal projections were found throughout the brain.
- •The pattern of activity can account for the beneficial effects of t-VNS and VNS.
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 NTS, 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.
Keywords
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Article info
Publication history
Published online: December 05, 2014
Accepted:
November 29,
2014
Received in revised form:
November 28,
2014
Received:
September 14,
2014
Footnotes
Financial Disclosures: This study was supported by Cerbomed, GmbH (Erlangen, Germany) and by the National Institutes of Health Grant 2R25 GM 060826.
Conflict of interest: Funding for this research (e.g., fMRI scan costs and honoraria to research participants) was provided by a grant from Cerbomed, GmbH, Erlangen, Germany. Cerbomed, the manufacturer of the ear stimulator, provided the instruments for this study. JE was the Chief Medical Officer of Cerbomed during the early part of this study; he is no longer affiliated with the company. BRK is a paid consultant and member of the Advisory Board of Cerbomed. EF received financial compensation from Cerbomed to support the fMRI data analysis. No contractual relations or proprietary considerations exist that restrict the dissemination of our findings.
Preliminary findings have been published abstract form [16–18].
Identification
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© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
