title: 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychology, Rutgers University, 101 Warren St, Newark, NJ 07102, USA. Electronic address: frangos.eleni@gmail.com.
authors.forename: Eleni
authors.initials: E
authors.lastname: Frangos
authors.affiliation: Cerbomed GmbH, Henkestrasse 91, 91052 Erlangen, Germany; Department of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 7D2, DK-9220 Aalborg, Denmark; Institute of Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuremberg, Universitaetsstrasse 17, D-91054 Erlangen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Ellrich
authors.affiliation: Department of Psychology, Rutgers University, 101 Warren St, Newark, NJ 07102, USA.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Komisaruk
mesh_terms: D000328:Adult; D000368:Aged; D000679:Amygdala / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D004431:Ear, External / Q000294:innervation* / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D008125:Locus Coeruleus / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017552:Solitary Nucleus / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*; D055536:Vagus Nerve Stimulation; D055815:Young Adult
keywords: Neuromodulation; Non-invasive vagus stimulation; Nucleus of the solitary tract; Vagus nerve auricular branch; fMRI; t-VNS