title: CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study.
abstract: BACKGROUND
  It has recently been shown that electrical stimulation of sensory afferents within the outer auditory canal may facilitate a transcutaneous form of central nervous system stimulation. Functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) effects in limbic and temporal structures have been detected in two independent studies. In the present study, we investigated BOLD fMRI effects in response to transcutaneous electrical stimulation of two different zones in the left outer auditory canal. It is hypothesized that different central nervous system (CNS) activation patterns might help to localize and specifically stimulate auricular cutaneous vagal afferents.
  
  
  METHODS
  16 healthy subjects aged between 20 and 37 years were divided into two groups. 8 subjects were stimulated in the anterior wall, the other 8 persons received transcutaneous vagus nervous stimulation (tVNS) at the posterior side of their left outer auditory canal. For sham control, both groups were also stimulated in an alternating manner on their corresponding ear lobe, which is generally known to be free of cutaneous vagal innervation. Functional MR data from the cortex and brain stem level were collected and a group analysis was performed.
  
  
  RESULTS
  In most cortical areas, BOLD changes were in the opposite direction when comparing anterior vs. posterior stimulation of the left auditory canal. The only exception was in the insular cortex, where both stimulation types evoked positive BOLD changes. Prominent decreases of the BOLD signals were detected in the parahippocampal gyrus, posterior cingulate cortex and right thalamus (pulvinar) following anterior stimulation. In subcortical areas at brain stem level, a stronger BOLD decrease as compared with sham stimulation was found in the locus coeruleus and the solitary tract only during stimulation of the anterior part of the auditory canal.
  
  
  CONCLUSIONS
  The results of the study are in line with previous fMRI studies showing robust BOLD signal decreases in limbic structures and the brain stem during electrical stimulation of the left anterior auditory canal. BOLD signal decreases in the area of the nuclei of the vagus nerve may indicate an effective stimulation of vagal afferences. In contrast, stimulation at the posterior wall seems to lead to unspecific changes of the BOLD signal within the solitary tract, which is a key relay station of vagal neurotransmission. The results of the study show promise for a specific novel method of cranial nerve stimulation and provide a basis for further developments and applications of non-invasive transcutaneous vagus stimulation in psychiatric patients.
authors: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany; Frankenalb-Klinik Engelthal, Clinic for Psychiatry, Psychotherapy, Psychosomatic Medicine, and Addiction Rehabilitation, Germany. Electronic address: mail@thomaskraus.de.
authors: Thomas
authors: T
authors: Kraus
authors: Olga
authors: O
authors: Kiess
authors: Katharina
authors: K
authors: Hösl
authors: Pavel
authors: P
authors: Terekhin
authors: Johannes
authors: J
authors: Kornhuber
authors: Clemens
authors: C
authors: Forster
mesh_terms: D000328:Adult; D000344:Afferent Pathways / Q000502:physiology; D001921:Brain / Q000502:physiology*; D004424:Ear Canal / Q000294:innervation*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010865:Pilot Projects; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*; D055536:Vagus Nerve Stimulation / Q000379:methods*; D055815:Young Adult
keywords: Anti-depressant; BOLD; Brain stimulation; Non-invasive; Psychiatric; TENS; Transcutaneous vagus nerve stimulation; VNS; Vagus nerve stimulation; fMRI; t-VNS; tVNS