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Biomedical Engineering / Biomedizinische Technik

Editor-in-Chief: Dössel, Olaf

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Volume 53, Issue 3 (Jun 2008)

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Volume 57 (2012)

A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI / Funktionelle Magnetresonanztomographie zeigt Aktivierungen des Hirnstamms und weiterer zerebraler Strukturen unter transkutaner Vagusnervstimulation

Stefan Dietrich / James Smith
  • 2Centre for Medical Physics and Technology, Biophysics Group, University Erlangen-Nuremberg, Erlangen, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Charlotte Scherzinger / Karina Hofmann-Preiß / Timo Freitag / Alexander Eisenkolb / Ralf Ringler
Published Online: 2008-06-11 | DOI: https://doi.org/10.1515/BMT.2008.022

Abstract

Background: Left cervical vagus nerve stimulation (VNS) using the implanted NeuroCybernetic Prosthesis (NCP®) can reduce epileptic seizures and has recently been shown to give promising results for treating therapy-resistant depression. To address a disadvantage of this state-of-the-art VNS device, the use of an alternative transcutaneous electrical nerve stimulation technique, designed for muscular stimulation, was studied. Functional magnetic resonance imaging (MRI) has been used to test non-invasively access nerve structures associated with the vagus nerve system. The results and their impact are unsatisfying due to missing brainstem activations. These activations, however, are mandatory for reasoning, higher subcortical and cortical activations of vagus nerve structures. The objective of this study was to test a new parameter setting and a novel device for performing specific (well-controlled) transcutaneous VNS (tVNS) at the inner side of the tragus. This paper shows the feasibility of these and their potential for brainstem and cerebral activations as measured by blood oxygenation level dependent functional MRI (BOLD fMRI).

Materials and methods: In total, four healthy male adults were scanned inside a 1.5-Tesla MR scanner while undergoing tVNS at the left tragus. We ensured that our newly developed tVNS stimulator was adapted to be an MR-safe stimulation device. In the experiment, cortical and brainstem representations during tVNS were compared to a baseline.

Results: A positive BOLD response was detected during stimulation in brain areas associated with higher order relay nuclei of vagal afferent pathways, respectively the left locus coeruleus, the thalamus (left≫right), the left prefrontal cortex, the right and the left postcentral gyrus, the left posterior cingulated gyrus and the left insula. Deactivations were found in the right nucleus accumbens and the right cerebellar hemisphere.

Conclusion: The method and device are feasible and appropriate for accessing cerebral vagus nerve structures, respectively. As functional patterns share features with fMRI BOLD, the effects previously studied with the NCP® are discussed and new possibilities of tVNS are hypothesised.

Zusammenfassung

Hintergrund: Die Vagusnervstimulation am linken Halsstrang mit einer implantierten neurokybernetischen Prothese hat sich als suffizient bei der Behandlung von epileptischen Episoden erwiesen und zeigt zudem vielversprechende Behandlungsansätze für therapieresistente Depressionen. Aufgrund zahlreicher Nachteile einer derzeit alleinig verfügbaren implantologischen Lösung wurden in der letzten Zeit Studien zur Verwendung der transkutanen elektrischen Nervenstimulation, die hauptsächlich der Muskelstimulation dient, als nicht-invasiver Zugang zu Hirnstamm- und Kortexstrukturen über afferente Vagusnervfasern am menschlichen Ohr unter Verwendung der funktionellen Magnetresonanztomographie durchgeführt. Die Resultate und Folgerungen dieser Studien sind aber fragwürdig, da keine Aktivierungen des Hirnstamms ermittelt wurden. Diese allerdings sind für eine Aktivierung höherer Zentren unbedingt notwendig. Aufgabe der hier vorliegenden Arbeit war es daher, eine Methode und ein Gerät zur transkutanen Vagusnervstimulation (tVNS) an der Innenseite des Tragus zu entwickeln, welche auch eine solche Hirnstammaktiverung ermöglichen, und diese unter Zuhilfenahme des BOLD-Effekts (blood oxygenation level dependent functional magnetic resonance imaging, BOLD fMRI) basierend auf der funktionellen Magnetresonanztomographie zu studieren.

Material und Methode: Vier männliche und gesunde Probanden wurden während tVNS an der linken Ohrmuschel in einem 1,5-Tesla-MR-Scanner untersucht. Hierfür wurde eine speziell konstruierte MR-taugliche Stimulationseinheit entwickelt und verwendet. In diesem Experiment wurden die BOLD-Effekte in Phasen während der Stimulation mit Ruhephasen ohne Stimulation verglichen.

Ergebnisse: Positive BOLD-Effekte während der Stimulation traten insbesondere in Hirnarealen auf, welche Relais höherer Ordnung für vagale Afferenzen darstellen, wie dem Locus coeruleus, dem Thalamus (links≫rechts), dem linken präfrontalen Kortex, dem rechten und linken Gyrus postcentralis, dem linken hinteren Gyrus cinguli und der linken Inselregion. Deaktivierungen wurden im rechten Nucleus accumbens und der rechten Kleinhirnhemisphäre sichtbar.

Schlussfolgerung: Vorgeschlagene Methode und Gerät können zerebrale Strukturen des Vagusnervsystems, insbesondere auch Hirnstammareale, aktivieren. Die Aktivierungsmuster unter tVNS ähneln jenen der zerebralen regionalen Blutflussänderungen aus früheren Studien unter Verwendung der NCP. Daher scheinen neue diagnostische und therapeutische Ansätze zumindest theoretisch möglich zu sein.

Keywords: blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI); pinna; transcutaneous vagus nerve stimulation (tVNS); vagus nerve stimulation; blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI); Ohrmuschel; transkutane Vagusnervstimulation (tVNS); Vagusnervstimulation

About the article

Corresponding author: Stefan Dietrich, cerboMed GmbH, Henkestr. 91, 91052 Erlangen, Germany Phone: +49-9131-9202760 Fax: +49-9131-92027692


Received: 2007-07-03

Accepted: 2008-03-28

Published Online: 2008-06-11

Published in Print: 2008-06-01


Citation Information: Biomedizinische Technik/Biomedical Engineering, ISSN (Online) 1862-278X, ISSN (Print) 0013-5585, DOI: https://doi.org/10.1515/BMT.2008.022.

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