Evidence for a modulating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on salivary alpha-amylase as indirect noradrenergic marker: A pooled mega-analysis

Manon Giraudier; Carlos Ventura-Bort; Andreas M Burger; Nathalie Claes; Martina D'Agostini; Rico Fischer; Mathijs Franssen; Michael Kaess; Julian Koenig; Roman Liepelt; Sander Nieuwenhuis; Aldo Sommer; Taras Usichenko; Ilse Van Diest; Andreas von Leupoldt; Christopher M Warren; Mathias Weymar

doi:10.1016/j.brs.2022.09.009

Evidence for a modulating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on salivary alpha-amylase as indirect noradrenergic marker: A pooled mega-analysis

Brain Stimul. 2022 Nov-Dec;15(6):1378-1388. doi: 10.1016/j.brs.2022.09.009. Epub 2022 Sep 30.

Authors

Manon Giraudier¹, Carlos Ventura-Bort², Andreas M Burger³, Nathalie Claes³, Martina D'Agostini³, Rico Fischer⁴, Mathijs Franssen³, Michael Kaess⁵, Julian Koenig⁶, Roman Liepelt⁷, Sander Nieuwenhuis⁸, Aldo Sommer⁹, Taras Usichenko¹⁰, Ilse Van Diest³, Andreas von Leupoldt³, Christopher M Warren¹¹, Mathias Weymar¹²

Affiliations

¹ Department of Biological Psychology and Affective Science, Faculty of Human Sciences, University of Potsdam, Potsdam, Germany. Electronic address: manon.giraudier@uni-potsdam.de.
² Department of Biological Psychology and Affective Science, Faculty of Human Sciences, University of Potsdam, Potsdam, Germany.
³ Research Group Health Psychology, KU Leuven, Leuven, Belgium.
⁴ Department of Psychology, University of Greifswald, Greifswald, Germany.
⁵ University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland; Department of Child and Adolescent Psychiatry, Centre for Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.
⁶ University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Cologne, Germany.
⁷ Department of General Psychology: Judgment, Decision Making, Action, Faculty of Psychology, University of Hagen (FernUniversität in Hagen), Hagen, Germany.
⁸ Institute of Psychology, Leiden University, Netherlands; Leiden Institute for Brain and Cognition, Leiden University, Netherlands.
⁹ Department of General Psychology: Judgment, Decision Making, Action, Faculty of Psychology, University of Hagen (FernUniversität in Hagen), Hagen, Germany; Department of Exercise Physiology, German Sport University Cologne, Cologne, Germany.
¹⁰ Department of Anesthesiology, University Medicine of Greifswald, Greifswald, Germany; Department of Anesthesia, McMaster University, Hamilton, Canada.
¹¹ Emma Eccles Jones College of Education and Human Services, Utah State University, United States.
¹² Department of Biological Psychology and Affective Science, Faculty of Human Sciences, University of Potsdam, Potsdam, Germany; Faculty of Health Sciences Brandenburg, University of Potsdam, Potsdam, Germany. Electronic address: mathias.weymar@uni-potsdam.de.

PMID: 36183953
DOI: 10.1016/j.brs.2022.09.009

Abstract

Background: Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has received tremendous attention as a potential neuromodulator of cognitive and affective functions, which likely exerts its effects via activation of the locus coeruleus-noradrenaline (LC-NA) system. Reliable effects of taVNS on markers of LC-NA system activity, however, have not been demonstrated yet.

Methods: The aim of the present study was to overcome previous limitations by pooling raw data from a large sample of ten taVNS studies (371 healthy participants) that collected salivary alpha-amylase (sAA) as a potential marker of central NA release.

Results: While a meta-analytic approach using summary statistics did not yield any significant effects, linear mixed model analyses showed that afferent stimulation of the vagus nerve via taVNS increased sAA levels compared to sham stimulation (b = 0.16, SE = 0.05, p = 0.001). When considering potential confounders of sAA, we further replicated previous findings on the diurnal trajectory of sAA activity.

Conclusion(s): Vagal activation via taVNS increases sAA release compared to sham stimulation, which likely substantiates the assumption that taVNS triggers NA release. Moreover, our results highlight the benefits of data pooling and data sharing in order to allow stronger conclusions in research.

Keywords: Biomarker; Data pooling; Non-invasive vagus nerve stimulation; Noradrenaline; sAA; tVNS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Salivary alpha-Amylases*
Transcutaneous Electric Nerve Stimulation* / methods
Vagus Nerve / physiology
Vagus Nerve Stimulation* / methods

Substances

Salivary alpha-Amylases