Prefrontal cortex oxygenation and autonomic nervous system activity under transcutaneous auricular vagus nerve stimulation in adolescents

  • Saskia Höper
    Department of Child and Adolescent Psychiatry, Centre for Psychosocial Medicine, Heidelberg University, Heidelberg, Germany
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  • Michael Kaess
    Department of Child and Adolescent Psychiatry, Centre for Psychosocial Medicine, Heidelberg University, Heidelberg, Germany

    University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
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  • Julian Koenig
    Corresponding author at: Clinic and Polyclinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Cologne, Robert-Koch-Straße 10 (Building 53), 50931 Cologne, Germany.
    Department of Child and Adolescent Psychiatry, Centre for Psychosocial Medicine, Heidelberg University, Heidelberg, Germany

    University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland

    University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Cologne, Germany
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      • Heart rate (HR) decreased under transcutaneous vagus nerve stimulation (tVNS).
      • Heart rate variability (HRV) increased under tVNS.
      • Prefrontal cortex (PFC) oxygenation increased under tVNS.
      • Greater PFC oxygenation was associated with greater HRV and lower HR under tVNS.
      • Exploratory analyses illustrated increased PFC connectivity under tVNS.



      The Neurovisceral Integration Model (NIM) proposes a complex interplay of visceral and neural structures that are crucial for adaptive responses to environmental demands. The aim of the present study was to investigate this circuitry using experimental manipulation via transcutaneous auricular vagus nerve stimulation (tVNS), measures of peripheral autonomic nervous system (ANS) activity and prefrontal cortex (PFC) oxygenation, quantified using functional near-infrared spectroscopy (fNIRS).


      In a sample of n = 30 adolescents (age 14–17 years), tVNS versus sham stimulation was applied each during a 15-minute stimulation phase in a within-subject-cross-randomized-design. Mean oxygenation of the PFC and functional connectivity were assessed using fNIRS. Additionally, heart rate variability (HRV), heart rate (HR), electrodermal activity (EDA), and saliva alpha-amylase (sAA) were assessed to quantify peripheral ANS activity.


      Using linear mixed-effects models, HRV increased (p < .0001) and HR (p < .0001) decreased during tVNS compared to sham. No effect on EDA or sAA was observed. PFC oxygenation increased over time under tVNS compared to sham (p = .017). The relative increase in HRV and decrease in HR was associated with increased oxygenation of the PFC (HR: p < .0001; HRV: p = .007). Exploratory analyses illustrated, that under tVNS, PFC connectivity increased compared to sham.


      The present study supports the NIM by showing that tVNS influences ANS activity and that relative changes in PFC oxygenation contribute to these effects. Implications of these findings and directions for further research are discussed.


      ANS (autonomic nervous system), BDI-II (Beck Depression Inventory), CAN (central autonomous nervous system), CDRS-R (Children's Depression Rating Scale – Revised), CDT (color detection task), CECA.Q (Childhood Experiences of Care and Abuse questionnaire), C-GAS (Children's Global Assessment Scale), CNS (central nervous system), DERS (Difficulties in Emotion Regulation Scale), (dl)PFC ((dorsolateral) prefrontal cortex), ECG (electrocardiography), EDA (electrodermal activity), (f)NIRS ((functional) near-infrared spectroscopy), HR(V) (heart rate (variability)), IBI (inter-beat interval), iSCR (integrated skin conductance response), mPFC (medial prefrontal cortex), NVM (neurovisceral integration model), PIN (positive intrinsic negative), rMSSD (Root Mean Square of Successive Differences), ROI (region of interest), sAA (saliva alpha-amylase), SCID-II (Structured Clinical Interview for DSM-IV Personality Disorders), SITBI-G (Self-Injurious Thoughts and Behaviors interview), TTH (tension type headache), (t)VNS ((transcutaneous) vagus nerve stimulation)


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