Highlights
- •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.
Abstract
Introduction
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).
Methods
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.
Results
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.
Conclusion
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.
Abbreviations:
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)Keywords
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References
- Simultaneous quantitative assessment of cerebral physiology using respiratory-calibrated MRI and near-infrared spectroscopy in healthy adults.NeuroImage. 2014; 85: 255-263https://doi.org/10.1016/j.neuroimage.2013.07.015
- Meeting of minds: the medial frontal cortex and social cognition.Nat. Rev. Neurosci. 2006; 7: 268-277https://doi.org/10.1038/nrn1884
- Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: a concurrent taVNS/fMRI study and review.Brain Stimul. 2018; 11: 492-500https://doi.org/10.1016/j.brs.2017.12.009
- Beck Depression Inventory–II.Harcourt Brace, San Antonio, Texas1996 (Retrieved from)
- A continuous measure of phasic electrodermal activity.J. Neurosci. Methods. 2010; 190: 80-91https://doi.org/10.1016/j.jneumeth.2010.04.028
- Functional and chemical anatomy of the afferent vagal system.Autonomic Neuroscience: Basic and Clinical. 2000; 85: 1-17https://doi.org/10.1016/S1566-0702(00)00215-0
- The vagus nerve at the Interface of the microbiota-gut-brain axis.Front. Neurosci. 2018; 12https://doi.org/10.3389/fnins.2018.00049
- Dynamic causal modelling on infant fNIRS data: a validation study on a simultaneously recorded fNIRS-fMRI dataset.NeuroImage. 2018; 175: 413-424https://doi.org/10.1016/j.neuroimage.2018.04.022
- Transcutaneous vagus nerve stimulation reduces spontaneous but not induced negative thought intrusions in high worriers.Biol. Psychol. 2019; 142: 80-89https://doi.org/10.1016/j.biopsycho.2019.01.014
- The effect of transcutaneous vagus nerve stimulation on fear generalization and subsequent fear extinction.Neurobiol. Learn. Mem. 2019; 161: 192-201https://doi.org/10.1016/j.nlm.2019.04.006
- Moving beyond belief: a narrative review of potential biomarkers for transcutaneous vagus nerve stimulation.Psychophysiology. 2020; 57e13571https://doi.org/10.1111/psyp.13571
- Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity.Brain Stimul. 2014; 7: 871-877https://doi.org/10.1016/j.brs.2014.07.031
- Coping, emotion regulation and psychopathology in childhood and adolescence: a meta-analysis and narrative review.Psychol. Bull. 2017; 143: 939-991https://doi.org/10.1037/bul0000110
- Probing neurovisceral integration via functional near-infrared spectroscopy and heart rate variability.Front. Neurosci. 2020; 14575589https://doi.org/10.3389/fnins.2020.575589
- A systematic comparison of motion artifact correction techniques for functional near-infrared spectroscopy.Front. Neurosci. 2012; 6: 1-10https://doi.org/10.3389/fnins.2012.00147
- Effects of short and prolonged transcutaneous vagus nerve stimulation on heart rate variability in healthy subjects.Auton. Neurosci. 2017; 203: 88-96https://doi.org/10.1016/j.autneu.2016.11.003
- Transcutaneous vagus nerve stimulation modulates default mode network in major depressive disorder.Biol. Psychiatry. 2016; 79: 266-273https://doi.org/10.1016/j.biopsych.2015.03.025
- International consensus based review and recommendations for minimum reporting standards in research on transcutaneous vagus nerve stimulation (Version 2020).Front. Hum. Neurosci. 2021; 14568051https://doi.org/10.3389/fnhum.2020.568051
- The german version of the self-injurious thoughts and behaviors interview (SITBI-G): a tool to assess non-suicidal self-injury and suicidal behavior disorder.BMC Psychiatry. 2014; 14https://doi.org/10.1186/s12888-014-0265-0
- Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: FMRI evidence in humans.Brain Stimul. 2015; 8: 624-636https://doi.org/10.1016/j.brs.2014.11.018
- Heart Rate Variability Analysis with the R package RHRV.Springer International Publishing, Cham2017https://doi.org/10.1007/978-3-319-65355-6
- Sympathetic effect of auricular transcutaneous vagus nerve stimulation on healthy subjects: A crossover controlled clinical trial comparing vagally mediated and active control stimulation using microneurography.Frontiers in Physiology. 2020; 11https://doi.org/10.3389/fphys.2020.599896
- Multidimensional assessment of emotion regulation and dysregulation: development, factor structure, and initial validation of the difficulties in emotion regulation scale.J. Psychopathol. Behav. Assess. 2004; 26: 41-54https://doi.org/10.1023/B:JOBA.0000007455.08539.94
- Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation.Exp. Neurol. 2017; 289: 21-30https://doi.org/10.1016/j.expneurol.2016.12.005
- HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain.Appl. Opt. 2009; 48: 280-298https://doi.org/10.1364/AO.48.00D280
- Report of the committee on methods of clinical examination in electroencephalography: 1957.Electroencephalogr. Clin. Neurophysiol. 1958; 10: 370-375https://doi.org/10.1016/0013-4694(58)90053-1
- Alternate cardiovascular baseline assessment techniques: vanilla or resting baseline.Psychophysiology. 1992; 29: 742-750https://doi.org/10.1111/j.1469-8986.1992.tb02052.x
- Childhood experiences of care and abuse (CECA)—validation of the german version of the questionnaire and interview, and results of an investigation of correlations between adverse childhood experiences and suicidal behaviour.Z. fur Kinder- Jugendpsychiatrie Psychother. 2011; 39: 243-252https://doi.org/10.1024/1422-4917/a000115
- Effects of acute transcutaneous vagus nerve stimulation on emotion recognition in adolescent depression.Psychol. Med. 2019; 1–10https://doi.org/10.1017/S0033291719003490
- Resting state prefrontal cortex oxygenation in adolescent non-suicidal self-injury – a near-infrared spectroscopy study.NeuroImage: Clin. 2021; 31102704https://doi.org/10.1016/j.nicl.2021.102704
- Effects of acute transcutaneous vagus nerve stimulation on emotion recognition in adolescent depression.Psychol. Med. 2021; 51: 511-520https://doi.org/10.1017/S0033291719003490
- Sex differences in healthy human heart rate variability: A meta-analysis.Neurosci. Biobehav. Rev. 2016; 64: 288-310https://doi.org/10.1016/j.neubiorev.2016.03.007
- Near-infrared spectroscopy in schizophrenia: a possible biomarker for predicting clinical outcome and treatment response.Front. Psychiatry. 2013; 4https://doi.org/10.3389/fpsyt.2013.00145
- Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex.Psychiatry Res. Neuroimaging. 2011; 191: 153-159https://doi.org/10.1016/j.pscychresns.2010.11.004
- BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation.J. Neural Transm. 2007; 114: 1485-1493https://doi.org/10.1007/s00702-007-0755-z
- CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal – a pilot study.Brain Stimul. 2013; 6: 798-804https://doi.org/10.1016/j.brs.2013.01.011
- Heart rate variability and cardiac vagal tone in psychophysiological research – recommendations for experiment planning, data analysis, and data reporting.Front. Psychol. 2017; 8https://doi.org/10.3389/fpsyg.2017.00213
- Heart rate variability: standards of measurement, physiological interpretation, and clinical use.Eur. Heart J. 1996; 17: 354-381https://doi.org/10.1093/oxfordjournals.eurheartj.a014868
- The strange case of the ear and the heart: the auricular vagus nerve and its influence on cardiac control.Auton. Neurosci. 2016; 199: 48-53https://doi.org/10.1016/j.autneu.2016.06.004
- Self-injurious thoughts and behaviors interview: development, reliability, and validity in an adolescent sample.Psychol. Assess. 2007; 19: 309-317https://doi.org/10.1037/1040-3590.19.3.309
- Children´s depression rating scale—revised.Psychopharmacol. Bull. 1985; 21: 979-989
- Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults.NeuroImage. 2016; 139: 44-52https://doi.org/10.1016/j.neuroimage.2016.05.076
- A Children’s global assessment scale (C-GAS).Arch. Gen. Psychiatry. 1983; 40: 1228-1231https://doi.org/10.1001/archpsyc.1983.01790100074010
- General equation for the differential pathlength factor of the frontal human head depending on wavelength and age.J. Biomed. Opt. 2013; 18105004https://doi.org/10.1117/1.JBO.18.10.105004
- The mini-international neuropsychiatric interview (M.I.N.I): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.J. Clin. Psychiatry. 1998; 59: 22-33
- Manual for the State-trait Anxiety Inventory (Form Y): (“Self-evaluation Questionnaire”).Consulting Psychologistst Press, Sao Alto, CA1983 (The Netherlands)
- STATA Statistics/Data Analysis (Version 16.0).2019 (College Station, Texas)
- Oxysoft (Version 3.0.103).2016 (The Netherlands)
- Kubios HRV – heart rate variability analysis software.Comput. Methods Prog. Biomed. 2014; 113: 210-220https://doi.org/10.1016/j.cmpb.2013.07.024
- A model of neurovisceral integration in emotion regulation and dysregulation.J. Affect. Disord. 2000; 61: 201-216https://doi.org/10.1016/S0165-0327(00)00338-4
- Claude Bernard and the heart–brain connection: further elaboration of a model of neurovisceral integration.Neurosci. Biobehav. Rev. 2009; 33: 81-88https://doi.org/10.1016/j.neubiorev.2008.08.004
- Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health.Ann. Behav. Med. 2009; 37: 141-153https://doi.org/10.1007/s12160-009-9101-z
- A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health.Neurosci. Biobehav. Rev. 2012; 36: 747-756https://doi.org/10.1016/j.neubiorev.2011.11.009
- MATLAB R2015a.Natick, Massachussetts, United States2015
- Cardiac and peripheral autonomic responses to orthostatic stress during transcutaneous vagus nerve stimulation in healthy subjects.J. Clin. Med. 2019; 8: 496https://doi.org/10.3390/jcm8040496
- A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder.Brain Stimul. 2018; 11: 501-508https://doi.org/10.1016/j.brs.2018.01.006
- Frequency-dependent functional connectivity of the nucleus accumbens during continuous transcutaneous vagus nerve stimulation in major depressive disorder.J. Psychiatr. Res. 2018; 102: 123-131https://doi.org/10.1016/j.jpsychires.2017.12.018
- The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential.Brain Stimul. 2019; 12: 635-642https://doi.org/10.1016/j.brs.2018.12.224
- SKID. Strukturiertes Klinisches Interview für DSM-IV. Achse I und II.(Retrieved from) Handanweisung, 1997
- Does non-invasive vagus nerve stimulation affect heart rate variability? A living and interactive Bayesian meta-analysis.BioRxiv. 2021; 1–29https://doi.org/10.1101/2021.01.18.426704
- Optimization of transcutaneous vagus nerve stimulation using functional MRI.in: Neuromodulation: Technology at the Neural Interface. 20. 2017: 290-300https://doi.org/10.1111/ner.12541
- Non-invasive vagus nerve stimulation reduces sympathetic preponderance in patients with tinnitus.Acta Otolaryngol. 2017; 137: 426-431https://doi.org/10.1080/00016489.2016.1269197
- Vagus nerve and vagus nerve stimulation, a comprehensive review: Part I.Headache. 2016; 56: 71-78https://doi.org/10.1111/head.12647
Article Info
Publication History
Published online: June 13, 2022
Accepted:
June 9,
2022
Received in revised form:
April 20,
2022
Received:
August 20,
2021
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
