The Effect of Auricular Vagus Nerve Stimulation on Heart Rate Variability

Year 2025, Issue: 26, 771 - 783, 31.08.2025

Gülşah Konakoğlu , Ayşem Ecem Özdemir , Öznur Kaya Sağlam , Büşra Sayir

https://doi.org/10.38079/igusabder.1660696

Abstract

Autonomic nervous system (ANS) is a structure which operates involuntarily and controls vital functions. Vagus Nerve Stimulation (VNS) is a novel treatment method focused on addressing ANS dysfunctions in cases of imbalance between sympathetic and parasympathetic nervous system activation. With VNS, parasympathetic activity (PA) increases while sympathetic activity (SA) decreases, affecting cardiovascular parameters. Heart rate fluctuates with each beat, reflecting the influence of PA and SA signals on the sinoatrial node. Research indicates that as individuals age, PA in the heart diminishes, while SA tone increases. When heart rate variability (HRV) and respiratory sinus arrhythmia are used to assess vagal tone, reduced PA control over the heart is revealed. This shift in autonomic balance is linked to a higher risk of developing cardiovascular disease. Therefore, it is important to consider the restoration of this balance as a therapeutic goal. Heart rate variability is the most used method for evaluating ANS functions. In this review, studies investigating the effect of auricular VNS on HRV are evaluated. It has been observed that there is a need for research investigating the short- and long-term effects of stimulations performed with different parameters from different ears on cardiovascular parameters in healthy individuals and/or individuals with various clinical conditions. Thus, a more specific and effective use of auricular VNS for different clinical situations can be achieved.

Keywords

Auricular vagus nerve stimulation , heart rate variability , autonomic dysfunction

Auriküler Vagus Sinir Uyarımının Kalp Hızı Değişkenliği Üzerindeki Etkisi

Abstract

Otonom sinir sistemi (OSS), istemsiz olarak çalışan ve hayati fonksiyonları kontrol eden bir yapıdır. Vagus Sinir Uyarımı (VSU), sempatik ve parasempatik sinir sistemi aktivasyonu arasındaki dengesizlik durumlarında OSS işlev bozukluklarını ele almaya odaklanan yeni bir tedavi yöntemidir. VSU ile parasempatik aktivite (PA) artarken sempatik aktivite (SA) azalır ve bu durum kardiyovasküler parametreleri etkiler. Kalp hızı her atışta dalgalanır ve dolayısıyla PA ve SA sinyallerinin sinoatriyal düğüm üzerindeki etkisini yansıtır. Araştırmalar, bireyler yaşlandıkça kalpteki PA tonunun azaldığını, SA tonunun ise arttığını göstermektedir. Vagal tonu değerlendirmek için kalp hızı değişkenliği (KHD) ve solunum sinüs aritmisi kullanıldığında, PA'nın kalp üzerindeki kontrolünde bir düşüş gösterirler. Otonom dengedeki bu değişim, kardiyovasküler hastalık geliştirme riskinin artmasıyla bağlantılıdır. Bu nedenle, bu dengenin yeniden sağlanmasını terapötik bir hedef olarak düşünmek önemlidir. Kalp hızı değişkenliği, OSS fonksiyonlarını değerlendirmek için en çok kullanılan yöntemdir. Bu derlemede, auriküler VSU'nun HRV üzerindeki etkisini araştıran çalışmalar değerlendirilmiştir. Sağlıklı bireylerde ve/veya çeşitli klinik rahatsızlıkları olan bireylerde, farklı kulaklardan farklı parametrelerle yapılan uyarımların kardiyovasküler parametreler üzerindeki kısa ve uzun vadeli etkilerini araştıran araştırmalara ihtiyaç olduğu gözlemlenmiştir. Böylece, farklı klinik durumlar için auriküler VSU'nun daha spesifik ve etkili bir şekilde kullanılması sağlanabilir.

Keywords

Auriküler vagus sinir uyarımı , kalp hızı değişkenliği , otonomik disfonksiyon

References

• 1. Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis. Frontiers in Neuroscience. 2018;12:336-468. doi: 10.3389/fnins.2018.00049.
• 2. Yuan H, Silberstein S. Vagus nerve and vagus nerve stimulation, a comprehensive review: part I. Headache: The Journal of Head and Face Pain. 2015;56(1):71-78.
• 3. Buturak V, Bakar B. A new therapy modality for treatment-resistant depression: Vagal nerve stimulation. Journal of Mood Disorders. 2014;4(4):167-74.
• 4. Butt M, Albusoda A, Farmer A, Aziz Q. The anatomical basis for transcutaneous auricular vagus nerve stimulation. Journal of Anatomy. 2020;236(4):588-611.
• 5. LeBouef T, Yaker Z, Whited L. Physiology, autonomic nervous system. In: StatPearls [Internet]. StatPearls Publishing, 2023.
• 6. Grassi G, Bombelli M, Seravalle G, Dell'Oro R, Quarti-Trevano F. Diurnal blood pressure variation and sympathetic activity. Hypertension Research. 2010;33(5):381-385.
• 7. Deuchars SA, Lall VK. Sympathetic preganglionic neurons: Properties and inputs. Comprehensive Physiology. 2015;5(2):829-869. doi: 10.1002/cphy.c140020.
• 8. Lall VK, Bruce G, Voytenko L, et al. Physiologic regulation of heart rate and blood pressure involves connexin 36–containing gap junctions. The FASEB Journal. 2017;31(9):3966-77.
• 9. Deuchars SA, Lall VK, Clancy J, et al. Mechanisms underpinning sympathetic nervous activity and its modulation using transcutaneous vagus nerve stimulation. Experimental Physiology. 2018;103(3):326-331. doi: 10.1113/EP086433.
• 10. Malliani A. Heart rate variability: from bench to bedside. European Journal of Internal Medicine. 2005;16(1):12-20. doi: 10.1016/j.ejim.2004.06.016.
• 11. De Meersman RE, Stein PK. Vagal modulation and aging. Biological Psychology. 2007;74(2):165-173. doi: 10.1016/j.biopsycho.2006.04.008.
• 12. Abhishekh HA, Nisarga P, Kisan R, et al. Influence of age and gender on autonomic regulation of heart. Journal of Clinical Monitoring and Computing. 2013;27:259-264.
• 13. He B, Lu Z, He W, Huang B, Jiang H. Autonomic modulation by electrical stimulation of the parasympathetic nervous system: an emerging intervention for cardiovascular diseases. Cardiovascular Therapeutics. 2016;34(3):167-171.
• 14. Byku M, Mann DL. Neuromodulation of the failing heart: lost in translation? JACC: Basic to Translational Science. 2016;1(3):95-106. doi: 10.1016/j.jacbts.2016.03.004.
• 15. Task Force of the European Society of Cardiology the North American Society of Pacing Electrophysiology, Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation. 1996;93(5):1043–1065.
• 16. McCraty R, Shaffer F. Heart rate variability: new perspectives on physiological mechanisms, assessment of self-regulatory capacity, and health risk. Global Advances in Health And Medicine. 2015;4(1):46–61. doi: 10.7453/gahmj.2014.073.
• 17. Shaffer F, McCraty R, Zerr CL. A healthy heart is not a metronome: An integrative review of the heart's anatomy and heart rate variability. Frontiers in Psychology. 2014;5:1040.
• 18. Gevirtz RN, Lehrer PM, Schwartz MS. Cardiorespiratory biofeedback. Biofeedback: A Practitioner’s Guide, The Guilford Press, New York, USA. 2016;196-213.
• 19. Hayano J. Part II: Heart rate variability. Clinical Assesment of the Autonomic Nervous System. Japan, Springer. 2017;109-127.
• 20. Goldberger AL. Is the normal heartbeat chaotic or homeostatic? News in Physiological Sciences. 1991;6:87–91. doi: 10.1152/physiologyonline.1991.6.2.87.
• 21. Beckers F, Verheyden B, Aubert AE. Aging and nonlinear heart rate control in a healthy population. American Journal of Physiology-Heart and Circulatory Physiology. 2006;290(6):H2560–H2570. doi: 10.1152/ajpheart.00903.2005.
• 22. Zygmunt A, Stanczyk J. Methods of evaluation of autonomic nervous system function. Archives of Medical Science. 2010;6(1):11-18. doi: 10.5114/aoms.2010.13500.
• 23. Kleiger RE, Stein PK, Bigger JT Jr. Heart rate variability: measurement and clinical utility. Annals of Noninvasive Electrocardiology. 2005;10(1):88-101.
• 24. Laborde S, Mosley E, Thayer JF. Heart rate variability and cardiac vagal tone in psychophysiological research - recommendations for experiment planning, data analysis, and data reporting. Frontiers in Psychology. 2017;8:213. doi: 10.3389/fpsyg.2017.00213.
• 25. Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Frontiers in Public Health. 2017;5:258. doi: 10.3389/fpubh.2017.00258.
• 26. Nunan D, Sandercock GR, Brodie DA. A quantitative systematic review of normal values for short‐term heart rate variability in healthy adults. Pacing and Clinical Electrophysiology. 2010;33(11):1407-1417. doi: 10.1111/j.1540-8159.2010.02841.x.
• 27. Cakir A, Alptekin K, Özden A, Öncü J. Immediate effects of chiropractic thoracic manipulations on the autonomic nervous system. J. Orthop. Trauma Surg. Relat. Res. 2019;14(3):7-14.
• 28. Tarvainen MP, Lipponen J, Niskanen JP, Ranta-Aho P. Kubios HRV Version 3- User’s Guide. Kuopio, University of Eastern Finland, 2017.
• 29. Aras D, Erdoğmuş TN, Ayvaz Ö, Birol A. Kalp hızı değişkenliği ve egzersize kronik yanıtları. SPORMETRE The Journal of Physical Education and Sport Sciences. 2022;20(4):1-40.
• 30. Kuusela T. Methodological aspects of heart rate variability analysis. Heart Rate Variability (HRV) Signal Analysis. CRC Press, Florida, USA, 2013.
• 31. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. The American Journal of Cardiology. 1987;59(4): 256–262. doi: 10.1016/0002-9149(87)90795-8.
• 32. Baek HJ, Cho CH, Cho J, Woo JM. Reliability of ultra-short-term analysis as a surrogate of standard 5-min analysis of heart rate variability. Telemedicine Journal and E-Health. 2015;21(5):404–414. doi: 10.1089/tmj.2014.0104.
• 33. Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. Journal of the American College of Cardiology. 1998;31(3):593–601.
• 34. Otzenberger H, Gronfier C, Simon C, et al. Dynamic heart rate variability: A tool for exploring sympathovagal balance continuously during sleep in men. The American Journal of Physiology. 1998;275(3):946–950.
• 35. DeGiorgio CM, Miller P, Meymandi S. RMSSD, a measure of vagus-mediated heart rate variability, is associated with risk factors for SUDEP: The SUDEP-7 Inventory. Epilepsy & Behavior. 2010;19(1):78–81.
• 36. Bigger JT Jr, Fleiss JL, Steinman RC, Rolnitzky LM, Kleiger RE, Rottman JN. Frequency domain measures of heart period variability and mortality after myocardial infarction. Circulation. 1992;85(1):164-71. doi: 10.1161/01.CIR.85.1.164.
• 37. Shah AJ, Lampert R, Goldberg J, Veledar E, Bremner JD, Vaccarino V. Posttraumatic stress disorder and impaired autonomic modulation in male twins. Biological Psychiatry. 2013;73:1103-10. doi: 10.1016/j.biopsych.2013.01.019.
• 38. Lampert R, Bremner JD, Su S, et al. Decreased heart rate variability is associated with higher levels of inflammation in middle-aged men. American Heart Journal. 2008,156:759.e1-7.
• 39. Theorell T, Liljeholm-Johansson Y, Björk H, Ericson M. Saliva testosterone and heart rate variability in the professional symphony orchestra after “public faintings” of an orchestra member. Psychoneuroendocrinology. 2007;32:660-8.
• 40. Taylor JA, Carr DL, Myers CW, Eckberg DL. Mechanisms underlying very-low-frequency RR-interval oscillations in humans. Circulation. 1998;98:547-55.
• 41. Berntson GG, Bigger JT Jr, Eckberg DL, et al. Heart rate variability: Origins, methods, and interpretive caveats. Psychophysiology. 1997;34:623-48.
• 42. Ahmed AK, Harness JB, Mearns AJ. Respiratory control of heart rate. European Journal of Applied Physiology. 1982;50:95-104. doi: 10.1007/BF00952248.
• 43. Lehrer PM, Vaschillo E, Vaschillo B, et al. Heart rate variability biofeedback increases baroreflex gain and peak expiratory flow. Psychosomatic Medicine. 2003;65(5):796–805.
• 44. Brown TE, Beightol LA, Koh J, Eckberg DL. Important influence of respiration on human RR interval power spectra is largely ignored. Journal Applied Physiology. 1985;5:2310-7.
• 45. Tiller WA, McCraty R, Atkinson M. Cardiac coherence: A new, noninvasive measure of autonomic nervous system order. Alternative Therapies in Health and Medicine. 1996;2(1):52-65.
• 46. Grossman P, Taylor EW. Toward understanding respiratory sinus arrhythmia: Relations to cardiac vagal tone, evolution and biobehavioral functions. Biological Psychology. 2007;74:263-85. doi: 10.1016/j.biopsycho.2005.11.014.
• 47. Eckberg DL, Eckberg MJ. Human sinus node responses to repetitive, ramped carotid baroreceptor stimuli. The American Journal of Physiology. 1982;242(4):638–644.
• 48. Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. International Journal of Cardiology. 2010;141:122-31. doi: 10.1016/j.ijcard.2009.09.543.
• 49. Egizio VB, Eddy M, Robinson M, Jennings JR. Efficient and cost-effective estimation of the influence of respiratory variables on respiratory sinus arrhythmia. Psychophysiology. 2011;48:488-94. doi: 10.1111/j.1469-8986.2010.01086.x.
• 50. Kember GC, Fenton GA, Armour JA, Kalyaniwalla N. Competition model for aperiodic stochastic resonance in a Fitzhugh-Nagumo model of cardiac sensory neurons. Phys Rev E Stat Nonlin Soft Matter Phys. 2001;63:041911. doi: 10.1103/PhysRevE.63.041911.
• 51. Stein PK, Reddy A. Non-linear heart rate variability and risk stratification in cardiovascular disease. Indian Pacing And Electrophysiology Journal. 2005;5(3):210–20.
• 52. De Godoy MF. Nonlinear analysis of heart rate variability: A comprehensive review. Journal of Cardiology and Therapy. 2016;3:528-533.
• 53. Machhada A, Trapp S, Marina N, et al. Vagal determinants of exercise capacity. Nature Communications. 2017;8(1):15097. doi: 10.1038/ncomms15097.
• 54. Stanley J, Peake JM, Buchheit M. Cardiac parasympathetic reactivation following exercise: Implications for training prescription. Sports Medicine. 2013;43(12):1259–1277.
• 55. Malliani A, Montano N. Antihypertensive treatment and sympathetic excitation. Hypertension. 2005;46(3):e8-e8. doi: 10.1161/01.hyp.0000176234.17554.c0.
• 56. Pal G, Pal P, Lalitha V, Dutta T, Adithan C, Nanda N. Sympathovagal imbalance in young prehypertensives: Importance of male-female difference. The American Journal of the Medical Sciences. 2013;345(1):10-17. doi: 10.1097/maj.0b013e31824ba080.
• 57. Clancy J, Mary D, Witte K, Greenwood J, Deuchars S, Deuchars J. Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimulation. 2014;7(6):871-877. doi: 10.1016/j.brs.2014.07.031.
• 58. De Couck M, Cserjesi R, Caers R, et al. Effects of short and prolonged transcutaneous vagus nerve stimulation on heart rate variability in healthy subjects. Autonomic Neuroscience. 2017;203:88-96. doi: 10.1016/j.autneu.2016.11.003.
• 59. Antonino D, Teixeira AL, Maia-Lopes PM, et al. Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial. Brain Stimulation. 2017;10(5):875-881.
• 60. Billman GE. The LF/HF ratio does not accurately measure cardiac sympatho-vagal balance. Front Physiol. 2013;4:26. doi: 10.3389/fphys.2013.00026.
• 61. Sclocco R, Garcia RG, Kettner NW, et al. The influence of respiration on brainstem and cardiovagal response to auricular vagus nerve stimulation: a multimodal ultrahigh-field (7T) fMRI study. Brain Stimulation. 2019;12(4):911-921. doi: 10.1016/j.brs.2019.02.003.
• 62. Machetanz K, Berelidze L, Guggenberger R, Gharabaghi A. Brain–heart interaction during transcutaneous auricular vagus nerve stimulation. Front. Neurosci. 2021;15:632697.
• 63. Thayer JF, Åhs F, Fredrikson M, Sollers III JJ, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: Implications for heart rate variability as a marker of stress and health. Neuroscience & Biobehavioral Reviews. 2012;36(2):747-756.
• 64. Patron E, Mennella R, Benvenuti SM, Thayer JF. The frontal cortex is a heart-brake: Reduction in delta oscillations is associated with heart rate deceleration. Neuroimage. 2019;188:403-410.
• 65. Keute M, Machetanz K, Berelidze L, Guggenberger R, Gharabaghi A. Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects. Brain Stimulation. 2021;14(2):209-216. doi: 10.1016/j.brs.2021.01.001.