Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans

Overview

Journal Front Neurosci

Date 2018 May 10

PMID 29740266

Citations 8

Authors

Ashim Maharjan

Eunice Wang

Mei Peng

Yusuf O Cakmak

Affiliations

Soon will be listed here.

Abstract

In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants ( = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT ( = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS ( = 0.014, with ) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort.

Citing Articles

Transcutaneous Vagus Nerve Stimulation Effects on Flavor-Evoked Electroencephalogram and Eye-Blink Rate.

Albayrak S, Aydin B, Ozen G, Yalcin F, Balik M, Yanik H Brain Behav. 2025; 15(3):e70355.

PMID: 40079485 PMC: 11904970. DOI: 10.1002/brb3.70355.

Transcutaneous vagus nerve stimulation for Parkinson's disease: a systematic review and meta-analysis.

Shan J, Li Z, Ji M, Zhang M, Zhang C, Zhu Y Front Aging Neurosci. 2025; 16:1498176.

PMID: 39877075 PMC: 11772336. DOI: 10.3389/fnagi.2024.1498176.

Association between perceived olfactory dysfunction and all-cause mortality in Chinese adults: A prospective community-based study.

Zhang Z, Liu Y, Li Y, Geng T, Chen S, Wu S J Glob Health. 2024; 14:04237.

PMID: 39545350 PMC: 11565469. DOI: 10.7189/jogh.14.04237.

Transcutaneous auricular vagus nerve stimulation alters cough sensitivity depending on stimulation parameters: potential implications for aspiration risk.

Ng K, Guiu Hernandez E, Haszard J, Macrae P, Huckabee M, Cakmak Y Front Neurosci. 2024; 18:1265894.

PMID: 38406583 PMC: 10885700. DOI: 10.3389/fnins.2024.1265894.

fNIRS neuroimaging in olfactory research: A systematic literature review.

Gunasekara N, Gaeta G, Levy A, Boot E, Tachtsidis I Front Behav Neurosci. 2023; 16:1040719.

PMID: 36620865 PMC: 9815777. DOI: 10.3389/fnbeh.2022.1040719.

References

Doty R, Smith R, McKeown D, Raj J . Tests of human olfactory function: principal components analysis suggests that most measure a common source of variance. Percept Psychophys. 1994; 56(6):701-7. DOI: 10.3758/bf03208363. View

Higami T, Kozawa S, Asada T, Obo H, Gan K, Iwahashi K . Retrograde cerebral perfusion versus selective cerebral perfusion as evaluated by cerebral oxygen saturation during aortic arch reconstruction. Ann Thorac Surg. 1999; 67(4):1091-6. DOI: 10.1016/s0003-4975(99)00135-6. View

Desikan R, McEvoy L, Thompson W, Holland D, Brewer J, Aisen P . Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau. Arch Neurol. 2012; 69(6):709-13. PMC: 3423526. DOI: 10.1001/archneurol.2011.3354. View

Murphy C, Schubert C, Cruickshanks K, Klein B, Klein R, Nondahl D . Prevalence of olfactory impairment in older adults. JAMA. 2002; 288(18):2307-12. DOI: 10.1001/jama.288.18.2307. View

Damian M, Schlosser R . Bilateral near infrared spectroscopy in space-occupying middle cerebral artery stroke. Neurocrit Care. 2007; 6(3):165-73. DOI: 10.1007/s12028-007-0010-3. View

Karow D, McEvoy L, Fennema-Notestine C, Hagler Jr D, Jennings R, Brewer J . Relative capability of MR imaging and FDG PET to depict changes associated with prodromal and early Alzheimer disease. Radiology. 2010; 256(3):932-42. PMC: 2923729. DOI: 10.1148/radiol.10091402. View

Duffy V, Backstrand J, Ferris A . Olfactory dysfunction and related nutritional risk in free-living, elderly women. J Am Diet Assoc. 1995; 95(8):879-84; quiz 885-6. DOI: 10.1016/S0002-8223(95)00244-8. View

Wayner M . Vagus nerve stimulation modifies the electrical activity of the olfactory bulb. Brain Res Bull. 1984; 12(5):529-37. DOI: 10.1016/0361-9230(84)90168-0. View

De Letter J, Sie T, Moll F, Algra A, Eikelboom B, Ackerstaff G . Transcranial cerebral oximetry during carotid endarterectomy: agreement between frontal and lateral probe measurements as compared with an electroencephalogram. Cardiovasc Surg. 1998; 6(4):373-7. DOI: 10.1016/s0967-2109(98)00020-9. View

10.

Mulazimoglu S, Flury R, Kapila S, Linder T . Effects of a sensory branch to the posterior external ear canal: coughing, pain, Ramsay Hunt's syndrome and Hitselberger's sign. J Laryngol Otol. 2017; 131(4):329-333. DOI: 10.1017/S0022215117000160. View

11.

Doty R, McKeown D, Lee W, Shaman P . A study of the test-retest reliability of ten olfactory tests. Chem Senses. 1995; 20(6):645-56. DOI: 10.1093/chemse/20.6.645. View

12.

Ikemoto S . Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev. 2007; 56(1):27-78. PMC: 2134972. DOI: 10.1016/j.brainresrev.2007.05.004. View

13.

Bohning D, Lomarev M, Denslow S, Nahas Z, Shastri A, George M . Feasibility of vagus nerve stimulation-synchronized blood oxygenation level-dependent functional MRI. Invest Radiol. 2001; 36(8):470-9. DOI: 10.1097/00004424-200108000-00006. View

14.

Powell T, Cowan W, Raisman G . The central olfactory connexions. J Anat. 1965; 99(Pt 4):791-813. PMC: 1270719. View

15.

Madsen P, Skak C, Rasmussen A, Secher N . Interference of cerebral near-infrared oximetry in patients with icterus. Anesth Analg. 2000; 90(2):489-93. DOI: 10.1097/00000539-200002000-00046. View

16.

Gervais R . Unilateral lesions of the olfactory tubercle modifying general arousal effects in the rat olfactory bulb. Electroencephalogr Clin Neurophysiol. 1979; 46(6):665-74. DOI: 10.1016/0013-4694(79)90104-4. View

17.

Cakmak Y, Apaydin H, Kiziltan G, Gunduz A, Ozsoy B, Olcer S . Rapid Alleviation of Parkinson's Disease Symptoms via Electrostimulation of Intrinsic Auricular Muscle Zones. Front Hum Neurosci. 2017; 11:338. PMC: 5487461. DOI: 10.3389/fnhum.2017.00338. View

18.

Harada H, Tanaka M, Kato T . Brain olfactory activation measured by near-infrared spectroscopy in humans. J Laryngol Otol. 2006; 120(8):638-43. DOI: 10.1017/S002221510600123X. View

19.

Guevara-Guzman R, Wayner M, Armstrong D . Role of the paraventricular nucleus in the projection from the nucleus of the solitary tract to the olfactory bulb. Brain Res Bull. 1991; 27(3-4):447-50. DOI: 10.1016/0361-9230(91)90140-f. View

20.

Jones-Gotman M, Zatorre R . Odor recognition memory in humans: role of right temporal and orbitofrontal regions. Brain Cogn. 1993; 22(2):182-98. DOI: 10.1006/brcg.1993.1033. View