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

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 (n = 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 (p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS (p = 0.014, post-hoc with Bonferroni correction) 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.

Systematic review of olfactory shifts related to obesity

“…Vagal effects on olfaction have been previously demonstrated in both animal and human studies. Indeed, stimulation of the vagus nerve has been shown to improve olfactory functioning in both animals and humans . By contrast, vagal injuries can cause temporal sensory deficits for up to 12 months (both gustatory and olfactory), as observed by Harris and Griffin in patients who underwent oesophagectomies or subtotal/total gastrectomies.…”

Non-invasive High Frequency Median Nerve Stimulation Effectively Suppresses Olfactory Intensity Perception in Healthy Males

“…In the current literature, low frequency MNS has indicated several functions in regards to gastric mobility that includes accelerated gastric emptying of liquids and improved gastric slow-wave rhythmicity (Ouyang et al, 2002), effects absent after vagotomy (Noguchi and Hayashi, 1996; Xu et al, 2006). In a previous article by our group (Maharjan et al, 2018), non-invasive and high frequency auricular VN electrostimulation improved olfactory performance in the supra-threshold test. This indicated that high frequency, VN stimulation (VNS) can modulate olfactory function with its neural connections (Figure 5).…”

“…This is the first study that indicates that MNS under high frequency stimulation can suppress odor intensity ratings of specific concentrations of several odors in combination with the increased and simultaneous activation in the OFCs in both hemispheres. The previous study by our group (Maharjan et al, 2018) demonstrated that non-invasive high frequency (80 Hz) electrostimulation of the auricular VN can improve the performance of supra-threshold test in healthy, adult male participants. This improvement in supra-threshold olfactory function was also supported by a significant improvement of VWrSO 2 (%) in the NIRS recordings only in the right hemisphere (Maharjan et al, 2018).…”

“…The previous study by our group (Maharjan et al, 2018) demonstrated that non-invasive high frequency (80 Hz) electrostimulation of the auricular VN can improve the performance of supra-threshold test in healthy, adult male participants. This improvement in supra-threshold olfactory function was also supported by a significant improvement of VWrSO 2 (%) in the NIRS recordings only in the right hemisphere (Maharjan et al, 2018). In the present study, high frequency electrostimulation (80 Hz) of the MN suppressed the supra-threshold function of odor intensity ratings in the healthy volunteers with the bilateral improvement of VWrSO 2 (%) in the NIRS recordings in both hemispheres.…”

“…In a previous article by our group (Maharjan et al, 2018), non-invasive and high frequency auricular VN electrostimulation improved olfactory performance in the supra-threshold test. However, to date, the MNS’ potential effects on olfactory function via its interactions with vagal nerve networks has not been explored yet.…”