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.
Highlights
The olfactory system plays a fundamental role in our interactions with the environment, from detecting hazards to determining food consumption (Doty, 2012; Huart et al, 2013)
There was no significant difference in the performance of the Odor Threshold Test (OTT) after vagus nerve stimulation (VNS) stimulation under any of the three stimulation parameters [high frequency VNS, p = 0.523 (Wilcoxon signed-rank test); low frequency VNS, p = 0.186; placebo stimulation, p = 0.904]
In the near-infrared spectroscopy (NIRS) recording of the orbitofrontal cortex (OFC) in the left and right hemispheres during the OTT, there were no significant differences in venous-weighted percent of rSO2 (VWrSO2) (%) under all three stimulation parameters in all three stages of the experiment (Pre-S, S, Post-S)
Summary
The olfactory system plays a fundamental role in our interactions with the environment, from detecting hazards to determining food consumption (Doty, 2012; Huart et al, 2013). Interconnected olfactory areas are responsible for various processes of the central nervous system in relation to smell, including memory (Velayudhan et al, 2013), spatial navigation (Alves et al, 2014), pleasure, mood and sensation (Sobel et al, 2003; Katata et al, 2009). The olfactory tract projects to the primary olfactory (cerebral) centers which includes the entorhinal cortex, piriform cortex and the parahippocampal gyrus, and to the secondary olfactory (cerebral) centers which includes the hypothalamus, thalamus and the orbitofrontal cortex (OFC) (Savic et al, 2000; Sobel et al, 2003; Katata et al, 2009). An integral component of the olfactory system, the OFC, functions as the main neocortical projection, acting as a relay station for all arriving afferent inputs from numerous olfactory areas and sending feedback (Gottfried, 2006; Patel and Pinto, 2014)
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