Transcutaneous Auricular Vagus Nerve Stimulation for Visually Induced Motion Sickness: An eLORETA Study

Abstract

Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive form of electrical brain stimulation, has shown potent therapeutic potential for a wide spectrum of conditions. How taVNS influences the characterization of motion sickness - a long mysterious syndrome with a polysymptomatic onset - remains unclear. Here, to examine taVNS-induced effects on brain function in response to motion-induced nausea, 64-channel electroencephalography (EEG) recordings from 42 healthy participants were analyzed; collected during nauseogenic visual stimulation concurrent with taVNS administration, in a crossover randomized sham-controlled study. Cortical neuronal generators were estimated from the obtained EEG using exact low-resolution brain electromagnetic tomography (eLORETA). While both sham and taVNS increased insula activation during electrical stimulation, compared to baseline, taVNS additionally augmented middle frontal gyrus neuronal activity. Following taVNS, brain regions including the supramarginal, parahippocampal, and precentral gyri were activated. Contrasting sham, taVNS markedly increased activity in the middle occipital gyrus during stimulation. A repeated-measures ANOVA showed that taVNS reduced motion sickness symptoms. This reduction in symptoms correlated with taVNS-induced neural activation. Our findings provide new insights into taVNS-induced brain changes, during and after nauseogenic stimuli exposure, including accompanying behavioral response. Together, these findings suggest that taVNS has promise as an effective neurostimulation tool for motion sickness management.

Keywords: Electroencephalography; Motion sickness; Source localization; Transcutaneous auricular vagus nerve stimulation; eLORETA.

Fig. 1

Experimental design and timeline schematics. Participants underwent a pre-screening process which included completion of the motion sickness susceptibility questionnaire (MSSQ). Thereafter, participants were randomized to receive sham or taVNS for their first visit (Visit 1), then receive opposite treatment at 1-week follow-up (Visit 2). On the day of the experiment, participants completed a pre and post motion sickness assessment questionnaire (MSAQ) and simulator sickness questionnaire (SSQ); additionally, participants underwent a baseline period, followed by nauseogenic visual stimulation in synchrony with electrical stimulation, then a recovery period, while electroencephalogram (EEG) signals were recorded

Fig. 2

(a) Box plot showing MSSQ-Short raw scores of MSA and MSB for all participants. Solid lines indicate mean; dashed lines indicate median. (b) Spearman correlation between MSA and MSB where each data point represents a participant (Spearman $\rho$ = 0.35). MSSQ, motion sickness susceptibility questionnaire; MSA, below 12 years of age MSSQ scores; MSB, over the last 10 years MSSQ scores

Fig. 3

eLORETA of Sham versus Baseline, and Post-Sham versus Baseline contrasts. (a) Changes in estimated source activity (delta) between Sham (i.e., during stimulation period) and Baseline were identified in the right insula (BA 13, peak MNI_x,y,z= 35 -20 20, t = 7.83). (b) Estimated source activity (alpha) differences between Post-Sham and Baseline were identified at the right middle frontal gyrus (BA 9, peak MNI_x,y,z= 45 30 40, t = 5.70). Slice views of source locations from left to right are axial, coronal, and sagittal images; viewed from top, back, and right. In all of the images, the left side of the brain is shown on the left. BA, Brodmann area

Fig. 4

eLORETA of taVNS versus Baseline contrast. (a) Differential estimated source activity (delta) at the right insula (BA 13, peak MNI_x,y,z= 35 -20 15, t = 5.96). (b) Changes in source activity (theta) observed at the left middle frontal gyrus (BA 46, peak MNI_x,y,z= -45 35 20, t = 5.47). Slice views of source locations from left to right are axial, coronal, and sagittal images; viewed from top, back, and right. In all of the images, the left side of the brain is shown on the left. BA, Brodmann area

Fig. 5

eLORETA of active Post-taVNS versus Baseline contrast. (a) Following taVNS, increased estimated source activity was observed at the supramarginal gyrus (BA 40, peak MNI_x,y,z= -40 -50 35, t = 4.53) for delta, (b) the middle frontal gyrus (BA 6, peak MNI_x,y,z= 40 0 45, t = 3.84) for theta, (c) the parahippocampal gyrus (BA 35, peak MNI_x,y,z= 20 -25 -15, t = 4.62) for alpha, (d) and the precentral gyrus (BA 6, peak MNI_x,y,z= -55 -5 50, t = 3.98) for gamma. Slice views of source locations from left to right are axial, coronal, and sagittal images; viewed from top, back, and right. In all of the images, the left side of the brain is shown on the left. taVNS, transcutaneous auricular vagus nerve stimulation; BA, Brodmann area

Fig. 6

eLORETA of active taVNS versus Sham contrast. Differential source activity of theta oscillation was observed at the left middle occipital gyrus (BA 19, peak MNI_x,y,z= -50 -60 -10, t = 3.97). Slice views of source locations from left to right are axial, coronal, and sagittal images; viewed from top, back, and right. In all of the images, the left side of the brain is shown on the left. taVNS, transcutaneous auricular vagus nerve stimulation; BA, Brodmann area

Fig. 7

(a) Scatter plots show that the change in activation of the left middle occipital gyrus (L.MOG) between sham and taVNS stimulation was positively associated with MSA responses (Pearson r $=0.43$), (b) and correlated with the change in SSQ total scores (Spearman $\rho$ $=0.35$). MSSQ, motion sickness susceptibility questionnaire; MSA, below 12 years of age MSSQ scores; SSQ, simulator sickness questionnaire