Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review

Abstract

Background: Electrical stimulation of the auricular branch of the vagus nerve (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with inconsistent findings due to variability in stimulation targets and parameters.

Objective: We developed a taVNS/fMRI system to enable concurrent electrical stimulation and fMRI acquisition to compare the effects of taVNS in relation to control stimulation.

Methods: We enrolled 17 healthy adults in this single-blind, crossover taVNS/fMRI trial. Based on parameters shown to affect heart rate in healthy volunteers, participants received either left tragus (active) or earlobe (control) stimulation at 500 μs 25 HZ for 60 s (repeated 3 times over 6 min). Whole brain fMRI analysis was performed exploring the effect of: active stimulation, control stimulation, and the comparison. Region of interest analysis of the midbrain and brainstem was also conducted.

Results: Active stimulation produced significant increased BOLD signal in the contralateral postcentral gyrus, bilateral insula, frontal cortex, right operculum, and left cerebellum. Control stimulation produced BOLD signal activation in the contralateral postcentral gyrus. In the active vs. control contrast, tragus stimulation produced significantly greater BOLD increases in the right caudate, bilateral anterior cingulate, cerebellum, left prefrontal cortex, and mid-cingulate.

Conclusion: Stimulation of the tragus activates the cerebral afferents of the vagal pathway and combined with our review of the literature suggest that taVNS is a promising form of VNS. Future taVNS/fMRI studies should systematically explore various parameters and alternative stimulation targets aimed to optimize this novel form of neuromodulation.

Keywords: Anterior cingulate cortex (ACC); Ear stimulation; Transcutaneous auricular vagus nerve stimulation (taVNS); fMRI.

Fig. 1.. Afferent pathway of the vagus nerve and regions activated by taVNS/fMRI studies.

Areas of the brain involved in the afferent vagal pathway. Nucleus tractus solitarius (NTS), locus coeruleus (LC), cerebellum (CB) thalamus (Thal), hypothalamus (Hyp), amygdala (Amg), and nucleus basalis (NBM) orbital frontal cortex (OFC), cingulate cortex (Cing), and prefrontal cortex (PFC). Effects are not limited to the named structures, as there are unlisted widespread, diffuse cortical effects (Cortex). Numbers labelling relevant regions of brain activations determined by corresponding study listed in adjacent table.

Fig. 2.. Imaging study design.

a) Overview of scanning visits and MRI scans acquired. b) Block design of the concurrent taVNS/fMRI BOLD scans with stimulation times for “ON” and “OFF” blocks. c) Ear stimulation targets.

Fig. 3.. taVNS/fMRI system overview.

a) picture of final taVNS electrodes that have been 3d printed and assembled b) CAD drawings of electrodes demonstrating the 3-piece design and “U” shaped spring clip. Ag/AgCl electrodes were affixed to the inside part of the electrode clips. c) Overview of how taVNS is synchronized and delivered to the participant in the fMRI scanner. Timing is driven from the console computer. Triggering of the direct current stimulator occurs in the equipment room which propagates an electrical stimulation current through a grounded RF filter and into the magnet room through a 10 m cable that attaches to the participant's ear in the scanner.

Fig. 4.. Control and active stimulation findings.

a) Control stimulation only fMRI BOLD activations (compared to rest). (n = 17, one sample t-test, cluster FEW p < .05, cluster forming threshold p < .005, extent threshold = 100 voxels). b) Tragus stimulation only fMRI BOLD activations (compared to rest) (n = 17, one sample t-test, cluster FWE p < .05, cluster forming threshold p < .005, extent threshold = 100 voxels).

Fig. 5.. Active stimulation > control stimulation findings.

fMRI BOLD activations resulting from the contrast active > control stimulation only. (n = 17, paired sample t-test, cluster FWE p < .05, cluster forming threshold p < .005, extent threshold = 100 voxels).