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86 reviewsBackground: There is active interest in biomarker discovery for transcutaneous auricular vagus nervestimulation (taVNS). However, greater understanding of the neurobiological mechanisms is needed toidentify candidate markers. Accumulating evidence suggests that taVNS influences activity in solitaryand parabrachial nuclei, the primary brainstem relays for the transmission of visceral sensory afferents tothe insula. The insula mediates interoception, which concerns the representation and regulation ofhomeostatic bodily states. Consequently, interoceptive pathways may be relevant to taVNS mechanismsKeywords:of action.Hypotheses: We hypothesized that taVNS would modulate an EEG-derived marker of interoceptiveTranscutaneousprocessing known as the heart-evoked potential (HEP). We also hypothesized that taVNS-induced HEPAuriculareffects would be localizable to the insula.Vagus nerve stimulationMethods: Using a within-subject, sham-controlled design, we recorded EEG and ECG concurrent toInsulaInteroceptiontaVNS in 43 healthy adults. Using ECG and EEG data, we extracted HEPs. Estimation of the corticalHeart-evoked potentialsources of the taVNS-dependent HEP responses observed at the scalp were computed using theElectroencephalographyBoundary Element Method and weighted Minimum Norm Estimation. Statistics were calculated usingSource-localizationcluster-based permutation methods.Central autonomic networkResults: taVNS altered HEP amplitudes at frontocentral and centroparietal electrode sites at various latencies. The taVNS-dependent HEP effect was localized to the insula, operculum, somatosensory cortex,and orbital and ventromedial prefrontal regions.Conclusion: The results support the hypothesis that taVNS can access the insula as well as functionallyand anatomically connected brain regions. HEPs may serve as an objective, non-invasive outcomeparameter for the cortical effects of taVNS.© 2021 Published by Els
