Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive technique stimulating vagal afferent fibers, showing promise in treating neurological and mental disorders. taVNS is believed to activate the locus coeruleus (LC), promoting noradrenergic activation (NA), which enhances arousal and attention. However, evidence for the LC-NA hypothesis is mixed, and investigations in different sensory modalities are lacking. This study investigated whether taVNS enhances standard NA markers along with neural processing in three sensory modalities (auditory, respiratory, and somatosensory). In a two-day Sham-controlled crossover protocol, 45 healthy adults received taVNS at the cymba concha and Sham stimulation at the earlobe. During stimulation, participants experienced paired auditory clicks, inspiratory occlusions and electrocutaneous stimuli, while EEG was acquired. Salivary alpha-amylase (sAA) and subjective experienced arousal were measured at pre-/end-stimulation. Resting-state EEG was measured pre-/post-stimulation to assess alpha-band (8-13Hz) oscillation power, and participants rated the intensity and unpleasantness of all stimuli. Auditory-, respiratory-related-, and somatosensory evoked potentials were measured, specifically P50, N1, and P2 components, as well as the P50/N1 amplitude difference of the second and the first stimulus in the pair (neural gating; S2-S1). Although no effects in P50 or N1 amplitudes were observed, P2 amplitudes in auditory and somatosensory blocks increased during taVNS. Self-reported arousal increased in the taVNS condition, with no effects on neural gating, sAA concentration, or resting-state alpha power. taVNS had no effect on self-reported intensity/unpleasantness of stimuli. These results highlight certain limitations posed by combining taVNS and EEG, and underline the need for further mechanistic and clinical taVNS research.

javascript:void(0) Recently, we found that continuous transcutaneous auricular vagus nerve stimulation (taVNS) facilitates the encoding and later recollection of emotionally relevant information, as indicated by enhanced late positive potential (LPP), memory performance, and late ERP Old/New effect. Here, we aimed to conceptually replicate and extend these findings by investigating the effects of different time-dependent taVNS stimulation protocols. In Study 1, an identical paradigm to our previous study was employed with interval stimulation (30-sec on/off). Participants viewed unpleasant and neutral scenes on two consecutive days while receiving taVNS or sham stimulation and completed a recognition test one week later. In line with our previous results, unpleasant images encoded under taVNS, compared to sham stimulation, elicited larger LPP amplitudes and Old/New effects. However, no effects of taVNS on memory performance were found, suggesting that interval stimulation may lower the effects of taVNS on memory. In Study 2, we followed up on these findings by synchronizing the stimulation cycle with image presentation to determine the taVNS effects for images encoded during the on and off cycles. We could replicate the enhancing effects of taVNS on brain potentials (LPP and late Old/New effect) and found that taVNS improved recollection-based memory performance for both unpleasant and neutral images, independently of the stimulation cycle. Overall, our results suggest that taVNS increases electrophysiological correlates of emotional encoding and retrieval in a time-independent manner, substantiating the vagus nerve’s role in emotional processing and memory formation and opening new venues for improving mnemonic processes in both clinical and non-clinical populations.