Continuous Transcutaneous Auricular Vagus Nerve Stimulation Increases Long-Latency Neural Processing in Multiple Sensory Modalities.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive 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 continuous taVNS enhances standard NA markers along with neural processing in three sensory modalities (auditory, respiratory, and somatosensory). In a 2-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-/poststimulation to assess alpha-band (8-13 Hz) 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 taVNS research.