Novelty-dependent enhancement of sustained attention and electrophysiological signatures via transcutaneous auricular vagus nerve stimulation

Sustained attention relies on Locus coeruleus - Noradrenaline (LC-NA) activity with tonic activity regulating arousal and phasic responses facilitating stimulus processing. In animals, phasic LC activity also depends on novelty of situations, yet human evidence is missing. Transcutaneous auricular vagus nerve stimulation (taVNS) was used to noninvasively modulate activity in the LC-NA system in forty-four healthy participants (36 female) while they completed a gradual-onset Go-Nogo task on two days ≥ 24 hours apart while EEG was recorded. 500 ms taVNS was applied with each stimulus onset either in the first, novel or second, familiar session while sham stimulation was applied in the remaining session. When delivered during the first, novel session, taVNS accelerated reaction times, reduced response variability, and attenuated the typical block-wise decline in subjective focus. Concurrently, fronto-central P1-N1 and parietal N1-P2 amplitudes were enhanced, and larger P1-N1 amplitudes predicted faster responses, linking early cortical gain to behavioral performance. Improvements persisted into the next-day sham session, whereas taVNS applied only during the familiar second session was ineffective. The results support a mechanistic account in which taVNS selectively enhances novelty-dependent phasic LC activity, underscoring context as critical for taVNS effects.