No effect of continuous transcutaneous auricular vagus nerve stimulation on the P3, the P600, or physiological markers of norepinephrine activity in an oddball and sentence comprehension task

The ERP components P3 and P600 have been proposed to reflect phasic activity of the locus coeruleus norepinephrine (LC/NE) system in response to deviant and task-relevant stimuli across cognitive domains. Yet causal evidence for this link remains limited. Here, we used continuous transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method proposed to modulate LC/NE activity, to test whether these components are indeed sensitive to NE manipulation. Forty participants completed both an active visual oddball task and a sentence processing task including both syntactic and semantic violations, while receiving continuous taVNS at the cymba conchae in one session and sham stimulation at the earlobe in another session. We observed robust P3 and P600 effects. Crucially though, taVNS had no effect on P3 or P600 amplitude. The physiological NE markers salivary alpha amylase level and baseline pupil size were also unaffected by the stimulation, suggesting that the taVNS protocol and/or task may not have been sufficient to successfully engage the LC/NE system. Beyond the stimulation, however, exploratory analyses revealed correlations between the syntactic P600 and both the P3 and salivary alpha amylase levels, supporting the idea that the P600 might be related to both the P3 and NE. Overall, our findings do not allow for theoretical implications concerning a potential causal link between the two components and NE but highlight the need for more standardized taVNS protocols.