Effects of non-invasive vagus nerve stimulation on pupil dilation are dependent on sensory matching.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising tool to modulate motivation and affect, with prior studies showing greater pupil dilation compared to sham. However, sensory differences between conditions may confound results. In a randomized crossover study with 94 participants, we applied right-sided pulsed taVNS (1 s, 20 Hz, and 400 μs) and calibrated stimulation amplitude to match subjective sensation. Contrary to expectations, taVNS did not significantly increase pupil dilation versus sham. However, when participants perceived sham as less intense, taVNS effects were stronger. Differences in perceived sensation between taVNS and sham were mainly linked to sham-induced pupil dilation. Our findings suggest that right-sided pulsed taVNS only leads to greater pupil dilation when a sensory mismatch occurs, underscoring the difficulty of creating an effective sham.