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

## TL;DR

Non-invasive vagus nerve stimulation does not reliably increase pupil dilation unless there is a mismatch in perceived sensation between the real and sham conditions.

## Contribution

The study reveals that sensory matching between taVNS and sham conditions is critical for interpreting pupil dilation as a biomarker.

## Key findings

- taVNS did not significantly increase pupil dilation compared to sham when sensations were matched.
- Sham-induced pupil dilation was linked to differences in perceived sensation between taVNS and sham.
- Right-ear taVNS reduced left-right pupil correlation after stimulation.

## Abstract

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.

•taVNS does not increase pupil dilation vs. sham when sensation is matched•Differences in sensation for taVNS vs. sham are linked to sham-induced pupil dilation•Right-ear taVNS reduced left-right pupil correlation after stimulation•Sensory matching is critical for using pupil dilation as a taVNS biomarker

taVNS does not increase pupil dilation vs. sham when sensation is matched

Differences in sensation for taVNS vs. sham are linked to sham-induced pupil dilation

Right-ear taVNS reduced left-right pupil correlation after stimulation

Sensory matching is critical for using pupil dilation as a taVNS biomarker

Neurology; Eye observable entity; Affect; Procedure by device; Sensory neuroscience