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bioRxiv · 10.1101/2025.06.13.659318

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

Vezzani, C.·Breakspear, R.-M.·Thurn, L.·Ettinger, U.·Kuehnel, A.·Kroemer, N. B.
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Abstract

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-invasive method to modulate motivation, cognition, and affect. According to a recent meta-analysis, pulsed taVNS induces larger pupil dilation (vs. sham), but sensory aspects of the stimulation may contribute to these differences. Moreover, included studies were often small and stimulation was only applied to the left ear, so that questions about the robustness and generalization remain. Here, we investigated the effects of pulsed taVNS (1s, 20Hz, 400{micro}s pulse width) at the right ear on phasic pupil dilation using a randomized crossover design in 94 participants (47 women). We initially calibrated the stimulation amplitude to match the perceived sensation across conditions and tracked sensation over time. Contrary to our hypothesis, taVNS did not elicit greater pupil dilation versus sham (b = -0.42, 95% CI [-1.30; 0.46], p = .35). However, taVNS effects were larger if sham was perceived as less intense despite the initial matching (b = 3.39, 95% CI [0.62; 6.17], p = .017). Differences in intensity ratings were mainly associated with sham-induced pupil dilation (r = -.25, 95% CI [-.43; -.05], p = .013). To summarize, our results recapitulate the findings of other studies using fixed amplitudes by showing that right-sided pulsed taVNS only induced larger pupil dilation against sham if differences in sensation arose. These findings highlight the challenge of establishing a suitable sham condition since both taVNS and sham affect sensory nerves, potentially leading to confounding effects.

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Vezzani, C., Breakspear, R.-M., Thurn, L., Ettinger, U., Kuehnel, A., Kroemer, N. B.. 2025-06-15. Effects of non-invasive vagus nerve stimulation on pupil dilation are dependent on sensory matching. https://doi.org/10.1101/2025.06.13.659318

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