# Vagus nerve stimulation alters task‐evoked pupillary responses in older but not younger adults: A single‐blind active sham‐controlled crossover trial

## TL;DR

Vagus nerve stimulation affects pupil responses in older adults but not younger adults, suggesting age-related differences in brain activity.

## Contribution

This study reveals age-specific effects of vagus nerve stimulation on locus coeruleus-related physiological responses.

## Key findings

- Older adults showed increased tonic pupil size and reduced oddball-evoked responses during VNS.
- Younger adults exhibited no consistent VNS effects on pupil responses.
- VNS effects were stronger with higher current in older adults.

## Abstract

The locus coeruleus (LC) undergoes age‐related changes and is involved in Alzheimer's disease pathogenesis. Vagus nerve stimulation (VNS) may modulate LC activity and could be used therapeutically, but age‐related differences in VNS responses remain unexplored.

We used a single‐blind, sham‐controlled, crossover design in 41 participants (21 younger, 20 older adults). Participants completed a visual oddball task with pupillometry during transcutaneous auricular VNS (verum: cymba concha; sham: earlobe) with ≈ 30 minutes of washout between conditions.

Older adults showed smaller baseline pupil diameter but larger normalized task‐evoked responses than younger adults a priori. VNS produced age‐specific effects: older adults demonstrated increased tonic pupil size throughout stimulation and reduced oddball‐evoked responses, with stronger effects with more current. Younger adults showed no consistent VNS effects.

VNS affects LC‐related physiological measures differently across age groups, with older adults showing more robust responses. These age‐specific effects may reflect different baseline LC activity states.

Transcutaneous vagus nerve stimulation (tVNS) can affect the locus coeruleus (LC).Pupil size and responses are a useful proxy for LC neuronal activity.We tested tVNS in a sham‐controlled single‐blind crossover trial.We found effects of tVNS on phasic pupil responses in older but not younger adults.tVNS responsiveness could reveal underlying differences in LC status.

Transcutaneous vagus nerve stimulation (tVNS) can affect the locus coeruleus (LC).

Pupil size and responses are a useful proxy for LC neuronal activity.

We tested tVNS in a sham‐controlled single‐blind crossover trial.

We found effects of tVNS on phasic pupil responses in older but not younger adults.

tVNS responsiveness could reveal underlying differences in LC status.