Transcutaneous auricular vagus nerve stimulation (taVNS) bears therapeutic potential for a wide range
of medical conditions. However, previous studies have found substantial interindividual variability
in responsiveness to taVNS, and no reliable predictive biomarker for stimulation success has been
developed so far. In this study, we investigate pupil size and event-related pupil response as candidate
biomarkers. Both measures have a direct physiological link to the activity of the locus coeruleus (LC),
a brainstem structure and the main source of norepinephrine in the brain. LC activation is considered
one of the key mechanisms of action of taVNS, therefore, we expected a clear increase of the
pupillary measures under taVNS compared to sham (placebo) stimulation, such that it could serve as a
prospective predictor for individual clinical and physiological taVNS effects in future studies. We studied
resting pupil size and pupillary responses to target stimuli in an auditory oddball task in 33 healthy
young volunteers. We observed stronger pupil responses to target than to standard stimuli. However,
and contrary to our hypothesis, neither pupil size nor the event-related pupil response nor behavioral
performance were modulated by taVNS. We discuss potential explanations for this negative finding and
its implications for future clinical investigation and development of taVNS.DFG-Publikationsfonds 201
