Abstract
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.
Highlights
Transcutaneous auricular vagus nerve stimulation is a non-invasive electrical brain stimulation method that has been introduced as an alternative to direct or invasive vagus nerve stimulation[1]
During the rampup period, normalized pupil size decreased by 3.7 percent points per minute (χ2 = 45.6, p < 0.001, Fig. 1A), but was neither different between sham and Transcutaneous auricular vagus nerve stimulation (taVNS) (χ2 = 0.7, p = 0.397, Fig. 1A), nor did stimulation interact with time (χ2 = 0, p = 0.892, Fig. 1A)
We studied the effect of taVNS on tonic pupil size and event-related pupil dilation (ERPD)
Summary
Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive electrical brain stimulation method that has been introduced as an alternative to direct or invasive vagus nerve stimulation (iVNS)[1]. Mean overall pupil size during the baseline period was 2.9 mm (SD 1.3) and was not significantly different between sham and taVNS sessions (t32 = 0.92, p = 0.364, Fig. 1A).
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