Pulsed taVNS-Elicited Pupil Dilation: Effects of Intermixed Stimulation, Sham Location, and Respiratory Phase

Transcutaneous auricular vagus nerve stimulation (taVNS) may offer a powerful, noninvasive way to stimulate activity of brainstem arousal systems, including the locus coeruleus-norepinephrine (LC-NE) system. Pulsed taVNS is known to elicit pupil dilation, a marker of LC activity. However, studies reporting taVNS effects on pupil dilation have delivered taVNS and sham stimulation in separate blocks of trials or in separate sessions, hindering the integration of taVNS into rapid, event-related task designs of cognitive neuroscientists. In two experiments, we examined the effectiveness of pulsed taVNS in eliciting pupil dilation when active and sham stimulation were intermixed within the same blocks of trials and whether these effects depend on sham location and respiratory phase. In Experiment 1 (N = 40), intermixed taVNS and (earlobe) sham pulses of 3.4 s produced inconclusive evidence for increased taVNS-evoked pupil dilation. In contrast, in Experiment 2 (N = 60), taVNS pulses of 1.0 s had a strong effect on pupil dilation, but only in a group of participants that received sham stimulation at the earlobe; this effect was abolished in a group that received sham stimulation at the upper scapha, a non-vagal control area with a similar density of sympathetic nerve fibers as the cymba concha. Furthermore, taVNS-evoked pupil dilation was not enhanced when stimulation was delivered during exhalation, as would be expected if pupil effects were mediated by the vagus nerve-nucleus tractus solitarius-LC pathway. Together, these findings show that the effect of pulsed taVNS on pupil dilation can be preserved when taVNS and (earlobe) sham are delivered in the same blocks of trials. However, the null finding with the scapha as a sham location and the absence of an enhanced taVNS effect during exhalation call into question the assumption that taVNS-induced pupil dilation is mediated by activation of the vagal afferent pathway.