Cognitive and autonomic physiological responses to daily transcutaneous auricular vagus nerve stimulation in healthy adults

IntroductionThe vagus nerve regulates autonomic processes central to cognition. Transcutaneous auricular vagus nerve stimulation (taVNS) can acutely modulate executive function in healthy adults, but the effects of repeated dosing, roles of executive subdomains, and importance of sex as a biological variable require clarification. MethodIn a randomized, single-blind, sham-controlled, parallel group study, 12 healthy adults (six women) received 10 consecutive days of left monoaural taVNS (VNS) or sham (CON), with a two-week follow-up rechallenge. Stimulation (100Hz; 200{micro}s pulse width) was delivered continuously (online) at rest and during the Eriksen Flanker (inhibition), Wisconsin Card Sorting (shifting), and Sternberg (working memory) tasks. Resting autonomic measures included pupil diameter, skin conductance (SCL), mean R-R interval (mRR), respiration, and blood pressure. Primary outcomes were analyzed with linear mixed models and [S]idak-corrected contrasts. ResultsTen days of taVNS produced immediate and cumulative changes in multiple executive function subdomains that remained evident at rechallenge, with the strongest effects on accuracy. Across tasks, benefits were most pronounced in women; men displayed initial performance costs, but with greater longitudinal improvements. Cognitive effects were most evident on higher-difficulty trials. Autonomically, taVNS increased SCL during and after stimulation, amplified stimulus- and task-evoked pupil responses, and transiently lengthened mRR. Stimulation was well tolerated and blinding was acceptable. ConclusionsResolution of taVNS effects to higher-difficulty trials supports adaptive-gain modulation within executive function networks. The combination of larger evoked pupil/SCR, transient mRR lengthening, and increased SCL indicates that taVNS increased autonomic flexibility and arousal. Our findings identify biological sex and stimulation intensity as potentially important considerations for taVNS efficacy and provide longitudinal estimates to guide dosing, biomarker selection, and trial design. Collectively, the results support continued development of taVNS as a safe tool for the modulation of executive function and autonomic activity in healthy adults.