Transcutaneous auricular vagus nerve stimulation modifies cortical excitability in middle-aged and older adults

There is a growing interest in the clinical application of transcutaneous auricular vagus nerve stimulation (taVNS). However, its effect on cortical excitability, and whether this is modulated by stimulation duration, remains unclear. We evaluated whether taVNS can modify excitability in the primary motor cortex (M1) in middle-aged and older adults and whether the stimulation duration moderates this effect. In addition, we evaluated the blinding efficacy of a commonly reported sham method. In a double-blinded randomized cross-over sham-controlled study, 23 healthy adults (mean age 59.91 ± 6.87 years) received three conditions: active taVNS for 30 and 60 min and sham for 30 min. Single and paired-pulse transcranial magnetic stimulation was delivered over the right M1 to evaluate motor-evoked potentials. Adverse events, heart rate and blood pressure measures were evaluated. Participant blinding effectiveness was assessed via guesses about group allocation. There was an increase in short-interval intracortical inhibition (F = 7.006, p = .002) and a decrease in short-interval intracortical facilitation (F = 4.602, p = .014) after 60 min of taVNS, but not 30 min, compared to sham. taVNS was tolerable and safe. Heart rate and blood pressure were not modified by taVNS (p > .05). Overall, 96% of participants detected active stimulation and 22% detected sham stimulation. taVNS modifies cortical excitability in M1 and its effect depends on stimulation duration in middle-aged and older adults. taVNS increased GABA_Aergic inhibition and decreased glutamatergic activity. Sham taVNS protocol is credible but there is an imbalance in beliefs about group allocation.