Abstract
Transcranial electrical stimulation (tES) has emerged as a promising tool for neuromodulation, but its application is often limited by the discomfort associated with higher stimulation intensities. Newer variants like transcranial temporal interference stimulation (tTIS) utilize high-frequency alternating currents (≥ 500 Hz) to penetrate deeper brain regions while mitigating perceptual discomfort. This study sought to examine sensation and pain thresholds across various stimulation frequencies of alternating currents, aiming to explore the boundaries of comfortable intensities. Additionally, we sought to evaluate the efficacy of an anesthetizing topical cream in increasing participant comfort and potentially extending the range of tolerable stimulation levels. We recruited 37 participants and applied alternating current stimulation to the head at various frequencies (10 Hz, 20 Hz, 500 Hz, 1000 Hz, and 2000 Hz) to determine intensity-dependent perception and pain thresholds. Additionally, thresholds were determined under the influence of a topical anesthetic. Our findings confirm that as stimulation frequency increases, perceptibility decreases, with higher frequencies allowing a manyfold increase in stimulation intensity before becoming perceptible or causing pain. Additionally, the anesthetizing cream was efficacious in further reducing perceptibility and pain sensations across all frequencies. This study lays the groundwork for future research by establishing comfortable limits for stimulation intensities, particularly in the context of high-frequency stimulation. The reduced perceptibility of high-frequency stimulation, coupled with the effectiveness of anesthetizing creams, enables the administration of higher stimulation intensities for more potent neuromodulatory interventions without causing discomfort.