Prospects for transcranial temporal interference stimulation in humans: a computational study

Transcranial alternating current stimulation (tACS) is a noninvasive method used to modulate activity of superficial brain regions. Deeper and more steerable stimulation could potentially be achieved using transcranial temporal interference stimulation (tTIS): two high-frequency alternating fields interact to produce a wave with an envelope frequency in the range thought to modulate neural activity. Promising initial results have been reported for experiments with mice. In this study we aim to better understand the electric fields produced with tTIS and examine its prospects in humans through simulations with murine and human head models. A murine head finite element model was used to simulate previously published experiments of tTIS in mice. With a total current of 0.776 mA, tTIS electric field strengths up to 383 V/m were reached in the modeled mouse brain, suggesting that suprathreshold stimulation is possible in mice. Using a detailed anisotropic human head model, tTIS was simulated with systematically varied electrode configurations and input currents to investigate where interference fields are largest and why, the spatial extent of those fields, and how both are influenced by electrode placement and current strengths. An exhaustive search with 88 electrode locations covering the entire head (146M total current patterns) was employed to optimize tTIS fields. In all analyses, we investigated maximal effects and effects along the direction of the neurons. We found that it was possible to steer the peak tTIS field by manipulating the relative strength of the two input fields. Deep brain areas received field strengths similar to conventional tACS, but with less stimulation in superficial areas. Maximum field strengths were much lower than in the murine model, too low to expect direct stimulation effects. While field strengths were slightly higher with tACS, our results suggest that tTIS produces more focal fields and allows for better steerability. Finally, we present optimal four-electrode current patterns to maximize tTIS in regions of the pallidum (0.37 V/m), hippocampus (0.25 V/m) and motor cortex (0.57 V/m). We conclude that tTIS has potential as a more controlled version of tACS.