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

Abstract

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, affirming experimental results indicating 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 how these parameters influence the electric fields. An exhaustive search with 88 electrode locations covering the entire head (146M current patterns) was employed to optimize tTIS for target field strength and focality. In all analyses, we investigated maximal effects and effects along the predominant orientation of local neurons. Our results showed 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 in the human model were much lower than in the murine model, too low to expect direct stimulation effects. While field strengths from tACS were slightly higher, our results suggest that tTIS is capable of producing 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 (0.24 V/m) and motor cortex (0.57 V/m).

Temporal interference stimulation targets deep brain regions by modulating neural oscillations

“…In cortex, unmodulated electric field magnitudes can reach ~0.48 V/m per mA applied current, while in deep brain areas amplitude-modulation of electric fields can reach ~0.36 V/m per mA applied current. Therefore, while amplitude-modulated kHz stimulation can be directed to deep brain regions, on the cortex electric field magnitudes will also be high, consistent with prior models 3,4 .…”

“…While targeted deep brain structures are exposed to an amplitude-modulated kHz electric fields, superficial cortex is stimulated with higher magnitude unmodulated kHz electric fields. The effectiveness of temporal interference stimulation 2 thus depends on: 1) steerability of the amplitude-modulated electric fields to targeted deep brain regions 3,4 ; 2) the extent to which neuronal activity is more responsive to amplitude-modulated high-frequency electric fields compared to unmodulated electric field (selectivity); 3) the current intensity requirement at the scalp to produce sufficiently strong amplitude-modulated kHz fields deep in the brain (sensitivity).…”

Optimization of interferential stimulation of the human brain with electrode arrays

“…Each electrode can apply different current intensities for each frequency. This is significantly more flexible than recent optimization efforts for IFS that have been limited to pairs of electrodes of a single frequency each (Rampersad et al, 2019;Cao and Grover, 2019;Xiao et al, 2019). The approach can be readily implemented with existing multi-channel TES hardware by connecting the two current sources (of different frequency) to a single set of electrodes.…”

“…This generalizes the conventional IFS approach (Grossman et al, 2017) in that each frequency is now applied to potentially more than one electrode pair. It is also more flexible than recent efforts to target IFS with multiple pairs as they are limited to applying only one oscillating frequency at each pair (Rampersad et al, 2019;Cao and Grover, 2019). In contrast, here each electrode can apply the sum of two oscillating currents, and thus we can variably distributed the two frequencies over all electrodes in the array.…”

“…A series of approaches have been propose, but all are limited in some respect. Rampersad et al (2019) searches through a large number of montages with two pairs of electrodes, but does not systematically tackle the general problem of arrays. Cao and Grover (2019) suggests the use of arrays, but fails to take interference into account by optimizing each frequency separately.…”