Controlling focality and intensity of non-invasive deep brain stimulation using multipolar temporal interference in non-human primates and rodents

Abstract

Abstract Temporal interference (TI) stimulation is a unique method of non-invasive deep brain stimulation (DBS) using transcutaneous electrodes which allows the targeting and stimulation of deeper brain structures while avoiding unwanted stimulation of shallower cortical structures. The DBS property of TI has been previously demonstrated, however, the problem of decoupling stimulation focality from stimulation intensity has not been addressed. In this paper, we directly solve the problem with a novel multipolar TI (mTI) stimulation method, which allows independent control over both the size of the stimulated region and the stimulation intensity. The mTI method uses multiple carrier frequencies to create multiple overlapping envelopes. The study presents a theoretical explanation of the concept of mTI along with experimental data gathered from Rhesus macaques and mice, permitting comparison of our technique’s focality to that of the classic temporal interference stimulation technique. We show that we are able to improve the focality at depth in the brain of anesthetized mice and monkeys, and - using the new focality in awake monkeys - to evoke targeted activity, at depths never reached using non-invasive transcutaneous electrodes, namely in the superior colliculus. Finally, our results are guided and interpreted using electrodynamic simulations of mTI stimulation in a detailed monkey model.