Safety, tolerability and blinding efficiency of non-invasive deep transcranial temporal interference stimulation: first experience from more than 250 sessions

Abstract Objective . Selective neuromodulation of deep brain regions has for a long time only been possible through invasive approaches, because of the steep depth-focality trade-off of conventional non-invasive brain stimulation (NIBS) techniques. Approach . An approach that has recently emerged for deep NIBS in humans is transcranial Temporal Interference Stimulation (tTIS). However, a crucial aspect for its potential wide use is to ensure that it is tolerable, compatible with efficient blinding and safe. Main results . Here, we show the favorable tolerability and safety profiles and the robust blinding efficiency of deep tTIS targeting the striatum or hippocampus by leveraging a large dataset (119 participants, 257 sessions), including young and older adults and patients with traumatic brain injury. tTIS-evoked sensations were generally rated as ‘mild’, were equivalent in active and placebo tTIS conditions and did not enable participants to discern stimulation type. Significance . Overall, tTIS emerges as a promising tool for deep NIBS for robust double-blind, placebo-controlled designs.