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

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. 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. 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. Overall, tTIS emerges as a promising tool for deep NIBS for robust double-blind, placebo-controlled designs.