Temporal interference stimulation for deep brain neuromodulation in humans

For decades, focal non-invasive neuromodulation of deep brain regions has not been possible because of the steep depth-focality trade-off of conventional non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) or classical transcranial electric stimulation (tES). Deep brain stimulation has therefore largely relied on invasive approaches in clinical populations, requiring surgery. Transcranial Temporal Interference Stimulation (tTIS) has recently emerged as a promising method to overcome this challenge and allows for the first time focal non-invasive electrical deep brain stimulation. The method, which was first validated through computational modeling and rodent work, has now been successfully translated to humans to target deep brain regions such as the hippocampus or striatum. In this Perspective, we present current evidence for tTIS-based neuromodulation, underlying mechanisms and discuss future developments of this promising technology. More specifically, we highlight key opportunities and challenges for fundamental neuroscience as well as for the design of new interventions in neuropsychiatric disorders. We also discuss the status of understanding and challenges regarding the basic mechanisms of action of tTIS and possible lines of technological innovation to optimize stimulation, in particular in terms of intensity and focality. Overall, we suggest that following the first proof-of-concepts, an important multidisciplinary research effort is now required to further validate the use of tTIS in multiple applications, understand its underlying principles and optimize the technology in the view of a wider scientific and clinical deployment.