LTP-like noninvasive striatal brain stimulation enhances striatal activity and motor skill learning in humans

The stimulation of deep brain structures has thus far been possible only with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here, we show for the first time successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, fMRI studies and behavioral evaluations. Theta-burst patterned, LTP-like striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor learning capacity, especially in healthy older participants, who have lower natural learning capacity than younger subjects. These findings suggest exciting methods for noninvasively targeting deep brain structures in humans, thus enhancing our understanding of their functional roles. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders, in which deep brain structures play key pathophysiological roles. ### Competing Interest Statement N.G. and E.N. are co-founders of TI Solutions AG, a company committed to producing hardware and software solutions to support TI research.