Cell-Specific Effects of Temporal Interference Stimulation on Cortical Function

Abstract Temporal interference (TI) stimulation is gaining tremendous interest as a non-invasive neurostimulation breakthrough. The observation is striking: pure sinusoid (generated in shallow brain regions) appears to cause no stimulation, whereas modulated sinusoid (generated in deeper brain regions) does. To understand its effects and mechanisms, we examine responses of different cell-types, excitatory pyramidal (Pyr) and inhibitory parvalbumin (PV) expressing neurons, to pure and modulated sinusoids, in intact network as well as in isolation. In intact network, we present data showing that PV neurons are much less likely than Pyr neurons to exhibit TI stimulation. Remarkably, in isolation, our data shows that almost all Pyr neurons stop exhibiting TI stimulation. We conclude that TI stimulation is largely a network phenomenon. Indeed, PV neurons have a substantially higher firing rate with pure 038 sinusoid (shallow brain) than with modulated sinusoid (deep brain), suggesting that in shallow regions, inhibitory PV neurons actively reduce firing of excitatory Pyr neurons. Additionally, we use computational models to study the (rare) neurons that do exhibit TI stimulation in isolation and observe that this can be explained by an integral-control based high-frequency current balance in the neural ion currents.