High pressure transcranial focused ultrasound stimulation induces parameter-dependent cell-type specific effects.

Transcranial focused ultrasound (tFUS) is a promising technique that has been shown to have high spatial precision, deep brain penetration, and cell-type specificity. Intracranial electrophysiological recordings can measure neural responses to tFUS with high spatial and temporal resolution, but conventional silicon-based multi-electrode arrays cause vibration artifacts induced by increased tFUS pressure. In this study, using an ultraflexible nanoelectric thread electrode, we demonstrate the cell-type selective effects of tFUS under high acoustic pressure with a broad range of ultrasound parameters. We observe that their flexibility mitigates vibrations, eliminating artifacts even at high pressure levels. We observed a positive nonlinear relationship between pressure levels and both time-locked and delayed spiking responses in multiple cell types. We show that higher pressure levels produce distinct response curves across independently varied ultrasound pulse repetition frequency and duty cycle, suggesting the need for further investigation of pressure effects.