Neuronal responses to focused ultrasound are gated by pre-stimulation brain rhythms.

Owing to its high spatial resolution and penetration depth, transcranial focused ultrasound stimulation (tFUS) is one of the most promising approaches to non-invasive neuromodulation. Identifying the impact of endogenous neural activity on neuromodulation outcome is critical to harnessing the potential of tFUS. Here we sought to identify the relationship between pre-stimulation neural activity and the neuronal response to tFUS. We applied 3 min of continuous-wave tFUS to the hippocampal region of the rat while recording local field potentials (LFP) and multi-unit activity (MUA) from the target. We also tested the application of tFUS but with an air gap separating the transducer and the skull, as well as active stimulation of the contralateral olfactory bulb. We observed a modest but significant increase in firing rate during hippocampal tFUS, but not during stimulation of the olfactory bulb or when an air gap was present. Importantly, the observed firing rate increase was significantly modulated by the power of baseline oscillations in the LFP, with low levels of delta (1-3 Hz) and high levels of theta (4-10 Hz) and gamma (30-250 Hz) power producing significantly larger firing rate increases. Firing rate increases were also amplified by a factor of 7× when stimulation was applied during periods of frequent sharp-wave ripple (SWR) activity. Our findings suggest that baseline brain rhythms may effectively "gate" the response to tFUS.