Cerebellum-Targeted Transcranial Focused Ultrasound Stimulation Modulates Hippocampus Neural Activities

Low-intensity transcranial focused ultrasound stimulation (tFUS) has recently emerged as a promising neuromodulation technique due to its non-invasive nature, ability to penetrate deeply, and high spatial resolution. On the other hand, the cerebellum has attracted new interest as a target for neuromodulation. In this study, we investigated how cerebellum-targeted tFUS could modulate hippocampal neural activity. We found that tFUS at pulse repetition frequency (PRF) as high as 10kHz can effectively activate the cerebellum in vivo. Furthermore, PRF at 10kHz, rather than 1kHz, favored remote inhibition of hippocampus neurons. We found that the neuromodulation at hippocampus was mainly mediated by cerebellum cortex than deep cerebellar nucleus. Furthermore, by cFos expression mapping and phase-amplitude coupling analysis, we showed that the hippocampal response at different PRFs resulted from altered neurodynamic interaction rather than overall activation of engaged brain regions. Our results reveal new potential for cerebellum as a neuromodulation target for hippocampus-related functions.