Cerebellar focused ultrasound stimulation modulates neural response at hippocampus and suppresses epileptiform activity.

INTRODUCTION

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.

MATERIALS AND

METHODS

In this study, the effects of cerebellum-targeted tFUS in modulating hippocampal neural activity is investigated. We used a fundamental frequency of 500 kHz with duty cycle of 50%, duration of 500 ms and interstimulus interval of 10sec. Specifically, we examined the neuromodulation effect of two different pulse repetition frequencies (PRF) (1 kHz vs. 10 kHz) of the tFUS based on electrophysiological recording, cFos expression and neural dynamic analysis. We also investigated the potential clinical application of this works in an acute seizure model of rat using 4-AP injection with PRF of 10 kHz.

RESULTS

It was found that tFUS at PRF as high as 10 kHz can effectively activate the cerebellum in vivo. Furthermore, PRF at 10 kHz, rather than 1 kHz, favors remote inhibition of hippocampus neurons. It is also shown that the neuromodulation at hippocampus is mainly mediated by cerebellum cortex than deep cerebellar nucleus. Furthermore, by cFos expression mapping and phase-amplitude coupling analysis, it is shown that the hippocampal response at different PRFs resulted from altered neurodynamic interaction rather than overall activation of engaged brain regions. We further demonstrated that the cerebellum-targeted tFUS could effectively suppress epileptiform activity in an acute seizure model of rats.

CONCLUSION

The results reveal new potential for cerebellum as a neuromodulation target for hippocampus-related functions. We have also shown that PRF is an important control parameter to the subsequent neural response.