Cerebellar focused ultrasound stimulation modulates neural response at hippocampus and suppresses epileptiform activity
Yingjian Liu, King Yi Cho, Jacky Tin Shing Hung, Caiyi Zhuo, Wenxin Shi, Hei Ming Lai, Chung Tin
Brain Stimulation 2026 · 10.1016/j.brs.2026.103097
Abstract
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.
Abstract via europepmc.
Exposures
Exposure 1: Cerebellum-targeted tFUS, PRF 1 kHz vs 10 kHz (plus 10 kHz in 4-AP seizure model)
Target: cerebellum — “cerebellum”
Device: Olympus / Panametrics · Olympus, USA · V301-SU flat transducer with 2 mm collimator ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reported | ⚑ |
| Pulse repetition frequency (Hz) | 1,000, 10,000swept | ✓✓✓ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 0.5, 1swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | 210 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 1.53 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 100 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 0.35 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
FF 500 kHz, DC 50 %, PRF 1 or 10 kHz with burst duration adjusted to keep DC constant (burst duration not given in text); UD 500 ms, ISI 10 s; 20 min for cFos. Seizure model: PRF 10 kHz, DC 50 %, UD 1 s, ISI 5 s, 10 min.
Flags from extraction
exposures[0].free_field.pressure_kpa— Converted from 0.21 MPa; measured by hydrophone without cranium. The paper does not say which PRF these values correspond to.exposures[0].in_situ.pressure_kpa— Converted from 0.10 MPa; hydrophone measurement through a freshly excised rat cranium in water (not brain tissue).exposures[0].timing.sonication_duration_s— 500 ms in main experiments and 1 s in the seizure model; the 1 s value is quoted in methods 2.14 and 3.x, not under this quote.exposures[0].timing.pulse_duration_ms— Burst duration per pulse stated only in a figure and not in text.n_subjects— 13 rats in the PRF recording experiment; other experiments used 3 per group (GsMTx4), 5 per group (cFos slices, seizure), 1 per group (whole-brain cFos); overlap not stated.sham_type— Control rats received no tFUS; a separate artefact check aimed ultrasound at the upper part of the electrode array.conditions— Epilepsy refers to an acute 4-AP seizure model; the rest of the work is in non-epileptic rats.