Pulse Repetition Frequency Tuned Low-Intensity Focused Ultrasound Neuromodulation for Tibial Nerve Targeted Bladder Function Modulation
Young-Soo Lim, Hyunhee Kim, Chulhong Kim, Sung-Min Park
IEEE Transactions on Biomedical Engineering 2026 · 10.1109/tbme.2026.3700985
Abstract
Objective This study aims to investigate whether the neuromodulatory efficacy of low-intensity focused ultrasound (LIFU) for peripheral nerve stimulation (PNS) can be systematically tuned by the temporal stimulation parameter, pulse repetition frequency (PRF). Methods LIFU-mediated tibial nerve stimulation (LIFU-TNS) was applied with multiple PRF conditions to evaluate PRF-dependent neuromodulatory effects, with micturition inhibition as the primary outcome. Intra-bladder pressure (IBP) was continuously monitored to evaluate changes in micturition intervals. Neural involvement was confirmed using (1) a lidocaine-induced sciatic nerve (tibial branch) block, and the stimulation paradigm was additionally evaluated in (2) an acetic acid-induced overactive bladder model and (3) freely moving, unconstrained animals to assess robustness across physiological and behavioral conditions. Results A distinct PRF-dependent neuromodulation was observed, where 100 Hz stimulation elicited the most potent inhibition of micturition, whereas 10 Hz and 1 kHz showed comparatively less effective results. Quantitative analysis of normalized micturition interval (post-stimulation / pre stimulation baseline) confirmed this trend. (10 Hz: 0.98±0.16; 100 Hz: 1.72±0.81; 1 kHz: 0.95±0.35). Importantly, consistent inhibition was replicated across the nerve-block, overactive bladder, and freely moving models, indicating robustness of the effect under diverse physiological and behavioral conditions. Conclusion The clear PRF-dependent modulation observed in LIFU-TNS establishes PRF as a feasible and tunable control parameter and highlights its potential for guiding precise neuromodulation. Significance Unlike conventional intensity dependent strategies, this study demonstrates that PRF is essential for effective ultrasound neuromodulation in overactive bladder. These findings establish a systematic parameter-based framework for developing robust peripheral nerve interfaces.
Abstract via europepmc.
Exposures
Exposure 1: LIFU-TNS at PRF 10 Hz, 100 Hz, 1 kHz
Target: tibial nerve — “tibial nerve”
Device: Olympus / Panametrics · Olympus, USA · V301 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 10, 100, 1,000swept | ✓✓✓⚑ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 1,800 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Stimulation was applied continuously for 30 minutes, followed by a 1 hour resting period; PRF conditions (10 Hz, 100 Hz, 1 kHz) were applied as sequential trials in each subject in a designed order (Table S1).
Flags from extraction
n_subjects— 6 rats in the PRF experiment; numbers in the nerve-block, OAB and freely moving experiments are in the Supplement and not stated in the main textexposures[0].fundamental_frequency_khz— Frequency of the V301 transducer is not stated in the main textexposures[0].free_field— Peak pressure and MI are only in Fig. S2 (supplement); no values in the main textexposures[0].timing.sonication_duration_s— 30 minutes of stimulation per trial; pulse duration and duty cycle not stated in the main text, and the 30 min may include off-periods not describedexposures[0].timing.pulse_repetition_frequency_hz— 1 kHz PRF recorded as 1000 Hz; the abstract also lists 1 kHz