Pulse Repetition Frequency Tuned Low-Intensity Focused Ultrasound Neuromodulation for Tibial Nerve Targeted Bladder...

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).

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.

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.

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.

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.