Wang, Y.; Tushar, M. A. K.; Lucero, O.; Zimmern, P. E.; Li, Z.

Objective: Neurogenic lower urinary tract dysfunction (NLUTD) impairs bladder control and remains difficult to treat. We aim to define how electrical stimulation (ES) parameters of the external urethral sphincter (EUS) affect urinary leakage thresholds to guide neuromodulation strategies for NLUTD. Methods: We performed direct EUS stimulation in anesthetized rats using charge-balanced biphasic pulses while systematically varying current amplitude (0.5-3.0 mA), frequency (20-100 Hz), and pulse duration (0.5-3 ms). Urine leakage thresholds were mapped across the multidimensional parameter space. Results: Stimulation parameters exhibited strong nonlinear interdependence in determining leakage onset. At a fixed pulse duration, higher current amplitudes required lower stimulation frequencies to evoke leakage. Increasing pulse duration substantially reduced both current and frequency thresholds. Age and sex caused modest shifts in absolute thresholds but did not alter the fundamental parameter-response relationships. Conclusion: Pulse duration, current amplitude, and frequency jointly govern urinary leakage thresholds, with pulse duration serving as the dominant modulator of stimulation efficiency. Significance: This work establishes a quantitative framework for charge-efficient stimulation parameter selection, enabling the design of energy-aware, precision neuromodulation protocols and implantable systems for NLUTD rehabilitation.