In vivo evaluation of noninvasive temporal interference stimulation for tibial nerve-mediated bladder reflex modulation in rats

Transcutaneous tibial nerve stimulation (TTNS) is an established noninvasive neuromodulation approach for modulating bladder reflexes, although neural recruitment may vary with electrode configuration and tissue electrical properties. Temporal interference stimulation (TIS) is an emerging neuromodulation approach in which interacting kilohertz-frequency currents produce low-frequency amplitude modulation and may provide an alternative strategy for peripheral nerve stimulation. We investigated bladder reflex changes following noninvasive TIS applied over the intended tibial nerve region and explored its intensity-response pattern relative to conventional TTNS. In the primary experiment, rats were randomized to TIS or TTNS, and each rat was tested at five motor threshold (MT)-normalized intensity levels in a repeated-measures protocol. Cystometry assessed first voiding time (VT), intercontraction interval (ICI), and bladder pressure before and after each stimulation block. TIS showed the largest mean changes at 100% MT, with prolonged VT and ICI and reduced bladder pressure relative to baseline. Exploratory between-modality comparisons suggested different MT-normalized intensity-response patterns, with the largest VT and ICI differences at 100% MT; differences at other matched intensities were not significant. No significant between-modality bladder-pressure differences were detected. These findings provide a preliminary characterization of peripheral TIS intensity-response patterns for bladder reflex modulation and support further evaluation in disease-relevant models.