Modulated high-frequency stimulation enables precisely timed, selective nerve block

Current peripheral nerve stimulation (PNS) therapies are often constrained by the anatomical and functional complexity of nerves, resulting in limited efficacy and unwanted side effects. This study introduces a novel approach that enhances both spatial and functional selectivity in PNS by precisely controlling parameters of high-frequency sinusoidal stimulation delivered to one set of contacts and trapezoidal blocking pulses delivered to another set of contacts. Using an earthworm model, we demonstrate directional blocking of action potentials and precise temporal control over their propagation. By systematically varying stimulation waveform type, blocking pulse amplitude, and relative timing between the stimulation and blocking, we identified parameters that permit selective inhibition or activation of specific nerve fibers. Our findings show that slow and fast fibers can be independently targeted, and that action potential (AP) propagation can be modulated or blocked without interfering with initiation at the stimulation site. The study further proposes integrating independent anodal blocking with intermittent interferential current stimulation (i²CS), which could enable spatio-temporal control of nerve activity. This framework holds promise for advancing selective neuromodulation strategies in complex mammalian nerves, suggesting that precise control of stimulation and blocking via electrode configuration and waveform modulation can significantly improve the specificity and effectiveness of neuromodulation interventions.