Selective activation of nerve fiber subpopulations with intrafascicular stimulation

Background: Peripheral nerve stimulation (PNS) is most effective when specific nerve fiber subpopulations are activated, while minimizing off-target activation, which may cause undesirable side effects. This selectivity depends primarily on electrode design and charge delivery. We hypothesized that selective PNS could be achieved through electrode placement and intrafascicular electric field steering using Longitudinal Intrafascicular Electrodes (LIFEs). Methods: LIFEs were implanted into the tibial fascicle of the sciatic nerve of 17 anesthetized adult rats. We tested whether electrodes positioned at different cross-sectional and longitudinal locations within the same fascicle, together with different electric field-steering approaches produced distinct activation patterns in the gastrocnemius lateralis muscle. Muscle responses were measured using high-density epimysial electromyography (HD-eEMG). Results: Electrodes placed at different locations within the same fascicle activated distinct muscle regions, demonstrating intrafascicular selectivity. Bipolar stimulation recruited nerve fibers differently than monopolar stimulation, showing that electric field steering can further shape the selective recruitment. In both configurations, increasing the stimulation amplitude produced a graded increase in muscle activation. Furthermore, our findings demonstrated that HD-eEMG is an effective tool for evaluating intrafascicular selectivity. Conclusion: These findings suggest that improving on-target selectivity may support next-generation bioelectronic therapies with better outcomes and fewer side effects, potentially enabling more precise, organ-specific neuromodulation. Using multiple intrafascicular electrodes may provide two complementary strategies for enhancing selectivity: strategic intrafascicular placement to access different fiber subpopulations and bipolar configurations to steer recruitment beyond what a single electrode can achieve.