Enhancing Selectivity in Vagus Nerve Stimulation via Intermittent Interferential Current Steering

Introduction: Vagus nerve stimulation (VNS) is emerging as a promising therapeutic approach for a range of chronic disorders. However, its clinical potential is hindered by limited selective targeting of specific nerve fibers while avoiding off-target effects. We introduce a novel stimulation strategy using intermittent interferential current stimulation (i2CS) delivered through a multi-contact epineural cuff.

Methods: We validate the i2CS approach in an anesthetized swine model and computer simulations based on the anatomy from the experiment and biophysical models of VNS.

Results: In anesthetized swine, i2CS elicited distinct compound nerve potentials and organ-specific responses in the lungs and laryngeal muscles, which differed from those induced by equivalent, non-interferential sinusoidal stimulation. Post-mortem micro-CT imaging of a stimulated nerve revealed that these effects stem from differential activation of fibers within fascicles innervating specific end-organs. Computer simulations using anatomically and physiologically validated biophysical models of VNS confirmed that i2CS reduces activation at the interference focus.

Conclusion: Experimental and modeling results demonstrate that current steering, beat duration and pulse repetition frequency predictably determine the spatiotemporal activation of fibers, permitting tuneable and precise control of nerve and organ responses. Control of fiber activation by i2CS can be improved further by addition of spatially confined and precisely timed blocking pulses.