High-frequency amplitude-modulated sinusoidal stimulation induces desynchronized yet controllable neural firing.

Regaining sensory feedback is pivotal for people living with limb amputation. Electrical stimulation of sensory fibers in peripheral nerves has been shown to restore focal percepts in the missing limb. However, conventional rectangular current pulses induce sensations often described as unnatural. This is likely due to the synchronous and periodic nature of activity evoked by these pulses. Here we introduce a fast-oscillating amplitude-modulated sinusoidal (FAMS) stimulation waveform that desynchronizes evoked neural activity. We used a computational model to show that sinusoidal waveforms evoke asynchronous and irregular firing and that firing patterns are frequency dependent. We designed the FAMS waveform to leverage both low- and high-frequency effects and found that membrane non-linearities enhance neuron-specific differences when exposed to FAMS. We implemented this waveform in a feline model of peripheral nerve stimulation and demonstrated that FAMS-evoked activity is more asynchronous than activity evoked by rectangular pulses, while being easily controllable with simple stimulation parameters. These results represent an important step towards biomimetic stimulation strategies useful for clinical applications to restore sensory feedback.