Label-free functional imaging of vagus nerve stimulation-evoked potentials at the cortical surface

Vagus nerve stimulation (VNS) is an FDA-approved stimulation therapy to treat patients with refractory epilepsy. In this work, we use a coherent holographic imaging system to characterize vagus nerve-evoked potentials (VEPs) in the cortex in response to VNS stimulation paradigms without electrode placement or any genetic, structural, or functional labels. We analyze stimulation amplitude up to saturation, pulse width up to 800 μs, and frequency from 10 Hz to 30 Hz, finding that stimulation amplitude strongly modulates VEPs response magnitude (effect size 0.401), while pulse width has a moderate modulatory effect (effect size 0.127) and frequency has almost no modulatory effect (effect size 0.009) on the evoked potential magnitude. We find mild interactions between pulse width and frequency. This non-contact label-free functional imaging technique may serve as a non-invasive rapid-feedback tool to characterize VEPs and may increase the efficacy of VNS in patients with refractory epilepsy.