Characterization of Electrodes to Record Neural Signals in the Periphery.

Appropriately designed electrodes to make in vivo recordings of neural activity have been essential to understanding the nervous system. Recording electrode design has been extensively explored for use in measurement of naturally occurring neural activity in the brain. Recently, recordings of evoked compound action potentials (ECAPs) in the periphery have garnered interest due to their relevance in neuromodulation therapies for determining target engagement and enabling closed-loop operation. Here, we compare three types of recording electrodes - microelectrodes, cuff electrodes, and intrafascicular electrodes - and their ability to make in vivo recordings of electrically ECAPs, naturally occurring neural activity, and sensory evoked neural activity in the peripheral nerves of a human-relevant large animal model. The great auricular nerve, innervating the auricle, and cervical vagus nerve of domestic pigs were instrumented with the three recording electrodes. Naturally occurring neural activity, sensory evoked neural activity induced by gentle brushing of the auricle, and electrically ECAPs initiated by non-invasive and invasive stimulation electrodes were recorded. The study was pre-registered (https://osf.io/y9k6j). We showed that the recording cuff had superior performance in measuring invasive electrically ECAPs (p < 0.05) while the tungsten microelectrode, routinely used for microneurography in humans, had superior performance in measuring naturally occurring action potentials (p < 0.05). The microelectrode was still able to record electrically ECAPs. Further, we show how choice of reference electrode position may be optimized per application. Microneurography recordings paired with the deployment of a non-invasive neuromodulation therapy can be used to functionally map sensory innervation areas in patients, allowing individualized placement of stimulation electrodes to achieve on-target neural fiber activation. These findings provide a basis to select recording electrode type and configuration for measurement of neural signals in the development and deployment of neuromodulation therapies.