(44) Intraneural Slanted Multi-electrode Arrays Enable Single Fiber Recording, Spatially Selective Stimulation in Swine Vagus Nerve

Introduction: The vagus nerve plays a crucial role in regulating physiological and immune homeostasis, mediating vital communication between the central nervous system and peripheral organs. Vagus nerve stimulation (VNS) using cuff electrodes has emerged as a promising therapeutic approach for treating various diseases. Recording activity of multiple fibers from the VN would facilitate mechanistic studies in large animals and humans and potentially support closed-loop VNS approaches, but it is not feasible with cuffs. In addition, cuff electrodes for VNS lack stimulation selectivity and are associated with side effects which limit their clinical efficacy. Intraneural multi-electrode arrays (MEAs) may simultaneously address both these limitations but their recording and stimulation performance in the VN of large animal models is unknown.

Methods: In anesthetized swine, we evaluated the performance of slanted, 24-electrode arrays (MEAs) for recording single fiber activity (2 animals) and for stimulation eliciting organ-specific physiological responses (2 animals) and compared MEA performance to that of multi-contact cuff electrodes (MCEs) in the same animals.

Results: We found that slanted MEAs record convincing, biphasic action potentials (APs) from single fibers (in 13/60 and 20/60 contacts in the 2 animals tested). In several cases, APs are synced to the respiratory cycle, and in rare cases to the cardiac cycle. No convincing APs are seen in recordings from MCEs. In terms of stimulation, MEAs have smaller stimulation thresholds and improved stimulation selectivity for heart, lung and laryngeal muscle responses, compared to MCEs. Stimulation through different electrodes of the MEAs evokes compound APs (recorded through MCEs) with different shapes, depending on the stimulated contact.

Conclusion: These findings provide preliminary evidence that slanted MEAs provide an effective intraneural interface for single fiber recording and function-selective stimulation in the swine VN.