ANCILLARY PROJECT 1 Abstract: Microelectrode Recordings from the Vagus Nerve in Awake Humans The vagus nerve, the longest cranial nerve, supplies structures in the neck, thorax, and abdomen with sensory and motor innervation, including parasympathetic innervation to the heart, lungs, airways, and gut. Unlike the sympathetic nervous system, in which it has been possible to make direct microelectrode recordings in humans for >50 years, it has not been possible to record parasympathetic outflow directly – until now. We developed an ultrasound-guided approach that allows us to record directly from the vagus nerve via a microelectrode inserted percutaneously into the neck of awake humans. In this Ancillary Project, we plan to build upon our preliminary data from this approach by undertaking a detailed neurophysiological investigation of the human vagus nerve and identifying the nerve fibers activated during vagal nerve stimulation, both sensory and motor (including parasympathetic) axons. This may provide a specified range of stimulus intensities required to excite myelinated and unmyelinated nerve fibers in the Clinical Study Protocol as described in the Clinical Core. It will also provide unprecedented detail into the physiology of the human vagus nerve and inform future development of novel intrafascicular neural interfaces.