RECONSTRUCTING VAGAL ANATOMY

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The vagus nerve (VN) innervates the viscera, and it is responsible for regulating their functions. Mapping the VN with the latest high-resolution imaging modalities has tremendous potential to improve the safety and efficacy of existing autonomic neuromodulation therapies and to inform design of new therapies to target or avoid specific vagal fibers. We will conduct the most comprehensive mapping of the VN to date, from the perspectives of sample size, range of imaging modalities, lengths of nerve, and imaging resolutions. We will establish a neuroanatomical repository for the vagal tissue samples, and we will validate and leverage the imaging data in computational models of vagus nerve stimulation (VNS). This work will seed and accelerate the development of novel neuromodulation therapies for autonomic regulation. We assembled an outstanding cross-cutting and experienced team that allows us to meet all the RFP criteria and exceed them in several critical areas. We will obtain high resolution data on fiber tractography, morphometry, and phenotyping using nine established and novel imaging modalities. We will focus on evaluation at justified regions of interest (ROIs; Table 1), selected based on established clinical neuromodulation sites, potential for improved selectivity (activation of target fibers and avoidance of off-target fibers), major anatomical landmarks, and surgical accessibility. We will set up and leverage our Data Analysis and Visualization Epicenter (DAVE) to ensure data validation, rigor, and timely dissemination. In our prior work, we have collected neuro-anatomical data, used these data to construct realistic computational models, designed novel cranial nerve stimulation paradigms, and translated them to humans. We are thus uniquely positioned to collect the REVA data and ensure that the data will enable development of new vagal neuromodulation therapies.