Publications

Background: Vagal nerve fibers traveling in distinct fascicles innervate different organs and regulate specific functions. Current vagus nerve stimulation (VNS) therapies activate vagal fibers non-selectively, often resulting in reduced efficacy and side effects. Objective: To characterize the anatomical organization of vagal fibers and demonstrate fascicle-selective VNS. Methods: We used quantified immunohistochemistry, micro-computed tomography imaging, and multi-contact cuff electrodes to map fascicular organization and perform selective stimulation in swine. Results: Myelinated afferents and efferents occupy separate fascicles. Larynx-, heart-, and lung-specific fascicles are spatially separated and progressively merge. Fascicle-selective VNS elicited organ-specific physiological responses with radially asymmetric compound action potentials. Conclusions: Fascicular VNS enables selective modulation of specific organs and functions, offering improved efficacy and reduced off-target effects compared to conventional non-selective VNS.

Quantitative descriptions of the morphology and structure of peripheral nerves is central in the development of bioelectronic devices interfacing nerves. While histological procedures and microscopy techniques yield high-resolution detailed images of individual axons, automated methods to extract relevant information at the single-axon level are not widely available. A segmentation algorithm was implemented that allows for feature extraction in immunohistochemistry (IHC) images of peripheral nerves at the single fiber scale. Features extracted include short and long cross-sectional diameters, area, perimeter, thickness of surrounding myelin and polar coordinates of single axons within a nerve or nerve fascicle. The algorithm was evaluated using manually annotated IHC images of 27 fascicles of the swine cervical vagus; the accuracy of single-axon detection was 82%, and the classification accuracy of fiber myelination was 89%.