Organotopic organization of the porcine mid-cervical vagus nerve

Nicole Thompson; Enrico Ravagli; Svetlana Mastitskaya; Francesco Iacoviello; Thaleia-Rengina Stathopoulou; Justin Perkins; Paul R Shearing; Kirill Aristovich; David Holder

doi:10.3389/fnins.2023.963503

Organotopic organization of the porcine mid-cervical vagus nerve

Front Neurosci. 2023 May 2:17:963503. doi: 10.3389/fnins.2023.963503. eCollection 2023.

Authors

Nicole Thompson¹, Enrico Ravagli¹, Svetlana Mastitskaya¹, Francesco Iacoviello², Thaleia-Rengina Stathopoulou³, Justin Perkins³, Paul R Shearing², Kirill Aristovich¹, David Holder¹

Affiliations

¹ Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom.
² Electrochemical Innovations Lab, Department of Chemical Engineering, University College London, London, United Kingdom.
³ Department of Clinical Science and Services, The Royal Veterinary College, Hatfield, United Kingdom.

Abstract

Introduction: Despite detailed characterization of fascicular organization of somatic nerves, the functional anatomy of fascicles evident in human and large mammal cervical vagus nerve is unknown. The vagus nerve is a prime target for intervention in the field of electroceuticals due to its extensive distribution to the heart, larynx, lungs, and abdominal viscera. However, current practice of the approved vagus nerve stimulation (VNS) technique is to stimulate the entire nerve. This produces indiscriminate stimulation of non-targeted effectors and undesired side effects. Selective neuromodulation is now a possibility with a spatially-selective vagal nerve cuff. However, this requires the knowledge of the fascicular organization at the level of cuff placement to inform selectivity of only the desired target organ or function.

Methods and results: We imaged function over milliseconds with fast neural electrical impedance tomography and selective stimulation, and found consistent spatially separated regions within the nerve correlating with the three fascicular groups of interest, suggesting organotopy. This was independently verified with structural imaging by tracing anatomical connections from the end organ with microCT and the development of an anatomical map of the vagus nerve. This confirmed organotopic organization.

Discussion: Here we show, for the first time, localized fascicles in the porcine cervical vagus nerve which map to cardiac, pulmonary and recurrent laryngeal function (N = 4). These findings pave the way for improved outcomes in VNS as unwanted side effects could be reduced by targeted selective stimulation of identified organ-specific fiber-containing fascicles and the extension of this technique clinically beyond the currently approved disorders to treat heart failure, chronic inflammatory disorders, and more.

Keywords: fascicles; fascicular anatomy; neuroanatomy; neuromodulation; neurophysiology; organotopic organization; selective stimulation; vagus nerve.