Laterality, sexual dimorphism, and human vagal projectome heterogeneity shape neuromodulation to vagus nerve stimulation

dc.contributor.authorBiscola, Natalia P.
dc.contributor.authorBartmeyer, Petra M.
dc.contributor.authorBeshay, Youssef
dc.contributor.authorStern, Esther
dc.contributor.authorMihaylov, Plamen V.
dc.contributor.authorPowley, Terry L.
dc.contributor.authorWard, Matthew P.
dc.contributor.authorHavton, Leif A.
dc.contributor.departmentSurgery, School of Medicine
dc.date.accessioned2024-12-11T12:48:54Z
dc.date.available2024-12-11T12:48:54Z
dc.date.issued2024-11-19
dc.description.abstractNeuromodulation by vagus nerve stimulation (VNS) provides therapeutic benefits in multiple medical conditions, including epilepsy and clinical depression, but underlying mechanisms of action are not well understood. Cervical vagus nerve biopsies were procured from transplant organ donors for high resolution light microscopy (LM) and transmission electron microscopy (TEM) to map the human fascicular and sub-fascicular organization. Cervical vagal segments show laterality with right sided dominance in fascicle numbers and cross-sectional areas as well as sexual dimorphism with female dominance in fascicle numbers. The novel and unprecedented detection of numerous small fascicles by high resolution LM and TEM expand the known fascicle size range and morphological diversity of the human vagus nerve. Ground truth TEM quantification of all myelinated and unmyelinated axons within individual nerve fascicles show marked sub-fascicular heterogeneity of nerve fiber numbers, size, and myelination. A heuristic action potential interpreter (HAPI) tool predicts VNS-evoked compound nerve action potentials (CNAPs) generated by myelinated and unmyelinated nerve fibers and validates functional dissimilarity between fascicles. Our findings of laterality, sexual dimorphism, and an expanded range of fascicle size heterogeneity provide mechanistic insights into the varied therapeutic responses and off-target effects to VNS and may guide new refinement strategies for neuromodulation.
dc.eprint.versionFinal published version
dc.identifier.citationBiscola NP, Bartmeyer PM, Beshay Y, et al. Laterality, sexual dimorphism, and human vagal projectome heterogeneity shape neuromodulation to vagus nerve stimulation. Commun Biol. 2024;7(1):1536. Published 2024 Nov 19. doi:10.1038/s42003-024-07222-1
dc.identifier.urihttps://hdl.handle.net/1805/44935
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s42003-024-07222-1
dc.relation.journalCommunications Biology
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.sourcePMC
dc.subjectAction potentials
dc.subjectFunctional laterality
dc.subjectSex characteristics
dc.subjectVagus nerve stimulation
dc.titleLaterality, sexual dimorphism, and human vagal projectome heterogeneity shape neuromodulation to vagus nerve stimulation
dc.typeArticle
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