{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:46:13Z","timestamp":1790023573278,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011833","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000}}],"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OT2 OD025340; 75N98022C00018"],"award-info":[{"award-number":["OT2 OD025340; 75N98022C00018"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Peripheral nerve recordings can enhance the efficacy of neurostimulation therapies by providing a feedback signal to adjust stimulation settings for greater efficacy or reduced side effects. Computational models can accelerate the development of interfaces with high signal-to-noise ratio and selective recording. However, validation and tuning of model outputs against in vivo recordings remains computationally prohibitive due to the large number of fibers in a nerve.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We designed and implemented highly efficient modeling methods for simulating electrically evoked compound nerve action potential (CNAP) signals. The method simulated a subset of fiber diameters present in the nerve using NEURON, interpolated action potential templates across fiber diameters, and filtered the templates with a weighting function derived from fiber-specific conduction velocity and electromagnetic reciprocity outputs of a volume conductor model. We applied the methods to simulate CNAPs from rat cervical vagus nerve.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Brute force simulation of a rat vagal CNAP with all 1,759 myelinated and 13,283 unmyelinated fibers in NEURON required 286 and 15,860 CPU hours, respectively, while filtering interpolated templates required 30 and 38 seconds on a desktop computer while maintaining accuracy. Modeled CNAP amplitude could vary by over two orders of magnitude depending on tissue conductivities and cuff opening within experimentally relevant ranges. Conduction distance and fiber diameter distribution also strongly influenced the modeled CNAP amplitude, shape, and latency. Modeled and in vivo signals had comparable shape, amplitude, and latency for myelinated fibers but not for unmyelinated fibers.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Highly efficient methods of modeling neural recordings quantified the large impact that tissue properties, conduction distance, and nerve fiber parameters have on CNAPs. These methods expand the computational accessibility of neural recording models, enable efficient model tuning for validation, and facilitate the design of novel recording interfaces for neurostimulation feedback and understanding physiological systems.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pcbi.1011833","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T18:45:57Z","timestamp":1709318757000},"page":"e1011833","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Computational models of compound nerve action potentials: Efficient filter-based methods to quantify effects of tissue conductivities, conduction distance, and nerve fiber 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effects","volume":"11","author":"DTT Plachta","year":"2014","journal-title":"J Neural Eng"},{"key":"pcbi.1011833.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bios.2017.06.031","article-title":"A neural blood pressure marker for bioelectronic medicines for treatment of hypertension","volume":"98","author":"C Sevcencu","year":"2017","journal-title":"Biosens Bioelectron"},{"issue":"1","key":"pcbi.1011833.ref003","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s42234-020-00046-4","article-title":"Closed-loop bioelectronic medicine for diabetes management","volume":"6","author":"A G\u00fcemes Gonzalez","year":"2020","journal-title":"Bioelectron Med"},{"issue":"1","key":"pcbi.1011833.ref004","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s42234-019-0025-z","article-title":"Identification of hypoglycemia-specific neural signals by decoding murine vagus nerve activity","volume":"5","author":"EB 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Jiman","year":"2020","journal-title":"Sci Rep"},{"issue":"3","key":"pcbi.1011833.ref011","doi-asserted-by":"crossref","first-page":"036006","DOI":"10.1088\/1741-2552\/aa5a5b","article-title":"A micro-scale printable nanoclip for electrical stimulation and recording in small nerves","volume":"14","author":"CA Lissandrello","year":"2017","journal-title":"J Neural Eng"},{"issue":"1","key":"pcbi.1011833.ref012","doi-asserted-by":"crossref","first-page":"11723","DOI":"10.1038\/s41598-017-10639-w","article-title":"Chronic interfacing with the autonomic nervous system using carbon nanotube (CNT) yarn electrodes","volume":"7","author":"GA McCallum","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"pcbi.1011833.ref013","doi-asserted-by":"crossref","first-page":"016042","DOI":"10.1088\/1741-2552\/ab4ac4","article-title":"Selective peripheral nerve recordings from nerve cuff electrodes using convolutional neural networks","volume":"17","author":"RGL 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Tavee","year":"2019"},{"issue":"3","key":"pcbi.1011833.ref018","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1152\/ajplegacy.1927.80.3.522","article-title":"The role played by the sizes of the constituent fibers of a nerve trunk in determining the form of its action potential wave","volume":"80","author":"HS Gasser","year":"1927","journal-title":"Am J Physiol-Leg Content"},{"issue":"2","key":"pcbi.1011833.ref019","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1152\/ajplegacy.1939.127.2.393","article-title":"Axon Diameters In Relation to the Spike Dimensions and the Conduction Velocity In Mammalian A Fibers","volume":"127","author":"HS Gasser","year":"1939","journal-title":"Am J Physiol-Leg Content"},{"issue":"6","key":"pcbi.1011833.ref020","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1016\/S0006-3495(97)78890-8","article-title":"The extracellular potential of a myelinated nerve fiber in an unbounded medium and in nerve cuff models","volume":"72","author":"JJ Struijk","year":"1997","journal-title":"Biophys J"},{"issue":"2","key":"pcbi.1011833.ref021","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/BF00355258","article-title":"A volume conductor study of compound action potentials of nerves in situ: The forward problem","volume":"33","author":"DF Stegeman","year":"1979","journal-title":"Biol Cybern"},{"key":"pcbi.1011833.ref022","first-page":"57","article-title":"Compound action potential reconstructions and predicted fiber diameter distributions","volume":"52","author":"WH Olson","year":"1981","journal-title":"Prog Clin Biol Res"},{"issue":"4","key":"pcbi.1011833.ref023","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/mus.880110407","article-title":"A model of the differing change in motor and sensory action potentials over distance","volume":"11","author":"JC Kincaid","year":"1988","journal-title":"Muscle Nerve"},{"issue":"9","key":"pcbi.1011833.ref024","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/0003-9993(94)90672-6","article-title":"Waveform analysis of compound nerve action potentials: A computer simulation","volume":"75","author":"Y Okajima","year":"1994","journal-title":"Arch Phys Med Rehabil"},{"issue":"1","key":"pcbi.1011833.ref025","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/BF02368460","article-title":"A model for compound action potentials and currents in a nerve bundle I: The forward calculation","volume":"19","author":"RS Wijesinghe","year":"1991","journal-title":"Ann Biomed Eng"},{"issue":"1","key":"pcbi.1011833.ref026","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BF02368461","article-title":"A model for compound action potentials and currents in a nerve bundle II: A sensitivity analysis of model parameters for the forward and inverse calculations","volume":"19","author":"RS Wijesinghe","year":"1991","journal-title":"Ann Biomed Eng"},{"issue":"4","key":"pcbi.1011833.ref027","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/0013-4694(82)90207-3","article-title":"Modelling compound action potentials of peripheral nerves in situ. I. Model description; evidence for a non-linear relation between fibre diameter and velocity","volume":"54","author":"DF Stegeman","year":"1982","journal-title":"Electroencephalogr Clin Neurophysiol"},{"issue":"3","key":"pcbi.1011833.ref028","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1109\/TBME.1986.325718","article-title":"The Forward Problem in Electroneurography I: A Generalized Volume Conductor Model","volume":"BME-33","author":"R Schoonhoven","year":"1986","journal-title":"IEEE Trans Biomed Eng"},{"issue":"3","key":"pcbi.1011833.ref029","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1109\/TBME.1986.325719","article-title":"The Forward Problem in Electroneurography II: Comparson of Models","volume":"BME-33","author":"R Schoonhoven","year":"1986","journal-title":"IEEE Trans Biomed Eng"},{"issue":"5","key":"pcbi.1011833.ref030","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/0013-4694(82)90037-2","article-title":"Modelling compound action potentials of peripheral nerves in situ. II. A study of the influence of temperature","volume":"54","author":"DF Stegeman","year":"1982","journal-title":"Electroencephalogr Clin Neurophysiol"},{"issue":"1","key":"pcbi.1011833.ref031","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1109\/TCOMM.2018.2871121","article-title":"Capacity Analysis of a Peripheral Nerve Using Modulated Compound Action Potential Pulses","volume":"67","author":"M Donohoe","year":"2019","journal-title":"IEEE Trans Commun"},{"issue":"4","key":"pcbi.1011833.ref032","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/BF02345015","article-title":"Measurement of the performance of nerve cuff electrodes for recording","volume":"38","author":"LNS Andreasen","year":"2000","journal-title":"Med Biol Eng Comput"},{"issue":"9","key":"pcbi.1011833.ref033","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1109\/TBME.2002.800785","article-title":"Signal strength versus cuff length in nerve cuff electrode recordings","volume":"49","author":"LNS Andreasen","year":"2002","journal-title":"IEEE Trans Biomed Eng"},{"key":"pcbi.1011833.ref034","doi-asserted-by":"crossref","unstructured":"Sabetian P, Popovic MR, Yoo PB. Directionally-sensitive peripheral nerve recording: Bipolar nerve cuff design. In: 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). 2016. p. 6178\u201381.","DOI":"10.1109\/EMBC.2016.7592139"},{"key":"pcbi.1011833.ref035","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.medengphy.2016.11.010","article-title":"Characterizing the reduction of stimulation artifact noise in a tripolar nerve cuff electrode by application of a conductive shield layer","volume":"40","author":"P Sabetian","year":"2017","journal-title":"Med Eng Phys"},{"issue":"3","key":"pcbi.1011833.ref036","doi-asserted-by":"crossref","first-page":"036015","DOI":"10.1088\/1741-2552\/aa6407","article-title":"Optimizing the design of bipolar nerve cuff electrodes for improved recording of peripheral nerve activity","volume":"14","author":"P Sabetian","year":"2017","journal-title":"J Neural Eng"},{"key":"pcbi.1011833.ref037","doi-asserted-by":"crossref","unstructured":"Sabetian P, Yoo PB. Optimizing a novel nerve cuff electrode to record bidirectional neural activity. In: 2019 9th International IEEE\/EMBS Conference on Neural Engineering (NER). 2019. p. 661\u20134.","DOI":"10.1109\/NER.2019.8717079"},{"issue":"1","key":"pcbi.1011833.ref038","doi-asserted-by":"crossref","first-page":"016040","DOI":"10.1088\/1741-2552\/ab5551","article-title":"Feasibility of differentially measuring afferent and efferent neural activity with a single nerve cuff electrode","volume":"17","author":"P Sabetian","year":"2020","journal-title":"J Neural Eng"},{"issue":"1","key":"pcbi.1011833.ref039","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12021-018-9383-z","article-title":"PyPNS: Multiscale Simulation of a Peripheral Nerve in Python","volume":"17","author":"CH Lubba","year":"2019","journal-title":"Neuroinformatics"},{"issue":"3","key":"pcbi.1011833.ref040","doi-asserted-by":"crossref","first-page":"034001","DOI":"10.1088\/1361-6579\/ab08ce","article-title":"Effect of dispersion in nerve on compound action potential and impedance change: a modelling study","volume":"40","author":"I Tarotin","year":"2019","journal-title":"Physiol Meas"},{"issue":"6","key":"pcbi.1011833.ref041","doi-asserted-by":"crossref","first-page":"066020","DOI":"10.1088\/1741-2552\/ac36e2","article-title":"Computational modelling of nerve stimulation and recording with peripheral visceral neural interfaces","volume":"18","author":"CD Eiber","year":"2021","journal-title":"J Neural Eng"},{"issue":"1","key":"pcbi.1011833.ref042","doi-asserted-by":"crossref","first-page":"016013","DOI":"10.1088\/1741-2552\/14\/1\/016013","article-title":"Use of spatiotemporal templates for pathway discrimination in peripheral nerve recordings: a simulation study","volume":"14","author":"RGL Koh","year":"2017","journal-title":"J Neural Eng"},{"issue":"8","key":"pcbi.1011833.ref043","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s11517-012-0930-8","article-title":"Determination of electrode to nerve fiber distance and nerve conduction velocity through spectral analysis of the extracellular action potentials recorded from earthworm giant fibers","volume":"50","author":"S Qiao","year":"2012","journal-title":"Med Biol Eng Comput"},{"issue":"9","key":"pcbi.1011833.ref044","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1109\/TNSRE.2015.2489924","article-title":"Estimation of the Electrode-Fiber Bioelectrical Coupling From Extracellularly Recorded Single Fiber Action Potentials","volume":"24","author":"S Qiao","year":"2016","journal-title":"IEEE Trans Neural Syst Rehabil Eng"},{"issue":"4","key":"pcbi.1011833.ref045","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1113\/jphysiol.1952.sp004764","article-title":"A quantitative description of membrane current and its application to conduction and excitation in nerve","volume":"117","author":"AL Hodgkin","year":"1952","journal-title":"J Physiol"},{"issue":"9","key":"pcbi.1011833.ref046","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1152\/jn.00777.2012","article-title":"Modeling activity-dependent changes of axonal spike conduction in primary afferent C-nociceptors","volume":"111","author":"J Tigerholm","year":"2014","journal-title":"J Neurophysiol"},{"key":"pcbi.1011833.ref047","volume-title":"High-throughput segmentation of rat unmyelinated axons by deep learning","author":"LA Havton","year":"2022"},{"issue":"1","key":"pcbi.1011833.ref048","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1038\/s41598-021-82575-9","article-title":"A shape-adjusted ellipse approach corrects for varied axonal dispersion angles and myelination in primate nerve roots","volume":"11","author":"PM Bartmeyer","year":"2021","journal-title":"Sci Rep"},{"key":"pcbi.1011833.ref049","doi-asserted-by":"crossref","first-page":"601479","DOI":"10.3389\/fnins.2020.601479","article-title":"Quantified Morphology of the Cervical and Subdiaphragmatic Vagus Nerves of Human, Pig, and Rat","volume":"14","author":"NA Pelot","year":"2020","journal-title":"Front Neurosci"},{"issue":"4","key":"pcbi.1011833.ref050","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0014-4886(65)90059-2","article-title":"The specific impedance of the dorsal columns of cat: An anisotropic medium","volume":"11","author":"JB Ranck","year":"1965","journal-title":"Exp Neurol"},{"issue":"1","key":"pcbi.1011833.ref051","doi-asserted-by":"crossref","first-page":"016007","DOI":"10.1088\/1741-2552\/aaeb0c","article-title":"On the parameters used in finite element modeling of compound peripheral nerves","volume":"16","author":"NA Pelot","year":"2019","journal-title":"J Neural Eng"},{"key":"pcbi.1011833.ref052","volume-title":"Fundamentals of materials science and engineering: an integrated approach","author":"WD Callister","year":"2012","edition":"4"},{"key":"pcbi.1011833.ref053","volume-title":"Understanding the properties of matter","author":"M. 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Helmholtz","year":"1853","journal-title":"Ann Phys Chem"},{"issue":"9","key":"pcbi.1011833.ref058","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1016\/j.clinph.2005.05.018","article-title":"Model-based analysis of cortical recording with silicon microelectrodes","volume":"116","author":"MA Moffitt","year":"2005","journal-title":"Clin Neurophysiol"},{"issue":"9","key":"pcbi.1011833.ref059","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1114\/1.1310220","article-title":"Lead-field bases for electroencephalography source imaging","volume":"28","author":"D Weinstein","year":"2000","journal-title":"Ann Biomed Eng"},{"key":"pcbi.1011833.ref060","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fncom.2018.00040","article-title":"Modeling Current Sources for Neural Stimulation in COMSOL","volume":"12","author":"NA Pelot","year":"2018","journal-title":"Front Comput Neurosci"},{"issue":"1","key":"pcbi.1011833.ref061","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1088\/1741-2560\/5\/1\/005","article-title":"Analysis of the quasi-static approximation for calculating potentials generated by neural stimulation","volume":"5","author":"CA Bossetti","year":"2008","journal-title":"J Neural Eng"},{"issue":"1","key":"pcbi.1011833.ref062","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/s41598-022-04854-3","article-title":"High-throughput segmentation of unmyelinated axons by deep learning","volume":"12","author":"E Plebani","year":"2022","journal-title":"Sci Rep"},{"issue":"2","key":"pcbi.1011833.ref063","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1152\/jn.00353.2001","article-title":"Modeling the Excitability of Mammalian Nerve Fibers: Influence of Afterpotentials on the Recovery Cycle","volume":"87","author":"CC McIntyre","year":"2002","journal-title":"J Neurophysiol"},{"issue":"4","key":"pcbi.1011833.ref064","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1152\/jn.00989.2003","article-title":"Cellular Effects of Deep Brain Stimulation: Model-Based Analysis of Activation and Inhibition","volume":"91","author":"CC McIntyre","year":"2004","journal-title":"J Neurophysiol"},{"key":"pcbi.1011833.ref065","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511541612","volume-title":"The NEURON book","author":"T Carnevale","year":"2006"},{"issue":"4","key":"pcbi.1011833.ref066","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/BF01181523","article-title":"Electron microscopic serial section analysis of nodes of Ranvier in lumbar spinal roots of the cat: A morphometric study of nodal compartments in fibres of different sizes","volume":"12","author":"M Rydmark","year":"1983","journal-title":"J Neurocytol"},{"issue":"3\u20134","key":"pcbi.1011833.ref067","first-page":"145","article-title":"Ultrastructure of postnatally developing feline peripheral nodes of Ranvier","volume":"73","author":"CH Berthold","year":"1968","journal-title":"Acta Soc Med Ups"},{"issue":"Suppl 9","key":"pcbi.1011833.ref068","first-page":"37","article-title":"Ultrastructure of the node-paranode region of mature feline ventral lumbar spinal-root fibres","volume":"73","author":"CH Berthold","year":"1968","journal-title":"Acta Soc Med Ups"},{"issue":"9","key":"pcbi.1011833.ref069","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1007\/BF01989761","article-title":"Anatomy of the paranode-node-paranode region in the cat","volume":"39","author":"CH Berthold","year":"1983","journal-title":"Experientia"},{"issue":"1","key":"pcbi.1011833.ref070","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1152\/ajplegacy.1939.127.1.131","article-title":"Conduction Velocity and Diameter of Nerve Fibers","volume":"127","author":"JB Hursh","year":"1939","journal-title":"Am J Physiol-Leg Content"},{"issue":"3","key":"pcbi.1011833.ref071","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/cne.901300304","article-title":"Relation between the number of myelin lamellae and axon circumference in fibers of vagus and sciatic nerves of mice","volume":"130","author":"RL Friede","year":"1967","journal-title":"J Comp Neurol"},{"issue":"3","key":"pcbi.1011833.ref072","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1161\/01.HYP.30.3.693","article-title":"A Descriptive and Quantitative Light and Electron Microscopy Study of the Aortic Depressor Nerve in Normotensive Rats","volume":"30","author":"VPS Fazan","year":"1997","journal-title":"Hypertension"},{"issue":"3","key":"pcbi.1011833.ref073","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0304-3940(81)90165-8","article-title":"Nodal axon diameter correlates linearly with internodal axon diameter in spinal roots of the cat","volume":"24","author":"M. Rydmark","year":"1981","journal-title":"Neurosci Lett"},{"issue":"5","key":"pcbi.1011833.ref074","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1109\/TBME.1974.324406","article-title":"The active fiber in a volume conductor","volume":"BME-21","author":"R. Plonsey","year":"1974","journal-title":"IEEE Trans Biomed Eng"},{"issue":"2","key":"pcbi.1011833.ref075","doi-asserted-by":"crossref","first-page":"026005","DOI":"10.1088\/1741-2552\/ab6cb6","article-title":"In vivo quantification of excitation and kilohertz frequency block of the rat vagus nerve","volume":"17","author":"NA Pelot","year":"2020","journal-title":"J Neural Eng"},{"issue":"7","key":"pcbi.1011833.ref076","doi-asserted-by":"crossref","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"18","author":"N Percie du Sert","year":"2020","journal-title":"PLOS Biol"},{"issue":"4","key":"pcbi.1011833.ref077","doi-asserted-by":"crossref","first-page":"046048","DOI":"10.1088\/1741-2552\/abadb5","article-title":"Quantitative comparisons of block thresholds and onset responses for charge-balanced kilohertz frequency waveforms","volume":"17","author":"E Pe\u00f1a","year":"2020","journal-title":"J Neural Eng"},{"key":"pcbi.1011833.ref078","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jneumeth.2014.04.002","article-title":"Direct current contamination of kilohertz frequency alternating current waveforms","volume":"232","author":"M Franke","year":"2014","journal-title":"J Neurosci Methods"},{"issue":"1\u20132","key":"pcbi.1011833.ref079","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0165-1838(96)00038-0","article-title":"Preservation of the cervical vagus nerve in aged rats: morphometric and enzyme histochemical evidence","volume":"60","author":"N Soltanpour","year":"1996","journal-title":"J Auton Nerv Syst"},{"issue":"2","key":"pcbi.1011833.ref080","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/0306-4522(91)90402-A","article-title":"A proposed relationship between circumference and conduction velocity of unmyelinated axons from normal and regenerated cat hindlimb cutaneous nerves","volume":"42","author":"B Hoffmeister","year":"1991","journal-title":"Neuroscience"},{"issue":"880","key":"pcbi.1011833.ref081","first-page":"323","article-title":"The thickness of the myelin sheaths of normal and regenerating peripheral nerve fibres","volume":"135","author":"FK Sanders","year":"1947","journal-title":"Proc R Soc Lond Ser B\u2014Biol Sci"},{"issue":"1","key":"pcbi.1011833.ref082","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1113\/jphysiol.1979.sp012737","article-title":"Scaling factor relating conduction velocity and diameter for myelinated afferent nerve fibres in the cat hind limb","volume":"289","author":"IA Boyd","year":"1979","journal-title":"J Physiol"},{"issue":"1","key":"pcbi.1011833.ref083","doi-asserted-by":"crossref","first-page":"23831","DOI":"10.1038\/s41598-021-03248-1","article-title":"Human organ donor-derived vagus nerve biopsies allow for well-preserved ultrastructure and high-resolution mapping of myelinated and unmyelinated fibers","volume":"11","author":"LA Havton","year":"2021","journal-title":"Sci Rep"},{"issue":"4","key":"pcbi.1011833.ref084","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/ar.1091310404","article-title":"The myelinated component of the vagus nerves in man","volume":"131","author":"HN Schnitzlein","year":"1958","journal-title":"Anat Rec"},{"issue":"2","key":"pcbi.1011833.ref085","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0006-3495(84)84009-6","article-title":"AC impedance of the perineurium of the frog sciatic nerve","volume":"46","author":"A Weerasuriya","year":"1984","journal-title":"Biophys J"},{"issue":"4","key":"pcbi.1011833.ref086","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/aor.14500","article-title":"Characterization of the electrical properties of mammalian peripheral nerve laminae","volume":"47","author":"MR Horn","year":"2023","journal-title":"Artif Organs"},{"issue":"2","key":"pcbi.1011833.ref087","doi-asserted-by":"crossref","first-page":"026032","DOI":"10.1088\/1741-2552\/acc42b","article-title":"Fibers in smaller fascicles have lower activation thresholds with cuff electrodes due to thinner perineurium and smaller cross-sectional area","volume":"20","author":"CJ Davis","year":"2023","journal-title":"J Neural Eng"},{"issue":"3","key":"pcbi.1011833.ref088","doi-asserted-by":"crossref","first-page":"036032","DOI":"10.1088\/1741-2552\/acda64","article-title":"Validated computational models predict vagus nerve stimulation thresholds in preclinical animals and humans","volume":"20","author":"ED Musselman","year":"2023","journal-title":"J Neural Eng"},{"issue":"1","key":"pcbi.1011833.ref089","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1152\/jn.00315.2020","article-title":"Excitation properties of computational models of unmyelinated peripheral axons","volume":"125","author":"NA Pelot","year":"2021","journal-title":"J 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