{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T20:20:01Z","timestamp":1776111601847,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010556","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000}}],"reference-count":127,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Skempton Scholarship"},{"name":"Imperial College Research Fellowship"},{"name":"UNSW Scientia Fellowship"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Our understanding of the firing behaviour of motoneuron (MN) pools during human voluntary muscle contractions is currently limited to electrophysiological findings from animal experiments extrapolated to humans, mathematical models of MN pools not validated for human data, and experimental results obtained from decomposition of electromyographical (EMG) signals. These approaches are limited in accuracy or provide information on only small partitions of the MN population. Here, we propose a method based on the combination of high-density EMG (HDEMG) data and realistic modelling for predicting the behaviour of entire pools of motoneurons in humans. The method builds on a physiologically realistic model of a MN pool which predicts, from the experimental spike trains of a smaller number of individual MNs identified from decomposed HDEMG signals, the unknown recruitment and firing activity of the remaining unidentified MNs in the complete MN pool. The MN pool model is described as a cohort of single-compartment leaky fire-and-integrate (LIF) models of MNs scaled by a physiologically realistic distribution of MN electrophysiological properties and driven by a spinal synaptic input, both derived from decomposed HDEMG data. The MN spike trains and effective neural drive to muscle, predicted with this method, have been successfully validated experimentally. A representative application of the method in MN-driven neuromuscular modelling is also presented. The proposed approach provides a validated tool for neuroscientists, experimentalists, and modelers to infer the firing activity of MNs that cannot be observed experimentally, investigate the neuromechanics of human MN pools, support future experimental investigations, and advance neuromuscular modelling for investigating the neural strategies controlling human voluntary contractions.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010556","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T16:11:37Z","timestamp":1664467897000},"page":"e1010556","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Estimation of the firing behaviour of a complete motoneuron pool by combining electromyography signal decomposition and realistic motoneuron modelling"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6146-1829","authenticated-orcid":true,"given":"Arnault H.","family":"Caillet","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-0145","authenticated-orcid":true,"given":"Andrew T. M.","family":"Phillips","sequence":"additional","affiliation":[]},{"given":"Dario","family":"Farina","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1402-5359","authenticated-orcid":true,"given":"Luca","family":"Modenese","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"pcbi.1010556.ref001","doi-asserted-by":"crossref","first-page":"578504","DOI":"10.3389\/fneur.2020.578504","article-title":"Surface Electromyography: What Limits Its Use in Exercise and Sport Physiology?","volume":"11","author":"F Felici","year":"2020","journal-title":"Frontiers in neurology"},{"issue":"3","key":"pcbi.1010556.ref002","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1249\/JES.0000000000000254","article-title":"Novel Insights Into Biarticular Muscle Actions Gained From High-Density Electromyogram.","volume":"49","author":"K Watanabe","year":"2021","journal-title":"Exercise and sport 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laterality of motor unit behavior in female patients with parkinson\u2019s disease using high-density surface electromyography","volume":"53","author":"Y Nishikawa","year":"2021","journal-title":"European Journal of Neuroscience"},{"issue":"2","key":"pcbi.1010556.ref009","doi-asserted-by":"crossref","first-page":"e56013","DOI":"10.1371\/journal.pone.0056013","article-title":"A computational model of torque generation: neural, contractile, metabolic and musculoskeletal components.","volume":"8","author":"DM Callahan","year":"2013","journal-title":"PloS one"},{"key":"pcbi.1010556.ref010","doi-asserted-by":"crossref","first-page":"103480","DOI":"10.1016\/j.compbiomed.2019.103480","article-title":"Multiscale Hill-type modeling of the mechanical muscle behavior driven by the neural drive in isometric conditions.","volume":"115","author":"V Carriou","year":"2019","journal-title":"Computers in biology and 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in motor unit discharge are related to changes in fascicle length during isometric contractions.","author":"E Martinez-Valdes","year":"2021","journal-title":"Cold Spring Harbor Laboratory"},{"key":"pcbi.1010556.ref015","doi-asserted-by":"crossref","first-page":"101637","DOI":"10.1016\/j.bspc.2019.101637","article-title":"Hand gesture recognition based on motor unit spike trains decoded from high-density electromyography.","volume":"55","author":"C Chen","year":"2020","journal-title":"Biomedical signal processing and control."},{"key":"pcbi.1010556.ref016","first-page":"1","article-title":"Toward higher-performance bionic limbs for wider clinical use","author":"D Farina","year":"2021","journal-title":"Nature biomedical engineering"},{"issue":"2","key":"pcbi.1010556.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41551-016-0025","article-title":"Man\/machine interface based on the discharge timings of spinal motor neurons after targeted muscle 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Heckman","year":"2012","journal-title":"Compr. 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Wiley interdisciplinary reviews.","volume":"11","author":"O R\u00f6hrle","year":"2019","journal-title":"Systems biology and medicine"},{"key":"pcbi.1010556.ref036","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.brainres.2009.06.101","article-title":"A nerve model of greatly increased energy-efficiency and encoding flexibility over the Hodgkin\u2013Huxley model","volume":"1296","author":"JF Fohlmeister","year":"2009","journal-title":"Brain research"},{"issue":"3","key":"pcbi.1010556.ref037","doi-asserted-by":"crossref","first-page":"H1378","DOI":"10.1152\/ajpheart.00185.2003","article-title":"Computer model of action potential of mouse ventricular myocytes","volume":"287","author":"VE Bondarenko","year":"2004","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"issue":"7","key":"pcbi.1010556.ref038","first-page":"284","article-title":"Predicting action potential characteristics of human auditory nerve fibres through modification of the Hodgkin-Huxley equations","volume":"104","author":"JE Smit","year":"2008","journal-title":"South African Journal of Science"},{"issue":"4","key":"pcbi.1010556.ref039","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1152\/jn.00041.2018","article-title":"A model of the rat medial gastrocnemius muscle based on inputs to motoneurons and on an algorithm for prediction of the motor unit force","volume":"120","author":"R Raikova","year":"2018","journal-title":"Journal of neurophysiology"},{"issue":"1","key":"pcbi.1010556.ref040","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1152\/physiol.00026.2019","article-title":"Nonlinear input-output functions of motoneurons.","volume":"35","author":"MD Binder","year":"2020","journal-title":"Physiology"},{"issue":"3","key":"pcbi.1010556.ref041","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1152\/jn.00850.2016","article-title":"Synaptic control of the shape of the motoneuron pool input-output function","volume":"117","author":"RK Powers","year":"2017","journal-title":"Journal of neurophysiology"},{"key":"pcbi.1010556.ref042","doi-asserted-by":"crossref","first-page":"e76489","DOI":"10.7554\/eLife.76489","article-title":"Mathematical relationships between spinal motoneuron properties.","volume":"11","author":"AH Caillet","year":"2022","journal-title":"eLife"},{"issue":"1","key":"pcbi.1010556.ref043","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-02717-4","article-title":"Generalized leaky integrate-and-fire models classify multiple neuron types","volume":"9","author":"C Teeter","year":"2018","journal-title":"Nat. Commun"},{"issue":"1","key":"pcbi.1010556.ref044","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00422-006-0068-6","article-title":"A review of the integrate-and-fire neuron model: I. Homogeneous synaptic input.","volume":"95","author":"AN Burkitt","year":"2006","journal-title":"Biological cybernetics."},{"issue":"5","key":"pcbi.1010556.ref045","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1109\/TNN.2004.832719","article-title":"Which model to use for cortical spiking neurons?","volume":"15","author":"EM Izhikevich","year":"2004","journal-title":"IEEE Transactions on Neural Networks"},{"issue":"11","key":"pcbi.1010556.ref046","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1162\/NECO_a_00196","article-title":"Estimating parameters of generalized integrate-and-fire neurons from the maximum likelihood of spike trains.","volume":"23","author":"Y Dong","year":"2011","journal-title":"Neural computation."},{"issue":"19","key":"pcbi.1010556.ref047","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1113\/JP271748","article-title":"The human motor neuron pools receive a dominant slow-varying common synaptic input","volume":"594","author":"F Negro","year":"2016","journal-title":"J. Physiol"},{"issue":"3287","key":"pcbi.1010556.ref048","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1126\/science.126.3287.1345","article-title":"Relation between Size of Neurons and Their Susceptibility to Discharge","volume":"126","author":"E. Henneman","year":"1957","journal-title":"Science"},{"issue":"3","key":"pcbi.1010556.ref049","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1152\/jn.1965.28.3.599","article-title":"Excitability and inhibitibility of motoneurons of different sizes","volume":"28","author":"E Henneman","year":"1965","journal-title":"J Neurophysiol"},{"issue":"3","key":"pcbi.1010556.ref050","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1152\/jn.1965.28.3.560","article-title":"Functional significance of cell size in spinal motoneurons","volume":"28","author":"E Henneman","year":"1965","journal-title":"J Neurophysiol"},{"issue":"6","key":"pcbi.1010556.ref051","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1152\/jn.1974.37.6.1338","article-title":"Rank order of motoneurons within a pool: law of combination","volume":"37","author":"E Henneman","year":"1974","journal-title":"J Neurophysiol"},{"key":"pcbi.1010556.ref052","first-page":"26","article-title":"Recruitment of motoneurons: The size principle","author":"E. Henneman","year":"1981","journal-title":"Motor Unit Types, Recruitment and Plasticity in Health and Disease"},{"issue":"1","key":"pcbi.1010556.ref053","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1242\/jeb.115.1.105","article-title":"The size-principle: a deterministic output emerges from a set of probabilistic connections","volume":"115","author":"E. Henneman","year":"1985","journal-title":"J. Exp. Biol"},{"key":"pcbi.1010556.ref054","doi-asserted-by":"crossref","first-page":"102548","DOI":"10.1016\/j.jelekin.2021.102548","article-title":"Analysis of motor unit spike trains estimated from high-density surface electromyography is highly reliable across operators","volume":"58","author":"F Hug","year":"2021","journal-title":"Journal of Electromyography and Kinesiology"},{"issue":"2","key":"pcbi.1010556.ref055","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1152\/japplphysiol.00635.2020","article-title":"Muscles from the same muscle group do not necessarily share common drive: evidence from the human triceps surae","volume":"130","author":"F Hug","year":"2021","journal-title":"Journal of applied physiology"},{"issue":"1","key":"pcbi.1010556.ref056","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1113\/jphysiol.1982.sp014293","article-title":"Behaviour of human motor units in different muscles during linearly varying contractions","volume":"329","author":"CJ De Luca","year":"1982","journal-title":"J. Physiol"},{"issue":"2","key":"pcbi.1010556.ref057","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1159\/000140989","article-title":"Morphologic studies of motor units in normal human muscles.","volume":"23","author":"B Feinstein","year":"1955","journal-title":"Cells Tissues Organs"},{"issue":"4","key":"pcbi.1010556.ref058","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/00131402-200206000-00001","article-title":"Motor unit estimate number in the anterior tibial muscle: normative data versus findings in critically ill patients in intensive care units","volume":"3","author":"W Trojaborg","year":"2002","journal-title":"Journal of clinical neuromuscular disease"},{"issue":"5","key":"pcbi.1010556.ref059","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.clinph.2009.02.168","article-title":"Inter-rater reliability of motor unit number estimates and quantitative motor unit analysis in the tibialis anterior muscle.","volume":"120","author":"SG Boe","year":"2009","journal-title":"Clinical neurophysiology."},{"issue":"9","key":"pcbi.1010556.ref060","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1249\/MSS.0b013e3181d6f9e9","article-title":"Motor unit number estimates in masters runners: use it or lose it.","volume":"42","author":"GA Power","year":"2010","journal-title":"Med Sci Sports Exerc"},{"issue":"19","key":"pcbi.1010556.ref061","doi-asserted-by":"crossref","first-page":"e12987","DOI":"10.14814\/phy2.12987","article-title":"Motor unit number estimates and neuromuscular transmission in the tibialis anterior of master athletes: evidence that athletic older people are not spared from age-related motor unit remodeling.","volume":"4","author":"M Piasecki","year":"2016","journal-title":"Physiological reports."},{"issue":"12","key":"pcbi.1010556.ref062","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1016\/j.clinph.2015.02.002","article-title":"Increased motor unit potential shape variability across consecutive motor unit discharges in the tibialis anterior and vastus medialis muscles of healthy older subjects.","volume":"126","author":"ML Hourigan","year":"2015","journal-title":"Clinical Neurophysiology"},{"issue":"4","key":"pcbi.1010556.ref063","first-page":"461","article-title":"Motor unit number estimates in the tibialis anterior muscle of young, old, and very old men. Muscle & Nerve","volume":"31","author":"CJ McNeil","year":"2005","journal-title":"Official Journal of the American Association of Electrodiagnostic Medicine"},{"issue":"6","key":"pcbi.1010556.ref064","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1139\/h97-038","article-title":"Mechanical properties and behaviour of motor units in the tibialis anterior during voluntary contractions. Can","volume":"22","author":"M Van Cutsem","year":"1997","journal-title":"J. Appl. Physiol"},{"issue":"10","key":"pcbi.1010556.ref065","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/sc.2008.7","article-title":"Motor unit number estimation of the tibialis anterior muscle in spinal cord injury.","volume":"46","author":"GX Xiong","year":"2008","journal-title":"Spinal Cord."},{"issue":"6","key":"pcbi.1010556.ref066","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/mus.24442","article-title":"Motor unit number estimation: a technology and literature review.","volume":"50","author":"CL Gooch","year":"2014","journal-title":"Muscle & nerve"},{"issue":"2","key":"pcbi.1010556.ref067","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/BF01042285","article-title":"Distribution of different fibre types in human skeletal muscles. I. Method for the preparation and analysis of cross-sections of whole tibialis anterior.","volume":"15","author":"KB Henriksson-Lars\u00e9n","year":"1983","journal-title":"The Histochemical journal."},{"issue":"3","key":"pcbi.1010556.ref068","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1748-1716.1985.tb07583.x","article-title":"Distribution, number and size of different types of fibres in whole cross-sections of female m tibialis anterior. An enzyme histochemical study","volume":"123","author":"K Henriksson-Lars\u00e9n","year":"1985","journal-title":"Acta Physiologica Scandinavica"},{"issue":"2","key":"pcbi.1010556.ref069","first-page":"65","article-title":"American Journal of Physical Medicine & Rehabilitation","volume":"38","author":"E. Christensen","year":"1959","journal-title":"American Journal of Physical Medicine & Rehabilitation"},{"issue":"3","key":"pcbi.1010556.ref070","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.jbiomech.2013.12.002","article-title":"Relationships of 35 lower limb muscles to height and body mass quantified using MRI","volume":"47","author":"GG Handsfield","year":"2014","journal-title":"Journal of Biomechanics"},{"issue":"1","key":"pcbi.1010556.ref071","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1469-7793.1998.295by.x","article-title":"Changes in single motor unit behaviour contribute to the increase in contraction speed after dynamic training in humans","volume":"513","author":"M Van Cutsem","year":"1998","journal-title":"The Journal of physiology"},{"issue":"1","key":"pcbi.1010556.ref072","doi-asserted-by":"crossref","first-page":"117.123","DOI":"10.1007\/PL00005610","article-title":"Motor unit recruitment order during voluntary and electrically induced contractions in the tibialis anterior","volume":"114","author":"P Feiereisen","year":"1997","journal-title":"Experimental brain research"},{"issue":"3","key":"pcbi.1010556.ref073","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1113\/jphysiol.1977.sp011689","article-title":"Ballistic contractions in man: characteristic recruitment pattern of single motor units of the tibialis anterior muscle","volume":"264","author":"JE Desmedt","year":"1977","journal-title":"The Journal of physiology"},{"issue":"1","key":"pcbi.1010556.ref074","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1113\/jphysiol.1987.sp016756","article-title":"Muscle fibre conduction velocity in motor units of the human anterior tibial muscle: a new size principle parameter","volume":"391","author":"S Andreassen","year":"1987","journal-title":"J. Physiol"},{"issue":"1","key":"pcbi.1010556.ref075","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1007\/BF00231776","article-title":"The effect of muscle length on motor unit discharge characteristics in human tibialis anterior muscle","volume":"84","author":"DW Vander Linden","year":"1991","journal-title":"Experimental brain research"},{"issue":"2","key":"pcbi.1010556.ref076","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1152\/jappl.1999.87.2.843","article-title":"Motor unit firing rates and contractile properties in tibialis anterior of young and old men","volume":"87","author":"DM Connelly","year":"1999","journal-title":"Journal of applied physiology"},{"key":"pcbi.1010556.ref077","unstructured":"Ankit R. WebPlotDigitizer. (4.4) Pacifica, California, USA: 2020."},{"issue":"1","key":"pcbi.1010556.ref078","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1113\/jphysiol.1979.sp012643","article-title":"\u2019Donovan MJ, Stephens JA, Taylor A. 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Kernell","year":"1966","journal-title":"Science"},{"issue":"5","key":"pcbi.1010556.ref087","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1152\/jn.1985.53.5.1323","article-title":"Membrane electrical properties and prediction of motor-unit type of medial gastrocnemius motoneurons in the cat","volume":"53","author":"JE Zengel","year":"1985","journal-title":"J Neurophysiol"},{"issue":"6","key":"pcbi.1010556.ref088","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1152\/jn.1981.46.6.1326","article-title":"Rheobase, input resistance, and motor-unit type in medial gastrocnemius motoneurons in the cat","volume":"46","author":"JW Fleshman","year":"1981","journal-title":"J Neurophysiol"},{"issue":"1","key":"pcbi.1010556.ref089","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1113\/jphysiol.1993.sp019596","article-title":"Matching between motoneurone and muscle unit properties in rat medial gastrocnemius","volume":"463","author":"R Bakels","year":"1993","journal-title":"J. Physiol"},{"issue":"1","key":"pcbi.1010556.ref090","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0006-8993(81)90756-3","article-title":"Threshold current for repetitive impulse firing in motoneurones innervating muscle fibres of different fatigue sensitivity in the cat","volume":"229","author":"D Kernell","year":"1981","journal-title":"Brain Res"},{"issue":"4","key":"pcbi.1010556.ref091","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1152\/jn.1987.57.4.1227","article-title":"Motor-unit properties following cross-reinnervation of cat lateral gastrocnemius and soleus muscles with medial gastrocnemius nerve. II. Influence of muscle on motoneurons","volume":"57","author":"RC Foehring","year":"1987","journal-title":"J Neurophysiol"},{"issue":"4","key":"pcbi.1010556.ref092","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1152\/jn.1993.69.4.1160","article-title":"Physiological properties of motoneurons innervating different muscle unit types in rat gastrocnemius","volume":"69","author":"PF Gardiner","year":"1993","journal-title":"J Neurophysiol"},{"issue":"2","key":"pcbi.1010556.ref093","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1152\/jn.1998.80.2.583","article-title":"Bistability in Spinal Motoneurons In Vivo: Systematic Variations in Persistent Inward Currents","volume":"80","author":"RH Lee","year":"1998","journal-title":"Journal of neurophysiology"},{"issue":"2","key":"pcbi.1010556.ref094","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1152\/jn.1998.80.2.572","article-title":"Bistability in spinal motoneurons in vivo: systematic variations in rhythmic firing patterns","volume":"80","author":"RH Lee","year":"1998","journal-title":"Journal of neurophysiology"},{"issue":"6","key":"pcbi.1010556.ref095","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S0021-9290(03)00010-1","article-title":"An EMG-driven musculoskeletal model to estimate muscle forces and knee joint moments in vivo","volume":"36","author":"DG Lloyd","year":"2003","journal-title":"Journal of Biomechanics"},{"issue":"7","key":"pcbi.1010556.ref096","doi-asserted-by":"crossref","first-page":"e1006223","DOI":"10.1371\/journal.pcbi.1006223","article-title":"OpenSim: Simulating musculoskeletal dynamics and neuromuscular control to study human and animal movement.","volume":"14","author":"A Seth","year":"2018","journal-title":"PLoS computational biology."},{"issue":"10","key":"pcbi.1010556.ref097","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1109\/TBME.2016.2586891","article-title":"Full-Body Musculoskeletal Model for Muscle-Driven Simulation of Human Gait","volume":"63","author":"A Rajagopal","year":"2016","journal-title":"IEEE Transactions on Biomedical Engineering"},{"key":"pcbi.1010556.ref098","unstructured":"Hatze H. Myocybernetic control models of skeletal muscle - characteristics and applications. b ed.: University of South Africa Press, Pretoria; 1980."},{"issue":"5","key":"pcbi.1010556.ref099","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1152\/jn.1986.55.5.947","article-title":"Properties of self-reinnervated motor units of medial gastrocnemius of cat. II. 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Physiol"},{"issue":"1","key":"pcbi.1010556.ref102","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/cne.902090103","article-title":"An HRP study of the relation between cell size and motor unit type in cat ankle extensor motoneurons","volume":"209","author":"RE Burke","year":"1982","journal-title":"J. Comp. Neurol"},{"issue":"4","key":"pcbi.1010556.ref103","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/cne.902020409","article-title":"A quantitative light microscopic study of the dendrites of cat spinal \u03b1-motoneurons after intracellular staining with horseradish peroxidase","volume":"202","author":"Kellerth JO Ulfhake","year":"1981","journal-title":"J. Comp. Neurol"},{"issue":"1","key":"pcbi.1010556.ref104","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0006-8993(84)90471-2","article-title":"Electrophysiological and morphological measurements in cat gastrocnemius and soleus \u03b1-motoneurones","volume":"307","author":"B Ulfhake","year":"1984","journal-title":"Brain Res"},{"issue":"1","key":"pcbi.1010556.ref105","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/cne.902780107","article-title":"Postnatal development of cat hind limb motoneurons. III: Changes in size of motoneurons supplying the triceps surae muscle","volume":"278","author":"B Ulfhake","year":"1988","journal-title":"Journal of comparative neurology (1911)."},{"issue":"2","key":"pcbi.1010556.ref106","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1113\/jphysiol.1974.sp010570","article-title":"Specific membrane properties of cat motoneurones","volume":"239","author":"JN Barrett","year":"1974","journal-title":"J. Physiol"},{"issue":"1","key":"pcbi.1010556.ref107","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1113\/jphysiol.1984.sp015473","article-title":"Relations among passive electrical properties of lumbar alpha-motoneurones of the cat","volume":"356","author":"Gustafsson","year":"1984","journal-title":"J. Physiol"},{"issue":"2","key":"pcbi.1010556.ref108","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1152\/jn.01018.2009","article-title":"Relationship between firing rate and recruitment threshold of motoneurons in voluntary isometric contractions","volume":"104","author":"CJ De Luca","year":"2010","journal-title":"Journal of neurophysiology"},{"issue":"1","key":"pcbi.1010556.ref109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-62773-7","article-title":"Neuro-musculoskeletal mapping for man-machine interfacing.","volume":"10","author":"T Kapelner","year":"2020","journal-title":"Scientific reports."},{"issue":"14","key":"pcbi.1010556.ref110","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1113\/JP276153","article-title":"Robust and accurate decoding of motoneuron behaviour and prediction of the resulting force output","volume":"596","author":"CK Thompson","year":"2018","journal-title":"The Journal of physiology"},{"issue":"4412","key":"pcbi.1010556.ref111","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/173971a0","article-title":"Structural changes in muscle during contraction: interference microscopy of living muscle fibres","volume":"173","author":"AF Huxley","year":"1954","journal-title":"Nature"},{"key":"pcbi.1010556.ref112","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0096-4174(18)30128-8","article-title":"Muscle structure and theories of contraction","volume":"7","author":"AF Huxley","year":"1957","journal-title":"Prog.Biophys.Biophys.Chem"},{"issue":"11","key":"pcbi.1010556.ref113","first-page":"747,755","article-title":"EMG to force processing I: An electrical analogue of the hill muscle model","volume":"14","author":"AL Hof","year":"1981","journal-title":"Journal of biomechanics"},{"issue":"4","key":"pcbi.1010556.ref114","first-page":"359","article-title":"Muscle and Tendon: Properties, Models, Scaling, And Application To Biomechanics And Motor Control","volume":"17","author":"E. Zajac Felix","year":"1989","journal-title":"Critical reviews in biomedical engineering"},{"issue":"1","key":"pcbi.1010556.ref115","doi-asserted-by":"crossref","first-page":"13465","DOI":"10.1038\/s41598-017-13766-6","article-title":"In Vivo Neuromechanics: Decoding Causal Motor Neuron Behavior with Resulting Musculoskeletal Function.","volume":"7","author":"M Sartori","year":"2017","journal-title":"Scientific reports"},{"key":"pcbi.1010556.ref116","first-page":"1643","article-title":"Comparison of human gastrocnemius forces predicted by Hill-type muscle models and estimated from ultrasound images","author":"TJM Dick","year":"2017","journal-title":"Journal of experimental biology"},{"issue":"2","key":"pcbi.1010556.ref117","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00337268","article-title":"A myocybernetic control model of skeletal muscle.","volume":"25","author":"H. Hatze","year":"1977","journal-title":"Biological cybernetics."},{"issue":"1","key":"pcbi.1010556.ref118","doi-asserted-by":"crossref","first-page":"011002","DOI":"10.1115\/1.4051718","article-title":"A New Muscle Activation Dynamics Model, That Simulates the Calcium Kinetics and Incorporates the Role of Store-Operated Calcium Entry Channels, to Enhance the Electromyography-Driven Hill-Type Models","volume":"144","author":"M Hussein","year":"2021","journal-title":"Journal of Biomechanical Engineering"},{"issue":"2","key":"pcbi.1010556.ref119","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1109\/86.593289","article-title":"A nonlinear mathematical model of electrically stimulated skeletal muscle","volume":"5","author":"SJ Dorgan","year":"1997","journal-title":"IEEE transactions on rehabilitation engineering"},{"issue":"2","key":"pcbi.1010556.ref120","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1088\/1741-2560\/5\/2\/008","article-title":"Computationally efficient models of neuromuscular recruitment and mechanics","volume":"5","author":"D Song","year":"2008","journal-title":"Journal of neural engineering"},{"issue":"14","key":"pcbi.1010556.ref121","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1016\/j.jbiomech.2016.08.030","article-title":"Dealing with time-varying recruitment and length in Hill-type muscle models","volume":"49","author":"A Hamouda","year":"2016","journal-title":"Journal of biomechanics"},{"issue":"11","key":"pcbi.1010556.ref122","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/0021-9290(96)84541-6","article-title":"Simulation of in situ soleus isometric force output as a function of neural excitation","volume":"29","author":"P Legreneur","year":"1996","journal-title":"Journal of biomechanics"},{"issue":"12","key":"pcbi.1010556.ref123","doi-asserted-by":"crossref","first-page":"e52618","DOI":"10.1371\/journal.pone.0052618","article-title":"EMG-Driven Forward-Dynamic Estimation of Muscle Force and Joint Moment about Multiple Degrees of Freedom in the Human Lower Extremity.","volume":"7","author":"M Sartori","year":"2012","journal-title":"PloS one."},{"issue":"14","key":"pcbi.1010556.ref124","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1016\/j.jbiomech.2015.09.021","article-title":"CEINMS: A toolbox to investigate the influence of different neural control solutions on the prediction of muscle excitation and joint moments during dynamic motor tasks","volume":"48","author":"C Pizzolato","year":"2015","journal-title":"Journal of Biomechanics"},{"key":"pcbi.1010556.ref125","first-page":"431","article-title":"Matching electrophysiological with morphological measurements in cat \u03b1-motoneurons","author":"JW Fleshman","year":"1983","journal-title":"Soc. 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