Experimentally Valid Predictions of Muscle Force and EMG in Models of Motor-Unit Function Are Most Sensitive to Neural Properties

2007 ◽  
Vol 98 (3) ◽  
pp. 1581-1590 ◽  
Author(s):  
Kevin G. Keenan ◽  
Francisco J. Valero-Cuevas

Computational models of motor-unit populations are the objective implementations of the hypothesized mechanisms by which neural and muscle properties give rise to electromyograms (EMGs) and force. However, the variability/uncertainty of the parameters used in these models—and how they affect predictions—confounds assessing these hypothesized mechanisms. We perform a large-scale computational sensitivity analysis on the state-of-the-art computational model of surface EMG, force, and force variability by combining a comprehensive review of published experimental data with Monte Carlo simulations. To exhaustively explore model performance and robustness, we ran numerous iterative simulations each using a random set of values for nine commonly measured motor neuron and muscle parameters. Parameter values were sampled across their reported experimental ranges. Convergence after 439 simulations found that only 3 simulations met our two fitness criteria: approximating the well-established experimental relations for the scaling of EMG amplitude and force variability with mean force. An additional 424 simulations preferentially sampling the neighborhood of those 3 valid simulations converged to reveal 65 additional sets of parameter values for which the model predictions approximate the experimentally known relations. We find the model is not sensitive to muscle properties but very sensitive to several motor neuron properties—especially peak discharge rates and recruitment ranges. Therefore to advance our understanding of EMG and muscle force, it is critical to evaluate the hypothesized neural mechanisms as implemented in today's state-of-the-art models of motor unit function. We discuss experimental and analytical avenues to do so as well as new features that may be added in future implementations of motor-unit models to improve their experimental validity.

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Chengjun Huang ◽  
Maoqi Chen ◽  
Yingchun Zhang ◽  
Sheng Li ◽  
Ping Zhou

This study presents a model-based sensitivity analysis of the strength of voluntary muscle contraction with respect to different patterns of motor unit loss. A motor unit pool model was implemented including simulation of a motor neuron pool, muscle force, and surface electromyogram (EMG) signals. Three different patterns of motor unit loss were simulated, including (1) motor unit loss restricted to the largest ones, (2) motor unit loss restricted to the smallest ones, and (3) motor unit loss without size restriction. The model outputs including muscle force amplitude, variability, and the resultant EMG-force relation were quantified under two different motor neuron firing strategies. It was found that motor unit loss restricted to the largest ones had the most dominant impact on muscle strength and significantly changed the EMG-force relation, while loss restricted to the smallest motor units had a pronounced effect on force variability. These findings provide valuable insight toward our understanding of the neurophysiological mechanisms underlying experimental observations of muscle strength, force control, and EMG-force relation in both normal and pathological conditions.


2021 ◽  
Vol 376 (1821) ◽  
pp. 20190765 ◽  
Author(s):  
Giovanni Pezzulo ◽  
Joshua LaPalme ◽  
Fallon Durant ◽  
Michael Levin

Nervous systems’ computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states—in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits in vivo can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing in vivo . This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.


2004 ◽  
Vol 92 (2) ◽  
pp. 1175-1181 ◽  
Author(s):  
Dario I. Carrasco ◽  
Mark M. Rich ◽  
Qingbo Wang ◽  
Timothy C. Cope ◽  
Martin J. Pinter

The role of neuronal activity in the pathogenesis of neurodegenerative disease is largely unknown. In this study, we examined the effects of increasing motor neuron activity on the pathogenesis of a canine version of inherited motor neuron disease (hereditary canine spinal muscular atrophy). Activity of motor neurons innervating the ankle extensor muscle medial gastrocnemius (MG) was increased by denervating close synergist muscles. In affected animals, 4 wk of synergist denervation accelerated loss of motor-unit function relative to control muscles and decreased motor axon conduction velocities. Slowing of axon conduction was greatest in the most distal portions of motor axons. Morphological analysis of neuromuscular junctions (NMJs) showed that these functional changes were associated with increased loss of intact innervation and with the appearance of significant motor axon and motor terminal sprouting. These effects were not observed in the MG muscles of age-matched, normal animals with synergist denervation for 5 wk. The results indicate that motor neuron action potential activity is a major contributing factor to the loss of motor-unit function and degeneration in inherited canine motor neuron disease.


2021 ◽  
Vol 17 (3) ◽  
pp. e1008707
Author(s):  
Akira Nagamori ◽  
Christopher M. Laine ◽  
Gerald E. Loeb ◽  
Francisco J. Valero-Cuevas

Variability in muscle force is a hallmark of healthy and pathological human behavior. Predominant theories of sensorimotor control assume ‘motor noise’ leads to force variability and its ‘signal dependence’ (variability in muscle force whose amplitude increases with intensity of neural drive). Here, we demonstrate that the two proposed mechanisms for motor noise (i.e. the stochastic nature of motor unit discharge and unfused tetanic contraction) cannot account for the majority of force variability nor for its signal dependence. We do so by considering three previously underappreciated but physiologically important features of a population of motor units: 1) fusion of motor unit twitches, 2) coupling among motoneuron discharge rate, cross-bridge dynamics, and muscle mechanics, and 3) a series-elastic element to account for the aponeurosis and tendon. These results argue strongly against the idea that force variability and the resulting kinematic variability are generated primarily by ‘motor noise.’ Rather, they underscore the importance of variability arising from properties of control strategies embodied through distributed sensorimotor systems. As such, our study provides a critical path toward developing theories and models of sensorimotor control that provide a physiologically valid and clinically useful understanding of healthy and pathologic force variability.


2012 ◽  
Vol 107 (12) ◽  
pp. 3357-3369 ◽  
Author(s):  
Jakob L. Dideriksen ◽  
Francesco Negro ◽  
Roger M. Enoka ◽  
Dario Farina

Motoneurons receive synaptic inputs from tens of thousands of connections that cause membrane potential to fluctuate continuously (synaptic noise), which introduces variability in discharge times of action potentials. We hypothesized that the influence of synaptic noise on force steadiness during voluntary contractions is limited to low muscle forces. The hypothesis was examined with an analytical description of transduction of motor unit spike trains into muscle force, a computational model of motor unit recruitment and rate coding, and experimental analysis of interspike interval variability during steady contractions with the abductor digiti minimi muscle. Simulations varied contraction force, level of synaptic noise, size of motor unit population, recruitment range, twitch contraction times, and level of motor unit short-term synchronization. Consistent with the analytical derivations, simulations and experimental data showed that force variability at target forces above a threshold was primarily due to low-frequency oscillations in neural drive, whereas the influence of synaptic noise was almost completely attenuated by two low-pass filters, one related to convolution of motoneuron spike trains with motor unit twitches (temporal summation) and the other attributable to summation of single motor unit forces (spatial summation). The threshold force above which synaptic noise ceased to influence force steadiness depended on recruitment range, size of motor unit population, and muscle contractile properties. This threshold was low (<10% of maximal force) for typical values of these parameters. Results indicate that motor unit recruitment and muscle properties of a typical muscle are tuned to limit the influence of synaptic noise on force steadiness to low forces and that the inability to produce a constant force during stronger contractions is mainly attributable to the common low-frequency oscillations in motoneuron discharge rates.


2020 ◽  
Vol 27 ◽  
Author(s):  
Zaheer Ullah Khan ◽  
Dechang Pi

Background: S-sulfenylation (S-sulphenylation, or sulfenic acid) proteins, are special kinds of post-translation modification, which plays an important role in various physiological and pathological processes such as cytokine signaling, transcriptional regulation, and apoptosis. Despite these aforementioned significances, and by complementing existing wet methods, several computational models have been developed for sulfenylation cysteine sites prediction. However, the performance of these models was not satisfactory due to inefficient feature schemes, severe imbalance issues, and lack of an intelligent learning engine. Objective: In this study, our motivation is to establish a strong and novel computational predictor for discrimination of sulfenylation and non-sulfenylation sites. Methods: In this study, we report an innovative bioinformatics feature encoding tool, named DeepSSPred, in which, resulting encoded features is obtained via n-segmented hybrid feature, and then the resampling technique called synthetic minority oversampling was employed to cope with the severe imbalance issue between SC-sites (minority class) and non-SC sites (majority class). State of the art 2DConvolutional Neural Network was employed over rigorous 10-fold jackknife cross-validation technique for model validation and authentication. Results: Following the proposed framework, with a strong discrete presentation of feature space, machine learning engine, and unbiased presentation of the underline training data yielded into an excellent model that outperforms with all existing established studies. The proposed approach is 6% higher in terms of MCC from the first best. On an independent dataset, the existing first best study failed to provide sufficient details. The model obtained an increase of 7.5% in accuracy, 1.22% in Sn, 12.91% in Sp and 13.12% in MCC on the training data and12.13% of ACC, 27.25% in Sn, 2.25% in Sp, and 30.37% in MCC on an independent dataset in comparison with 2nd best method. These empirical analyses show the superlative performance of the proposed model over both training and Independent dataset in comparison with existing literature studies. Conclusion : In this research, we have developed a novel sequence-based automated predictor for SC-sites, called DeepSSPred. The empirical simulations outcomes with a training dataset and independent validation dataset have revealed the efficacy of the proposed theoretical model. The good performance of DeepSSPred is due to several reasons, such as novel discriminative feature encoding schemes, SMOTE technique, and careful construction of the prediction model through the tuned 2D-CNN classifier. We believe that our research work will provide a potential insight into a further prediction of S-sulfenylation characteristics and functionalities. Thus, we hope that our developed predictor will significantly helpful for large scale discrimination of unknown SC-sites in particular and designing new pharmaceutical drugs in general.


2018 ◽  
Vol 14 (12) ◽  
pp. 1915-1960 ◽  
Author(s):  
Rudolf Brázdil ◽  
Andrea Kiss ◽  
Jürg Luterbacher ◽  
David J. Nash ◽  
Ladislava Řezníčková

Abstract. The use of documentary evidence to investigate past climatic trends and events has become a recognised approach in recent decades. This contribution presents the state of the art in its application to droughts. The range of documentary evidence is very wide, including general annals, chronicles, memoirs and diaries kept by missionaries, travellers and those specifically interested in the weather; records kept by administrators tasked with keeping accounts and other financial and economic records; legal-administrative evidence; religious sources; letters; songs; newspapers and journals; pictographic evidence; chronograms; epigraphic evidence; early instrumental observations; society commentaries; and compilations and books. These are available from many parts of the world. This variety of documentary information is evaluated with respect to the reconstruction of hydroclimatic conditions (precipitation, drought frequency and drought indices). Documentary-based drought reconstructions are then addressed in terms of long-term spatio-temporal fluctuations, major drought events, relationships with external forcing and large-scale climate drivers, socio-economic impacts and human responses. Documentary-based drought series are also considered from the viewpoint of spatio-temporal variability for certain continents, and their employment together with hydroclimate reconstructions from other proxies (in particular tree rings) is discussed. Finally, conclusions are drawn, and challenges for the future use of documentary evidence in the study of droughts are presented.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rowan P. Rimington ◽  
Jacob W. Fleming ◽  
Andrew J. Capel ◽  
Patrick C. Wheeler ◽  
Mark P. Lewis

AbstractInvestigations of the human neuromuscular junction (NMJ) have predominately utilised experimental animals, model organisms, or monolayer cell cultures that fail to represent the physiological complexity of the synapse. Consequently, there remains a paucity of data regarding the development of the human NMJ and a lack of systems that enable investigation of the motor unit. This work addresses this need, providing the methodologies to bioengineer 3D models of the human motor unit. Spheroid culture of iPSC derived motor neuron progenitors augmented the transcription of OLIG2, ISLET1 and SMI32 motor neuron mRNAs ~ 400, ~ 150 and ~ 200-fold respectively compared to monolayer equivalents. Axon projections of adhered spheroids exceeded 1000 μm in monolayer, with transcription of SMI32 and VACHT mRNAs further enhanced by addition to 3D extracellular matrices in a type I collagen concentration dependent manner. Bioengineered skeletal muscles produced functional tetanic and twitch profiles, demonstrated increased acetylcholine receptor (AChR) clustering and transcription of MUSK and LRP4 mRNAs, indicating enhanced organisation of the post-synaptic membrane. The number of motor neuron spheroids, or motor pool, required to functionally innervate 3D muscle tissues was then determined, generating functional human NMJs that evidence pre- and post-synaptic membrane and motor nerve axon co-localisation. Spontaneous firing was significantly elevated in 3D motor units, confirmed to be driven by the motor nerve via antagonistic inhibition of the AChR. Functional analysis outlined decreased time to peak twitch and half relaxation times, indicating enhanced physiology of excitation contraction coupling in innervated motor units. Our findings provide the methods to maximise the maturity of both iPSC motor neurons and primary human skeletal muscle, utilising cell type specific extracellular matrices and developmental timelines to bioengineer the human motor unit for the study of neuromuscular junction physiology.


2021 ◽  
Vol 7 (3) ◽  
pp. 50
Author(s):  
Anselmo Ferreira ◽  
Ehsan Nowroozi ◽  
Mauro Barni

The possibility of carrying out a meaningful forensic analysis on printed and scanned images plays a major role in many applications. First of all, printed documents are often associated with criminal activities, such as terrorist plans, child pornography, and even fake packages. Additionally, printing and scanning can be used to hide the traces of image manipulation or the synthetic nature of images, since the artifacts commonly found in manipulated and synthetic images are gone after the images are printed and scanned. A problem hindering research in this area is the lack of large scale reference datasets to be used for algorithm development and benchmarking. Motivated by this issue, we present a new dataset composed of a large number of synthetic and natural printed face images. To highlight the difficulties associated with the analysis of the images of the dataset, we carried out an extensive set of experiments comparing several printer attribution methods. We also verified that state-of-the-art methods to distinguish natural and synthetic face images fail when applied to print and scanned images. We envision that the availability of the new dataset and the preliminary experiments we carried out will motivate and facilitate further research in this area.


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