Identification of Motor Unit Twitch Properties in the Intact Human In Vivo

Restoring natural motor function in neurologically injured individuals is challenging, largely due to the lack of personalization in current neurorehabilitation technologies. Signal-driven neuro-musculoskeletal models may offer a novel paradigm for devising novel closed-loop rehabilitation strategies according to an individual's physiology. However, current modelling techniques are constrained to bipolar electromyography (EMG), thereby lacking the resolution necessary to extract the activity of individual motor units (MUs) in vivo. In this work, we decoded MU spike trains from high-density (HD)-EMG to obtain relevant neural properties across multiple isometric plantar-dorsiflexion tasks. Then, we sampled MU statistical distributions and used them to reproduce MU specific activation profiles. Results showed bimodal distributions which may correspond to slow and fast MU populations. The estimated activation profiles showed a high degree of similarity to the reference torque (R2>0.8) across the recorded muscles. This suggests that the estimation of MU twitch properties is a crucial step for the translation of neural information into muscle force.Clinical Relevance- This work has multiple implications for understanding the underlying mechanism of motor impairment and for developing closed-loop strategies for modulating alpha motor circuitries in neurologically injured individuals

Peculiarities of the Tail-Withdrawal Reflex Circuit in Aplysia: a Model Study

The circuit of the tail-withdrawal reflex in Aplysia opens up possibilities to construct model systems allowing researchers to effectively investigate simple forms of learning and memory. Using the Python interface of the NEURON software, we simulated this reflex circuit and studied various characteristics of the latter. The phenomenon of spike frequency adaptation (SFA) and the period-adding bifurcation of the minimum were found in sensory neurons, when the latter were stimulated by square-wave stimuli. In all neurons of the circuit, variation of the stimulus strength first increased and then decreased the number of spikes in a burst. In addition, with decreases in the number of stimulated sensory neurons, a subliminal firing other than that in an intact burst appeared at the outputs of interneurons and motor neuron. Moreover, the potentials produced in the motor neuron induced corresponding oscillations of the muscle fiber force, which was indicative of a procedure of excitement-contraction coupling in the tail part of Aplysia. Finally, upon alteration of the conductance of synapses between interneurons and motoneuron, the duration of long-lasting responses increased regularly, implying synaptic plasticityОрганізація нервової мережі відсмикування „хвоста” в аплізії дозволяє побудувати модельну систему, за допомогою якої можна ефективно досліджувати прості форми навчання та пам’яті. Використовуючи інтерфейс Python та програмний засіб NEURON, ми змоделювали даний рефлекс та дослідили декілька властивостей модельної мережі. Феномени адаптації частоти розряду (SFA) та біфуркації з доданням періоду при мінімумі частоти спостерігалися в сенсорних нейронах в умовах стимуляції прямокутними стимулами. В усіх нейронах мережі зміни сили стимуляції призводили спочатку до збільшення числа піків у пачках, а потім до його зменшення. Окрім того, при зменшенні кількості стимульованих сенсорних нейронів на виходах інтернейронів та моторного нейрона з’являлася підпорогова кайма, що відрізнялася від такої в інтактних пачок. Більш того, потенціали, продуковані моторним нейроном, індукували відповідні осциляції сили, розвинутої м’язовим волокном, що свідчило про сполучення процесів збудження/скорочення у хвостовій частині аплізії. Нарешті, при змінах провідності синапсів між інтернейронами та мотонейронами тривалість „довгих” імпульсних відповідей закономірно збільшувалася, що вказувало на прояви синаптичної пластичності

Perspectives on the modeling of the neuromusculoskeletal system to investigate the influence of neurodegenerative diseases on sensorimotor control

The understanding of the neurophysiological mechanisms underlying movement control can be much furthered using computational models of the neuromusculoskeletal system. Biologically based multi-scale neuromusculoskeletal models have a great potential to provide new theories and explanations related to mechanisms behind muscle force generation at the molecular, cellular, synaptic, and systems levels. Albeit some efforts have been made to investigate how neurodegenerative diseases alter the dynamics of individual elements of the neuromuscular system, such diseases have not been analyzed from a systems viewpoint using multi-scale models. This perspective article synthesizes what has been done in terms of multi-scale neuromuscular development and points to a few directions where such models could be extended so that they can be useful in the future to discover early predictors of neurodegenerative diseases, as well as to propose new quantitative clinical neurophysiology approaches to follow the course of improvements associated with different therapies (drugs or others). Therefore, this article will present how existing biologically based multi-scale models of the neuromusculoskeletal system could be expanded and adapted for clinical applications. It will point to mechanisms operating at different levels that would be relevant to be considered during model development, along with implications for interpreting experimental results from neurological patients342176186CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP409302/2016-3; 312442/2017-3; 303809/2016-72015/21819-32015/14917-9; 2017/11464-

Postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents:A simulation study

Postinhibitory excitation is a transient overshoot of a neuron’s baseline firing rate following an inhibitory stimulus and can be observed in vivo in human motoneurons. However, the biophysical origin of this phenomenon is still unknown and both reflex pathways and intrinsic motoneuron properties have been proposed. We hypothesized that postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents (h-currents). Using an electrical circuit model, we investigated how h-currents can modulate the postinhibitory response of motoneurons. Further, we analyzed the spike trains of human motor units from the tibialis anterior muscle during reciprocal inhibition. The simulations revealed that the activation of h-currents by an inhibitory postsynaptic potential can cause a short-term increase in a motoneuron’s firing probability. This result suggests that the neuron can be excited by an inhibitory stimulus. In detail, the modulation of the firing probability depends on the time delay between the inhibitory stimulus and the previous action potential. Further, the postinhibitory excitation’s strength correlates with the inhibitory stimulus’s amplitude and is negatively correlated with the baseline firing rate as well as the level of input noise. Hallmarks of h-current activity, as identified from the modeling study, were found in 50% of the human motor units that showed postinhibitory excitation. This study suggests that h-currents can facilitate postinhibitory excitation and act as a modulatory system to increase motoneuron excitability after a strong inhibition.</p

Divergent response of low‐ versus high‐threshold motor units to experimental muscle pain:dfferential motor unit behavior during pain

Key points: The neural strategies behind the control of force during muscle pain are not well understood as previous research has been limited in assessing pain responses only during low-force contractions. Here we compared, for the first time, the behaviour of motor units recruited at low and high forces in response to pain. The results showed that motor units activated at low forces were inhibited while those recruited at higher forces increased their activity in response to pain. When analysing lower- and higher-threshold motor unit behaviour at high forces we observed differential changes in discharge rate and recruitment threshold across the motor unit pool. These adjustments allow the exertion of high forces in acutely painful conditions but could eventually lead to greater fatigue and stress of the muscle tissue. Abstract: During low-force contractions, motor unit discharge rates decrease when muscle pain is induced by injecting nociceptive substances into the muscle. Despite this consistent observation, it is currently unknown how the central nervous system regulates motor unit behaviour in the presence of muscle pain at high forces. For this reason, we analysed the tibialis anterior motor unit behaviour at low and high forces. Surface EMG signals were recorded from 15 healthy participants (mean age (SD) 26 (3) years, six females) using a 64-electrode grid while performing isometric ankle dorsiflexion contractions at 20% and 70% of the maximum voluntary force (MVC). Signals were decomposed and the same motor units were tracked across painful (intramuscular hypertonic saline injection) and non-painful (baseline, isotonic saline, post-pain) contractions. At 20% MVC, discharge rates decreased significantly in the painful condition (baseline vs. pain: 12.7 (1.1) Hz to 11.5 (0.9) Hz, P < 0.001). Conversely, at 70% MVC, discharge rates increased significantly during pain (baseline vs. pain: 19.7 (2.8) Hz to 21.3 (3.5) Hz, p = 0.029) and recruitment thresholds decreased (baseline vs. pain: 59.0 (3.9) %MVC to 55.9 (3.2) %MVC, p = 0.02). These results show that there is a differential adjustment between low- and high-threshold motor units during painful conditions. An increase in excitatory drive to high-threshold motor units is likely required to compensate for the inhibitory influence of nociceptive afferent inputs on low-threshold motor units. These differential mechanisms allow the force output to be maintained during acute pain but this strategy could lead to increased muscle fatigue and symptom aggravation in the long term

Reassessment Of Non-monosynaptic Excitation From The Motor Cortex To Motoneurons In Single Motor Units Of The Human Biceps Brachii

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 +/- 1.4 ms) and CMS (2.0 +/- 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and that these interneurons might be equivalent to those identified in animal experiments.11Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) KAKENHI [25702033, 26560282, 23500617, 26120002]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2009/15802-0, 2013/10433-1, 2012/05304-5]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Amplitude cancellation influences the association between frequency components in the neural drive to muscle and the rectified EMG signal

The rectified surface EMG signal is commonly used as an estimator of the neural drive to muscles and therefore to infer sources of synaptic input to motor neurons. Loss of EMG amplitude due to the overlap of motor unit action potentials (amplitude cancellation), however, may distort the spectrum of the rectified EMG and thereby its correlation with the neural drive. In this study, we investigated the impact of amplitude cancelation on this correlation using analytical derivations and a computational model of motor neuron activity, force, and the EMG signal. First, we demonstrated analytically that an ideal rectified EMG signal without amplitude cancellation (EMGnc) is superior to the actual rectified EMG signal as estimator of the neural drive to muscle. This observation was confirmed by the simulations, as the average coefficient of determination (r2) between the neural drive in the 1–30 Hz band and EMGnc (0.59±0.08) was matched by the correlation between the rectified EMG and the neural drive only when the level of amplitude cancellation was low (60% (contraction levels >15% MVC). Moreover, the simulations showed that a stronger (i.e. more variable) neural drive implied a stronger correlation between the rectified EMG and the neural drive and that amplitude cancellation distorted this correlation mainly for low-frequency components (<5 Hz) of the neural drive. In conclusion, the results indicate that amplitude cancellation distorts the spectrum of the rectified EMG signal. This implies that valid use of the rectified EMG as an estimator of the neural drive requires low contraction levels and/or strong common synaptic input to the motor neurons

A functional model and simulation of spinal motor pools and intrafascicular recordings of motoneuron activity in peripheral nerve

abstract: Decoding motor intent from recorded neural signals is essential for the development of effective neural-controlled prostheses. To facilitate the development of online decoding algorithms we have developed a software platform to simulate neural motor signals recorded with peripheral nerve electrodes, such as longitudinal intrafascicular electrodes (LIFEs). The simulator uses stored motor intent signals to drive a pool of simulated motoneurons with various spike shapes, recruitment characteristics, and firing frequencies. Each electrode records a weighted sum of a subset of simulated motoneuron activity patterns. As designed, the simulator facilitates development of a suite of test scenarios that would not be possible with actual data sets because, unlike with actual recordings, in the simulator the individual contributions to the simulated composite recordings are known and can be methodically varied across a set of simulation runs. In this manner, the simulation tool is suitable for iterative development of real-time decoding algorithms prior to definitive evaluation in amputee subjects with implanted electrodes. The simulation tool was used to produce data sets that demonstrate its ability to capture some features of neural recordings that pose challenges for decoding algorithms