Leonardo Abdala Elias

Spinal Mechanisms May Provide a Combination of Intermittent and Continuous Control of Human Posture: Predictions from a Biologically Based Neuromusculoskeletal Model

Several models have been employed to study human postural control during upright quiet stance. Most have adopted an inverted pendulum approximation to the standing human and theoretical models to account for the neural feedback necessary to keep balance. The present study adds to the previous efforts in focusing more closely on modelling the physiological mechanisms of important elements associated with the control of human posture. This paper studies neuromuscular mechanisms behind upright stance control by means of a biologically based large-scale neuromusculoskeletal (NMS) model. It encompasses: i) conductance-based spinal neuron models (motor neurons and interneurons); ii) muscle proprioceptor models (spindle and Golgi tendon organ) providing sensory afferent feedback; iii) Hill-type muscle models of the leg plantar and dorsiflexors; and iv) an inverted pendulum model for the body biomechanics during upright stance. The motor neuron pools are driven by stochastic spike trains. Simulation results showed that the neuromechanical outputs generated by the NMS model resemble experimental data from subjects standing on a stable surface. Interesting findings were that: i) an intermittent pattern of muscle activation emerged from this posture control model for two of the leg muscles (Medial and Lateral Gastrocnemius); and ii) the Soleus muscle was mostly activated in a continuous manner. These results suggest that the spinal cord anatomy and neurophysiology (e.g., motor unit types, synaptic connectivities, ordered recruitment), along with the modulation of afferent activity, may account for the mixture of intermittent and continuous control that has been a subject of debate in recent studies on postural control. Another finding was the occurrence of the so-called “paradoxical” behaviour of muscle fibre lengths as a function of postural sway. The simulations confirmed previous conjectures that reciprocal inhibition is possibly contributing to this effect, but on the other hand showed that this effect may arise without any anticipatory neural control mechanism.

Models of passive and active dendrite motoneuron pools and their differences in muscle force control

Motoneuron (MN) dendrites may be changed from a passive to an active state by increasing the levels of spinal cord neuromodulators, which activate persistent inward currents (PICs). These exert a powerful influence on MN behavior and modify the motor control both in normal and pathological conditions. Motoneuronal PICs are believed to induce nonlinear phenomena such as the genesis of extra torque and torque hysteresis in response to percutaneous electrical stimulation or tendon vibration in humans. An existing large-scale neuromuscular simulator was expanded to include MN models that have a capability to change their dynamic behaviors depending on the neuromodulation level. The simulation results indicated that the variability (standard deviation) of a maintained force depended on the level of neuromodulatory activity. A force with lower variability was obtained when the motoneuronal network was under a strong influence of PICs, suggesting a functional role in postural and precision tasks. In an additional set of simulations when PICs were active in the dendrites of the MN models, the results successfully reproduced experimental results reported from humans. Extra torque was evoked by the self-sustained discharge of spinal MNs, whereas differences in recruitment and de-recruitment levels of the MNs were the main reason behind torque and electromyogram (EMG) hysteresis. Finally, simulations were also used to study the influence of inhibitory inputs on a MN pool that was under the effect of PICs. The results showed that inhibition was of great importance in the production of a phasic force, requiring a reduced co-contraction of agonist and antagonist muscles. These results show the richness of functionally relevant behaviors that can arise from a MN pool under the action of PICs.

Influences of premotoneuronal command statistics on the scaling of motor output variability during isometric plantar flexion

This study focuses on neuromuscular mechanisms behind ankle torque and EMG variability during a maintained isometric plantar flexion contraction. Experimentally obtained torque standard deviation (SD) and soleus, medial gastrocnemius, and lateral gastrocnemius EMG envelope mean and SD increased with mean torque for a wide range of torque levels. Computer simulations were performed on a biophysically-based neuromuscular model of the triceps surae consisting of premotoneuronal spike trains (the global input, GI) driving the motoneuron pools of the soleus, medial gastrocnemius, and lateral gastrocnemius muscles, which activate their respective muscle units. Two types of point processes were adopted to represent the statistics of the GI: Poisson and Gamma. Simulations showed a better agreement with experimental results when the GI was modeled by Gamma point processes having lower orders (higher variability) for higher target torques. At the same time, the simulations reproduced well the experimental data of EMG envelope mean and SD as a function of mean plantar flexion torque, for the three muscles. These results suggest that the experimentally found relations between torque-EMG variability as a function of mean plantar flexion torque level depend not only on the intrinsic properties of the motoneuron pools and the muscle units innervated, but also on the increasing variability of the premotoneuronal GI spike trains when their mean rates increase to command a higher plantar flexion torque level. The simulations also provided information on spike train statistics of several hundred motoneurons that compose the triceps surae, providing a wide picture of the associated mechanisms behind torque and EMG variability.

Experimental and Simulated EMG Responses in the Study of the Human Spinal Cord

Advances in the study of human spinal cord neurophysiology have been strongly based on the analysis of the electrical activity of muscles (electromyogram EMG). The EMG measured over the skin reflects the general behavior of motor units (MUs) and hence of spinal moto‐ neurons (MNs). It can be used, for instance, to infer changes in the behavior of neuronal circuits within the spinal cord during the performance of a motor task or in response to peripheral and/or descending inputs.

Individual and collective properties of computationally efficient motoneuron models of types S and F with active dendrites

The input-output properties of motoneurons (MNs) and motor units (MUs) may be modulated by different physiological variables, including neuromodulators released by presynaptic neurons from the brainstem. Monoamines, such as serotonin and norepinephrine, act on MNs mainly by activating dendritic L-type Ca^+^+ channels, generating a persistent inward current (PIC), which may change the input-output properties of the MU. If the firing properties of individual MNs and also the features of the force generated by the MUs can be changed, it follows that the descending monoaminergic systems may modulate the overall dynamics of motor control. The purpose of the present study is to investigate the effects of neuromodulation on the input-output properties of mathematically modeled type-specified MUs. Computationally efficient models are presented for S- and F-type mammalian MNs as well as a MN pool commanding muscle units of the Soleus muscle. The single models have a dendritic L-type Ca^+^+ channel, generating a PIC, along with somatic currents that are responsible for spike-generating mechanisms and the afterhyperpolarization. The S-type active-dendrite (AD) MN model resulted highly excitable and discharged in a self-sustained manner after an excitatory input (bistability). An inhibitory activity turned off this self-sustained discharge. In addition, this low-threshold MN model showed a significant reduction in interspike interval (ISI) variability in comparison with an equivalent passive-dendrite (PD) MN model discharging at a similar mean rate. The frequency response gain from presynaptic spike train rate modulation to output spike train modulation had a clear valley from about 1-10Hz for the S-type AD MN model, whereas the PD model showed a gain increase instead. On the other hand, the frequency responses of PD and AD F-type models were similarly shaped, with the AD model having a higher gain at high frequencies. These results suggest that in motor behaviors where steady or low frequency activity is required, such as posture, PICs would aid low-threshold MNs to respond with regular spikes, reducing output variability, and would attenuate the effects of high-frequency input disturbances, helping maintain system steadiness. At the same time, high-threshold MNs being more responsive to high-frequency disturbances would contribute with the necessary activity to correct for postural deviations from a desired position. Simulation results from the neuromuscular model have shown that the PIC activation profoundly affects muscle force generation, with the neuromodulatory activity acting in the adjustment of the motor output. Both individual and collective results presented here expand the understanding of the versatility of monoaminergic neuromodulation in adjusting both the MN input-output coding and the control of force generation.

Reassessment of non-monosynaptic excitation from the motor cortex to motoneurons in single motor units of the human biceps brachii

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.

Enhanced D1 and D2 Inhibitions Induced by Low-Frequency Trains of Conditioning Stimuli: Differential Effects on H- and T-Reflexes and Possible Mechanisms

Mechanically evoked reflexes have been postulated to be less sensitive to presynaptic inhibition (PSI) than the H-reflex. This has implications on investigations of spinal cord neurophysiology that are based on the T-reflex. Preceding studies have shown an enhanced effect of PSI on the H-reflex when a train of ~10 conditioning stimuli at 1 Hz was applied to the nerve of the antagonist muscle. The main questions to be addressed in the present study are if indeed T-reflexes are less sensitive to PSI and whether (and to what extent and by what possible mechanisms) the effect of low frequency conditioning, found previously for the H-reflex, can be reproduced on T-reflexes from the soleus muscle. We explored two different conditioning-to-test (C-T) intervals: 15 and 100 ms (corresponding to D1 and D2 inhibitions, respectively). Test stimuli consisted of either electrical pulses applied to the posterior tibial nerve to elicit H-reflexes or mechanical percussion to the Achilles tendon to elicit T-reflexes. The 1 Hz train of conditioning electrical stimuli delivered to the common peroneal nerve induced a stronger effect of PSI as compared to a single conditioning pulse, for both reflexes (T and H), regardless of C-T-intervals. Moreover, the conditioning train of pulses (with respect to a single conditioning pulse) was proportionally more effective for T-reflexes as compared to H-reflexes (irrespective of the C-T interval), which might be associated with the differential contingent of Ia afferents activated by mechanical and electrical test stimuli. A conceivable explanation for the enhanced PSI effect in response to a train of stimuli is the occurrence of homosynaptic depression at synapses on inhibitory interneurons interposed within the PSI pathway. The present results add to the discussion of the sensitivity of the stretch reflex pathway to PSI and its functional role.

Low-frequency fluctuations of plantar flexion torque in force and position control tasks studied experimentally and by a neuromusculoskeletal model

There are many feedback loops potentially active while a subject performs a plantar flexion. One of these loops encompasses the proprioceptive feedback from muscle spindle Ia afferents, motor neurons (MNs), and the muscle. The aim of this study was to investigate the role of the Ia feedback loop on the low-frequency fluctuations of the plantar flexion torque during the performance of a force task (FT) and a position task (PT). Experiments were conducted on healthy human subjects and provided reference data for computer simulations that were carried out on a biologically-based large-scale neuromusculoskeletal model. Spectral analysis was performed on both simulated and experimental torque (equivalent to 20% MV C). In addition, coherence analysis was performed on several simulated neuronal and biomechanical variables. The results suggest that Ia afferents are largely involved in the low-frequency fluctuations of plantar flexion torque.

D1 and D2 Inhibitions of the Soleus H-Reflex Are Differentially Modulated during Plantarflexion Force and Position Tasks

Presynaptic inhibition (PSI) has been shown to modulate several neuronal pathways of functional relevance by selectively gating the connections between sensory inputs and spinal motoneurons, thereby regulating the contribution of the stretch reflex circuitry to the ongoing motor activity. In this study, we investigated whether a differential regulation of Ia afferent inflow by PSI may be associated with the performance of two types of plantarflexion sensoriomotor tasks. The subjects (in a seated position) controlled either: 1) the force level exerted by the foot against a rigid restraint (force task, FT); or 2) the angular position of the ankle when sustaining inertial loads (position task, PT) that required the same level of muscle activation observed in FT. Subjects were instructed to maintain their force/position at target levels set at ~10% of maximum isometric voluntary contraction for FT and 90° for PT, while visual feedback of the corresponding force/position signals were provided. Unconditioned H-reflexes (i.e. control reflexes) and H-reflexes conditioned by electrical pulses applied to the common peroneal nerve with conditioning-to-test intervals of 21 ms and 100 ms (corresponding to D1 and D2 inhibitions, respectively) were evoked in a random fashion. A significant main effect for the type of the motor task (FT vs PT) (p = 0.005, η2 p = 0.603) indicated that PTs were undertaken with lower levels of Ia PSI converging onto the soleus motoneuron pool. Additionally, a significant interaction between the type of inhibition (D1 vs D2) and the type of motor task (FT vs PT) (p = 0.038, η2 p = 0.395) indicated that D1 inhibition was associated with a significant reduction in PSI levels from TF to TP (p = 0.001, η2 p = 0.731), whereas no significant difference between the tasks was observed for D2 inhibition (p = 0.078, η2 p = 0.305). These results suggest that D1 and D2 inhibitions of the soleus H-reflex are differentially modulated during the performance of plantarflexion FT and PT. The reduced level of ongoing PSI during PT suggests that, in comparison to FT, there is a larger reliance on inputs from muscle spindles primary afferents when the neuromuscular system is required to maintain position-controlled plantarflexion contractions.