Biology subjects

Negro, F.

Publications and source records attributed to Negro, F..

28 records · Page 2Linked to original sources

bioRxiv2023

Adaptive HD-sEMG decomposition: Towards robust real-time decoding of neural drive

Neural interfacing via decomposition of high-density surface electromyography (HD-sEMG) should be robust to signal non-stationarities incurred by changes in joint pose and contraction intensity. We present an adaptive real-time motor unit (MU) decoding algorithm and test it on HD-sEMG collected from the extensor carpi radialis brevis during isometric contractions over a range of wrist angles and contraction intensities. The performance of the algorithm was verified using high-confidence benchmark decompositions derived from concurrently recorded intramuscular electromyography (iEMG). In trials where contraction conditions between the initialization and testing data differed, the adaptive decoding algorithm maintained significantly higher decoding accuracies when compared to static decoding methods. Using gold standard verification techniques, we demonstrate the limitations of filter re-use decoding methods and show the necessity of parameter adaptation to achieve robust neural decoding.

neuroscience↗

bioRxiv2023

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

Postinhibitory excitation is a transient overshoot of a neurons 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 motoneurons 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 strength of the postinhibitory excitation correlates with the amplitude of the inhibitory stimulus 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. Author SummaryHuman movement is determined by the activity of specialized nerve cells, the motoneurons. Each motoneuron activates a specific set of muscle fibers. The functional unit consisting of a neuron and muscle fibers is called a motor unit. The activity of motoneurons can be observed noninvasively in living humans by recording the electrical activity of the motor units using the electromyogram. We studied the behavior of human motor units in an inhibitory reflex pathway and found an unexpected response pattern: a rebound-like excitation following the inhibition. This has occasionally been reported for human motor units, but its origin has never been systematically studied. In non-human cells of the neural system, earlier studies reported that a specific membrane protein, the so-called h-channel, can cause postinhibitory excitation. In our study, we use a computational motoneuron model to investigate whether h-channels can cause postinhibitory excitation as observed in the experimental recordings. Using the model, we developed a method to detect features of h-channel activity in human recordings. Because we found these features in a half of the recorded motor units, we conclude that h-channels can facilitate postinhibitory excitation in human motoneurons.

neuroscience↗

bioRxiv2023

The short-term acquisition of a skill learning task unveils the neural filtering of shared synaptic input to spinal motor neurons

The acquisition of a motor skill involves adaptations of spinal and supraspinal pathways to alpha motoneurons. In this study, we estimated the shared synaptic contributions of these pathways to understand the neural mechanisms underlying the short-term acquisition of a new force-matching task. High-density surface electromyography (HDsEMG) was acquired from the first dorsal interosseous (FDI; 7 males and 6 females) and tibialis anterior (TA; 7 males and 4 females) during 15 trials of an isometric force-matching task. For two selected trials (pre- and post-skill acquisition), we decomposed the HDsEMG into motor unit spike trains, tracked motor units between trials, and calculated the mean discharge rate and the coefficient of variation of inter-spike interval (CoVISI). We also quantified the post/pre ratio of motor units coherence within delta, alpha, and beta bands. Improvements in force-matching were accompanied by a significant increase in the mean discharge rate and a decrease in CoVISI for both muscles. Moreover, the area under the curve within alpha band decreased by [~]22% and [~]13% for the TA and FDI muscles, respectively, with no changes in the delta or beta bands. These reductions correlated significantly with increased coupling between force/neural drive and target oscillations. These results suggest that the short-term acquisition of a new force-matching skill is mediated by the attenuation of tremor oscillations in the shared synaptic inputs. In other words, the central nervous system acts as a matched filter to modulate the synaptic weights of shared inputs and suppress neural components unrelated to the specific task. Supported by simulations, a plausible mechanism behind these alpha band reductions may involve spinal interneurons phase-cancelling descending oscillations.

neuroscience↗

bioRxiv2022

The effects of biological sex on estimates of persistent inward currents in the human lower limb

Non-invasive recordings of motor unit (MU) spike trains help us understand how the nervous system controls movement and how it adapts to various physiological conditions. The majority of study participants in human and non-human animal physiology studies are male, and it is assumed mechanisms uncovered in these studies are shared between males and females. However, sex differences in neurological impairment and physical performance warrant the study of sex as a biological variable in human physiology and performance. To begin addressing this gap in the study of biophysical properties of human motoneurons, we quantified MU discharge rates and estimates of persistent inward current (PIC) magnitude in both sexes by quantifying {Delta}F. We decomposed MU spike trains from the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SOL) using high-density surface electromyography and blind source separation algorithms. Ten participants of each sex performed slow triangular (10s up and down) isometric contractions to a peak of 30% of their maximum voluntary contraction. We then used linear mixed effects models to determine if peak discharge rate and {Delta}F were predicted by the fixed effects of sex, muscle, and their interaction. Despite a lack of significant sex-differences in peak discharge rates across all muscles, {Delta}F was larger ({chi}2(1) = 6.26, p = 0.012) in females (4.73 {+/-} 0.242 pps) than males (3.81 {+/-} 0.240 pps). These findings suggest that neuromodulatory drive, inhibitory input, and/or biophysical properties of motoneurons differ between the sexes and may contribute to differences in MU discharge patterns. KEY POINTS- Sex differences in motor unit studies have been revealed with greater inclusion of female participants, however, mechanisms for these differences remain unclear. - Estimates of persistent inward currents (i.e., {Delta}F) were greater in females than males in the tibialis anterior, medial gastrocnemius, and soleus muscles. - This suggests that neuromodulatory drive, monoaminergic signaling, or descending control may differ between the sexes. - Therefore, sex differences in estimates of PICs may provide a mechanism behind previously reported sex differences in motoneuron discharge patterns..

neuroscience↗

bioRxiv2022

Antagonist tendon vibration dampens estimates of persistent inward currents in motor units of the human lower limb

We can readily measure motoneuron discharge patterns in humans due to the one-to-one spike relation between motoneuron and muscle fiber action potentials, which allows us to make inferences about motor commands. Persistent inward currents (PICs), which provide gain control of motoneuronal output, are facilitated by monoaminergic input from the brainstem. This monoaminergic input is greatly diffuse, but resulting PICs are highly sensitive to inhibitory inputs. Antagonist muscle stretch, and thus Ia input from the antagonist decreases PIC magnitudes in the decerebrate cat. In the present study, we explored whether estimates of PICs are altered with vibratory input to antagonist muscles in humans. MUs of the tibialis anterior (TA), soleus (SOL), and medial gastrocnemius (MG) were discriminated using high-density surface electromyography and convolutive blind source separation. We estimated PICs using the paired MU analysis technique, which quantifies discharge rate hysteresis ({Delta}F) by comparing the discharge rate of a lower-threshold MU at the onset and offset of a higher-threshold MU. Participants performed isometric plantarflexion and dorsiflexion contractions to a peak of 30% of maximal voluntary contraction, with 10 s ascending and descending phases. In half of the trials, we applied vibration to the antagonist tendon and found that {Delta}F in agonist MUs decreased in the presence of vibration. These findings suggest that inhibition from the antagonist muscle, most likely Ia reciprocal inhibition, can reduce discharge rate hysteresis. This provides insights about non-invasive methods potentially capable of dampening PICs in hyperexcitable motoneurons, which are manifest in some neurological impairments. KEY POINTSO_LIPersistent inward currents in motoneurons amplify synaptic inputs and thus have a major impact on motor unit firing patterns. C_LIO_LIWe show that sustained vibration to the antagonist tendon reduces estimates of persistent inward currents ({Delta}F) of the contracting muscle in both the plantarflexors and dorsiflexors. C_LIO_LIThese findings provide evidence for the important role of sensory input in the control of persistent inward currents in the human. C_LIO_LIReciprocal inhibition may help refine neuromodulatory commands to tailor motor unit activation to diverse movement patterns and specific tasks, and loss of inhibition may exacerbate symptoms of neurological impairment. C_LI

physiology↗

bioRxiv2022

Orphan nuclear receptors Err2 and 3 promote a feature-specific terminal differentiationprogram underlying gamma motor neuron function and proprioceptive movement control

Motor neurons are commonly thought of as mere relays between the central nervous system and the movement apparatus, yet, in mammals about one-third of them function exclusively as regulators of muscle proprioception. How these gamma motor neurons acquire properties to function differently from the muscle force-producing alpha motor neurons remains unclear. Here, we found that upon selective loss of the orphan nuclear receptors Err2 and Err3 (Err2/3) in mice, gamma motor neurons acquire characteristic structural (e.g. synaptic wiring), but not functional (e.g. physiological firing rates) properties necessary for regulating muscle proprioception, thus disrupting gait and precision movements in vivo. Moreover, Err2/3 operate via transcriptional activation of neural activity modulators, one of which (Kcna10) promoted gamma motor neuron functional properties. Our work identifies a long-sought mechanism specifying gamma motor neuron properties necessary for proprioceptive movement control, which implies a feature-specific terminal differentiation program implementing neuron subtype-specific functional but not structural properties. SummaryThe transcription factors Err2 and 3 promote functional properties in a subset of motor neurons necessary for executing precise movements.

neuroscience↗

bioRxiv2021

Estimates of persistent inward currents are reduced in upper limb motor units of older adults

Aging is a natural process that causes alterations in the neuromuscular system, which contribute to weakness and reduced quality of life. Reduced firing rates of individual motor units (MUs) likely contribute to weakness, but the mechanisms underlying reduced firing rates are not clear. Persistent inward currents (PICs) are crucial for the initiation, gain control, and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since the concentration of monoamines (i.e. serotonin and norepinephrine) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to younger adults (<35 years old). We decomposed MU spike trains from high-density surface electromyography over the biceps brachii and triceps brachii during isometric ramp contractions to 20% of maximum. Estimates of PICs (i.e. {Delta}F) were computed using the paired MU analysis technique. Regardless of the muscle, peak firing rates of older adults were reduced by ~1.6 pulses per second (pps) (P = 0.0292), and {Delta}F was reduced by ~1.9 pps (P < 0.0001), compared to younger adults. We further found that age predicted {Delta}F in older adults (P = 0.0261), resulting in a reduction of ~1pps per decade, but there was no relationship in younger adults (P = 0.9637). These findings suggest that PICs are reduced in older adults, and, further, age is a significant predictor of estimates of PICs in older adults. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and weakness in older individuals. KEY POINTSO_LIPersistent inward currents play an important role in the neural control of human movement and are influenced by neuromodulation via monoamines originating in the brainstem. C_LIO_LIDuring aging, motor unit firing rates are reduced, and there is deterioration of brainstem nuclei, which may reduce persistent inward currents in alpha motoneurons. C_LIO_LIHere we show that estimates of persistent inward currents ({Delta}F) of both elbow flexor and extensor motor units are reduced in older adults. C_LIO_LIEstimates of persistent inward currents have a negative relationship with age in the older adults, but not young. C_LIO_LIThis novel mechanism may play a role in alteration motor firing rates that occurs with aging, which may have consequences for motor control. C_LI

physiology↗

bioRxiv2021

Concurrent assessment of motor unit firing properties and fascicle length changes with high-density surface electromyography ultrasound-transparent electrodes

The integration of electromyography (EMG) and ultrasound imaging has provided important information about the mechanisms of muscle activation and contraction. Unfortunately, EMG does not allow an accurate assessment of the interplay between the neural drive received by muscles, changes in fascicle length (FL) and the force/torque produced. We aimed to assess the relationship between modulations in tibialis anterior (TA) motor unit (MU) firing rate, FL and dorsiflexion torque (DT) using ultrasound-transparent high-density EMG electrodes. EMG and ultrasound images were recorded simultaneously from TA, using a 32-electrode silicon matrix, while performing isometric dorsiflexion, at diverse ankle joint positions (0{degrees} and 30{degrees} plantar flexion) and torques (20% and 40% of maximum). EMG signals were decomposed into individual MUs and changes in FL were assessed with a fascicle-tracking algorithm. MU firings were converted into a cumulative spike train (CST) that was cross-correlated with DT (CST-DT) and FL (CST-FL). High cross-correlations were found for CST-FL, 0.60 (range: 0.31-0.85) and CST-DT 0.71 (range: 0.31-0.88). Cross-correlation lags revealed that the delay between CST-FL (~75ms) was significantly smaller than CST-DT (~150ms, p<0.001). These delays affected the interpretation of MU recruitment/de-recruitment thresholds, with FL showing similar lengths for both recruitment and de-recruitment. This study is the first to demonstrate that changes in TA FL are closely related to both modulations in MU firing frequency and DT. These relationships allow assessment of the interplay between neural drive, muscle contraction and resultant torque, thereby providing a better understanding of the mechanisms responsible for the generation of muscle force. NEW AND NOTEWORTHYBy employing ultrasound-transparent high-density surface EMG electrodes, we show that modulations in tibialis anterior motor unit discharge rate were closely related to both changes in its fascicle length and resultant torque. These relationships allowed quantifying delays between neural drive and muscle shortening as well as muscle shortening and torque during submaximal isometric contractions, providing an accurate estimation of the time required to generate muscle force and subsequent production of torque via the tendon.

physiology↗

bioRxiv2021

Facilitation of sensory axon conduction to motoneurons during cortical or sensory evoked primary afferent depolarization (PAD) in humans

Sensory and corticospinal (CST) pathways activate spinal GABAergic interneurons with axo-axonic connections onto proprioceptive (Ia) afferents that depolarize these afferents (termed primary afferent depolarization, PAD). In rodents sensory-evoked PAD is produced by GABAA receptors at nodes of Ranvier in Ia-afferents, rather than at presynaptic terminals, and facilitates action potential propagation to motoneurons by preventing branch point failures, rather than causing presynaptic inhibition. Here we examined if PAD likewise facilitates the Ia-afferent mediated H-reflex in humans by evoking PAD with both sensory and CST stimulation. H-reflexes in several lower limb muscles were facilitated by prior conditioning from low-threshold proprioceptive, cutaneous or CST pathways, with a similar time course ([~]200 ms) to the PAD measured in rodent Ia-afferents. Long trains of repeated cutaneous or proprioceptive afferent stimulation produced long-lasting facilitation of the H-reflex for up to 2 minutes, consistent with the tonic depolarization of rodent Ia-afferents mediated by nodal 5-GABA receptors for similar stimulation trains. Facilitation of the conditioned H-reflexes was not mediated by direct facilitation of the motoneurons because isolated stimulation of sensory or CST pathways did not modulate the firing rate of tonically activated motor units in tested muscles. Furthermore, cutaneous conditioning increased the firing probability of a single motor unit during the H-reflex without increasing its firing rate at this time, indicating that the underlying excitatory postsynaptic potential (EPSP) was more probable, but not larger. These results are consistent with sensory and CST pathways activating nodal GABAA receptors that reduce intermittent failure of action potentials propagating into Ia-afferent branches. Key Points SummaryO_LIThe control of posture and movement requires peripheral sensory feedback, which was previously thought to be inhibited by specialized GABAergic neurons in the spinal cord. C_LIO_LIBased on new findings in rodents, we provide evidence in humans that sensory and corticospinal pathways that likely activate these GABAergic pathways facilitate, rather than inhibit, the flow of sensory feedback in afferents that carry information about body position, movement and effort. C_LIO_LIThese new findings of how sensory and descending pathways facilitate this sensory feedback to spinal motor neurons can now be applied to people with injury to the brain or spinal cord where these GABA neurons are affected, allowing us to understand how altered sensory control may affect residual motor function and the production of involuntary muscle spasticity. C_LI

neuroscience↗

bioRxiv2019

Sensitivity of the paired motor unit analysis for estimation of motoneuron excitability to commonly used constraints and filters

The nervous system has a tremendous ability to modify motoneuron excitability according to task demands through neuromodulatory synaptic input to motoneurons. Neuromodulatory inputs adjust the response of the motoneuron to excitatory and inhibitory ionotropic input and can facilitate the induction of persistent inward currents (PICs). PICs amplify and prolong the motoneuron response to synaptic inputs, and PIC impairment may play a major role in motor deficits observed in pathological conditions. Noninvasive estimation of the magnitude of neuromodulatory input and persistent inward currents in human motoneurons is achieved through a paired motor unit analysis ({Delta}F) that quantifies hysteresis in the firing rates at motor unit recruitment and derecruitment. While the {Delta}F technique is commonly used for estimating motoneuron excitability, computational parameters used for the technique vary across studies. In the present study, we assessed the sensitivity of the {Delta}F technique to several criteria commonly used in selecting motor unit pairs for analysis, as well as to methods used for smoothing the instantaneous motor unit firing rates. Using HD-sEMG and motor unit decomposition we obtained 5,409 motor unit pairs from the triceps brachii of ten healthy individuals during submaximal triangle contractions. The mean (SD) {Delta}F was 4.9 (1.08) pps, consistent with previous work using intramuscular recordings. There was an exponential plateau relationship between {Delta}F and the recruitment time difference between the motor unit pairs, with the plateau occurring at approximately 1 s. There was an exponential decay relationship between {Delta}F and the derecruitment time difference between the motor unit pairs, with the decay stabilizing at approximately 1.5 s. We found that reducing or removing the minimum threshold for the correlation of the rate-rate slope for the two units did not affect {Delta}F values or variance. Additionally, we found that removing motor unit pairs in which the control unit was saturated had no significant effect on {Delta}F. Smoothing filter selection had no substantial effect on {Delta}F values and {Delta}F variance; however, the length and type of smoothing filter affected the minimum recruitment and derecruitment time differences. Our results facilitate interpretation of findings from studies that implement the {Delta}F approach but use different computational parameters.

neuroscience↗