Voluntary co-contraction of ankle muscles alters motor unit discharge characteristics and reduces estimates of persistent inward currents.

Motoneuronal persistent inward currents (PICs) are both facilitated by neuromodulatory inputs and highly sensitive to local inhibitory circuits (e.g., Ia reciprocal inhibition). Methods aimed to increase group Ia reciprocal inhibition from the antagonistic muscle have been successful in decreasing PICs, and the diffuse actions of neuromodulators released during activation of remote muscles have increased PICs. However, it remains unknown how motoneurons function in the presence of simultaneous excitatory and inhibitory commands. To probe this topic, we investigated motor unit (MU) discharge patterns and estimated PICs during voluntary co-contraction of ankle muscles, which simultaneously demands the contraction of agonist-antagonist pairs. Twenty young adults randomly performed triangular ramps (10s up and down) of both co-contraction (simultaneous dorsiflexion and plantarflexion) and isometric dorsiflexion to a peak of 30% of their maximum muscle activity from a maximal voluntary contraction. Motor unit spike trains were decomposed from high-density surface electromyography recorded over the tibialis anterior (TA) using blind source separation algorithms. Voluntary co-contraction altered motor unit discharge rate characteristics, decreasing estimates of PICs by 20% (4.47 pulses per second (pps) vs 5.57 pps during isometric dorsiflexion). These findings suggest that, during voluntary co-contraction, the inhibitory input from the antagonist muscle overcomes the additional excitatory and neuromodulatory drive that may occur due to the co-contraction of the antagonist muscle, which constrains PIC behavior.

Motor unit firing rate modulation is more impaired during flexion synergy-driven contractions of the biceps brachii in chronic stroke.

Following a hemiparetic stroke, individuals exhibit altered motor unit firing patterns during voluntary muscle contractions, including impairments in firing rate modulation and recruitment. These individuals also exhibit abnormal muscle coactivation through multi-joint synergies (e.g., flexion synergy). Here, we investigate whether motor unit firing activity during flexion synergy-driven contractions of the paretic biceps brachii differs from that of voluntary contractions and use these differences to predict changes in descending motor commands. To accomplish this, we characterized motor unit firing patterns of the biceps brachii in individuals with chronic hemiparetic stroke during voluntary isometric elbow flexion contractions in the paretic and non-paretic limbs, as well as during contractions driven by voluntary effort and by flexion synergy expression in the paretic limb. We observed significant reductions in motor unit firing rate modulation from the non-paretic to paretic limb (non-paretic - paretic: 0.14 pps/%MVT, 95% CI: [0.09 0.19]) that were further reduced during synergy-driven contractions (voluntary paretic - synergy driven: 0.19 pps/%MVT, 95% CI: [0.14 0.25]). Moreover, using recently developed metrics, we evaluated how a stroke-induced reliance on indirect motor pathways alters the inputs that motor units receive and revealed progressive increases in neuromodulatory and inhibitory drive to the motor pool in the paretic limb, with the changes greatest during synergy-driven contractions. These findings suggest that an interplay between heightened neuromodulatory drive and alterations in inhibitory command structure may account for the observed motor unit impairments, further illuminating underlying neural mechanisms involved in the flexion synergy and its impact on motor unit firing patterns post-stroke.

Estimates of persistent inward currents in lower limb motoneurons are larger in females than in males.

Noninvasive 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 participants in human and nonhuman animal physiology studies are male, and it is assumed that 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. 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 (10 s 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 estimates of PICs were predicted by the fixed effects of sex, muscle, and their interaction. Despite a lack of sex-differences in peak discharge rates across all muscles, estimates of PICs were larger [χ2(1) = 6.26, P = 0.012] in females [4.73 ± 0.242 pulses per second (pps)] than in 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.NEW & NOTEWORTHY Sex-related differences in motoneuron analyses have emerged with greater inclusion of female participants, however, mechanisms for these differences remain unclear. Estimates of persistent inward currents (i.e., ΔF) in motoneurons of the lower limb muscles were larger in females than in males. This suggests neuromodulatory drive, monoaminergic signaling, intrinsic motoneuron properties, and/or descending motor commands may differ between the sexes, which provides a potential mechanism underlying previously reported sex-related differences in motoneuron discharge patterns.

A geometric approach to quantifying the neuromodulatory effects of persistent inward currents on individual motor unit discharge patterns.

Objective.All motor commands flow through motoneurons, which entrain control of their innervated muscle fibers, forming a motor unit (MU). Owing to the high fidelity of action potentials within MUs, their discharge profiles detail the organization of ionotropic excitatory/inhibitory as well as metabotropic neuromodulatory commands to motoneurons. Neuromodulatory inputs (e.g. norepinephrine, serotonin) enhance motoneuron excitability and facilitate persistent inward currents (PICs). PICs introduce quantifiable properties in MU discharge profiles by augmenting depolarizing currents upon activation (i.e. PIC amplification) and facilitating discharge at lower levels of excitatory input than required for recruitment (i.e. PIC prolongation).Approach. Here, we introduce a novel geometric approach to estimate neuromodulatory and inhibitory contributions to MU discharge by exploiting discharge non-linearities introduced by PIC amplification during time-varying linear tasks. In specific, we quantify the deviation from linear discharge ('brace height') and the rate of change in discharge (i.e. acceleration slope, attenuation slope, angle). We further characterize these metrics on a simulated motoneuron pool with known excitatory, inhibitory, and neuromodulatory inputs and on human MUs (number of MUs; Tibialis Anterior: 1448, Medial Gastrocnemius: 2100, Soleus: 1062, First Dorsal Interosseus: 2296).Main results. In the simulated motor pool, we found brace height and attenuation slope to consistently indicate changes in neuromodulation and the pattern of inhibition (excitation-inhibition coupling), respectively, whereas the paired MU analysis (ΔF) was dependent on both neuromodulation and inhibition pattern. Furthermore, we provide estimates of these metrics in human MUs and show comparable variability in ΔFand brace height measures for MUs matched across multiple trials.Significance. Spanning both datasets, we found brace height quantification to provide an intuitive method for achieving graded estimates of neuromodulatory and inhibitory drive to individual MUs. This complements common techniques and provides an avenue for decoupling changes in the level of neuromodulatory and pattern of inhibitory motor commands.

A computational approach for generating continuous estimates of motor unit discharge rates and visualizing population discharge characteristics.

Objective. Successive improvements in high density surface electromyography and decomposition techniques have facilitated an increasing yield in decomposed motor unit (MU) spike times. Though these advancements enhance the generalizability of findings and promote the application of MU discharge characteristics to inform the neural control of motor output, limitations remain. Specifically, (1) common approaches for generating smooth estimates of MU discharge rates introduce artifacts in quantification, which may bias findings, and (2) discharge characteristics of large MU populations are often difficult to visualize.Approach. In the present study, we propose support vector regression (SVR) as an improved approach for generating smooth continuous estimates of discharge rate and compare the fit characteristics of SVR to traditionally used methods, including Hanning window filtering and polynomial regression. Furthermore, we introduce ensembles as a method to visualize the discharge characteristics of large MU populations. We define ensembles as the average discharge profile of a subpopulation of MUs, composed of a time normalized ensemble average of all units within this subpopulation. Analysis was conducted with MUs decomposed from the tibialis anterior (N= 2128), medial gastrocnemius (N= 2673), and soleus (N= 1190) during isometric plantarflexion and dorsiflexion contractions.Main result. Compared to traditional approaches, we found SVR to alleviate commonly observed inaccuracies and produce significantly less absolute fit error in the initial phase of MU discharge and throughout the entire duration of discharge. Additionally, we found the visualization of MU populations as ensembles to intuitively represent population discharge characteristics with appropriate accuracy for visualization.Significance. The results and methods outlined here provide an improved method for generating estimates of MU discharge rate with SVR and present a unique approach to visualizing MU populations with ensembles. In combination, the use of SVR and generation of ensembles represent an efficient method for rendering population discharge characteristics.

Early Gender Differences in Pain and Functional Recovery Following Thoracolumbar Spinal Arthrodesis.

BACKGROUND: To analyze gender differences regarding the recovery experience (pain, function, complications) after spinal arthrodesis surgery. METHODS: Pre-operative and post-operative gender-based differences in patient-reported outcomes for open posterior spinal arthrodesis at 6 weeks, 3 months, 6 months, and 1 year were studied, including age, comorbidities, body mass index (BMI), diagnosis, number of vertebrae fused, type of surgery, primary vs. revision surgery, and complications. Statistical analysis included the use of Student's t-test, Chi square, linear regression, Mann-Whitney U test, and Spearman's rho. RESULTS: Primary or revision posterior arthrodesis was performed on 1931 consecutive adults (1219 females, 712 males) for deformity and degenerative pathologies. At surgery, females were older than males (61.7 years vs. 59.7 years, p < 0.01), had slightly more comorbidities (1.75 vs. 1.5, p < 0.01), and were more likely to undergo deformity correction (38% vs. 22%, p < 0.01). Females described more pre-op pain (female VAS = 6.54 vs. male VAS = 6.41, p < 0.01) and lower pre-op function (female ODI = 49.73 vs. male ODI = 46.52, p < 0.01). By 3 months post-op, there was no significant gender difference in VAS or ODI scores. Similar pain and function scores between males and females continued through 6 months and 12 months. CONCLUSION: Although females have more pain and dysfunction before undergoing spinal surgery, the differences in these values do not reach the Minimum Clinically Important Difference (MCID). Post-operatively, there is no difference in pain and function scores among males and females at 3, 6, and 12 months.

Experimentally Modifiable Parameters and Their Relation to the Tonic Vibration Reflex in Chronic Hemiparetic Stroke.

The tonic vibration reflex (TVR), a reflexive muscle contraction resulting from muscle or tendon vibration, is a useful tool in assessing spinal motoneuron excitability, particularly in hyperexcitable conditions, such as in chronic hemiparetic stroke. The influence of experimental parameters, for example the type of vibratory stimulus and limb configuration, and their interactions on the TVR response in chronic stroke is unknown, yet this knowledge is crucial for designing experiments with reliable TVR responses. Therefore, we conducted a screening experiment of six potential driving factors affecting the TVR response, with a D-optimal split plot fractional design matrix consisting of thirty-two combinations for each of the four participants with chronic hemiparetic stroke. Our results suggest that pre-vibration muscle activation level, vibration frequency, and stimulus application force, are all significant contributors to the TVR response in chronic hemiparetic stroke, along with an interaction between elbow flexion angle and muscle activity level. This investigation highlights the sensitivity of the TVR response in chronic hemiparetic stroke and motivates future designed experiments in understanding this reflex as it relates to motoneuron excitability.