Biology subjects

Skarabot, J.

Publications and source records attributed to Skarabot, J..

9 recordsLinked to original sources

bioRxiv2026

The heterogeneity of age-related muscle atrophy of lower limb muscles

Age-related skeletal muscle atrophy differs between upper and lower body muscles and may also differ between lower limb muscles, but these muscle-specific patterns remain poorly characterised. We acquired axial 3T magnetic resonance images from sex-balanced samples of thirty young (24+/-4 years) and thirty older adults (73+/-4 years). Muscle volume of seventeen lower limb muscles/compartments was quantified using manual segmentation and expressed as absolute volume, relative to body mass, and as a percentage of total muscle volume. Absolute muscle volume was lower in older adults in 13 out of 17 muscles compared to young, with substantial heterogeneity in the effect sizes (d=0.01-3.36). Age group * muscle interaction contrasts revealed muscle-specific age-related differences in volume. Three of the quadriceps muscles demonstrated greater age-related atrophy compared to several other muscles (e.g. vastus lateralis differing from 14 of the other 16 muscles; d[≥]1.54). Conversely, the anterior and deep posterior compartments of the shank and biceps femoris short head showed significantly smaller age-related atrophy than several other muscles. These interaction effects were exacerbated when expressed in relative terms. Consequently, three of four shank compartments, gluteus maximus and adductor magnus represented a greater proportion of total muscle volume in older adults, whereas the vastus lateralis, vastus intermedius, rectus femoris, semitendinosus, gracilis, and iliopsoas contributed a smaller proportion in older adults. These findings highlight the variability in age-related leg muscle atrophy in a large mixed sex cohort, resulting in a redistribution of muscle volume in the lower limb.

physiology↗

bioRxiv2026

Reduction in Ia afferent input via ischaemia alters motor unit discharge characteristics and estimates of persistent inward currents

Persistent inward currents (PICs) govern motoneuron output and are influenced by diffuse neuromodulation and local inhibition. When large diameter afferent feedback is lost, as in some neurological conditions, PICs might additionally amplify and prolong synaptic inputs. Here, we examined whether reducing Ia afferent transmission via ischaemic nerve block alters PIC contribution to tibialis anterior (TA) motor unit (MU) discharge. Across two experiments 12 adults (5 female) performed triangular-shaped isometric dorsiflexion to 30% (Experiments 1 and 2) and 50% (Experiment 2) maximum voluntary force (MVF) at baseline, after a 20-minute rest (control), and during occlusion after inducing an ischaemic nerve block, confirmed by abolition of the soleus H-reflex. TA myoelectrical activity measured during contractions was decomposed into MU spike trains, and from smoothed MU discharges, discharge rate hysteresis ({Delta}F) and ascending non-linearity (brace height) were quantified. Results from Experiment 1 involving contractions matched to absolute force levels revealed increased peak discharge rate, {Delta}F, and brace height post-occlusion. However, {Delta}F normalised to maximal theoretical hysteresis did not change across time points. In Experiment 2, where MVF was reassessed at each timepoint and contractions were matched to relative force, peak discharge rate, normalised {Delta}F and brace height increased post-occlusion compared to pre-, across both contraction intensities. {Delta}F only increased post-occlusion at 50% MVF, with no changes at 30% MVF. These results show that ischaemic block of large-diameter axons, likely reducing reciprocal inhibition, increases PIC contribution to discharge rate modulation, highlighting the role of Ia afferent input in shaping motoneuron output in humans.

neuroscience↗

bioRxiv2026

Spinal Mechanisms in Post-Activation Potentiation: Facilitation of Presynaptic Inhibition Contrasts H-Reflex Amplitude Reduction

This study investigated the spinal neural mechanisms underlying post-activation potentiation in ten healthy young males (21.9 {+/-} 4.8 years). Participants performed a 10-second maximal isometric plantarflexion, after which we measured twitch torque and assessed spinal excitability using the soleus H-reflex, D1 presynaptic inhibition and heteronymous Ia facilitation (HF). High-density surface EMG was decomposed to track single motor unit responses. The conditioning contraction increased twitch torque by 12.2 Nm (p < 0.001) immediately and returning to baseline within nine minutes. This mechanical potentiation was accompanied by a 29% reduction in H-reflex amplitude (p < 0.001), which recovered within three minutes. Paradoxically, neurophysiological indices of presynaptic inhibition, D1 and HF were significantly increased (D1: p<0.017; HF: p<0.001), resulting in spinal facilitation. Single MU analysis revealed increased discharge probability, particularly in higher-threshold units indicating overall spinal facilitation. These results demonstrate that post-activation potentiation involves a complex dissociation: H-reflex pathway inhibition along with facilitation of presynaptic spinal mechanisms. This paradox can be explained by either post-activation depression (caused by depletion of neurotransmitter at the Ia-motoneuron synapse) or muscle thixotropy, a contraction history-dependent decrease in muscle spindle sensitivity, which reduces the efficacy of the Ia afferent volley independently of spinal inhibitory mechanisms. Our findings highlight a dissociation between spinal presynaptic facilitation and the decreased H-reflex, underscoring the need for future studies to explicitly test the roles of post-activation depression and muscle thixotropy during post-activation potentiation. New & NoteworthyThis study provides evidence that post-activation potentiation reduces the soleus H-reflex amplitude while concurrently facilitating presynaptic spinal mechanisms. By combining global EMG and single motor unit analyses extracted from high-density surface EMG, we reveal a dissociation between spinal disinhibition and reflex depression. These findings suggest that acute post-contraction reflex suppression might be mediated by mechanisms other than presynaptic inhibition, potentially involving post-activation depression spinal mechanisms or changes in muscle spindle sensitivity.

neuroscience↗

bioRxiv2025

Training-induced alterations in the modulation of human motoneuron discharge patterns with contraction force

Motoneurons adapt to both resistance and endurance training in reduced animal preparations, with adaptations seemingly more apparent in higher threshold neurons, but similar evidence in humans is lacking. Here, we compared the identified motor unit (MU) discharge patterns from decomposed electromyography signals acquired during triangular dorsiflexion contractions up to 70% of maximal voluntary force (MVF) between resistance-trained, endurance-trained, and untrained individuals (n=23 in each group). We then estimated intrinsic motoneuron properties and garnered insight about the proportion of excitatory, inhibitory, and neuromodulatory inputs contributing to motor commands across contraction intensities in each group. Participants also performed a task where a triangular contraction was superimposed onto a sustained one designed to challenge inhibitory control of dendritic persistent inward currents (PICs). Both trained groups demonstrated greater MU discharge rates with greater ascending discharge rate modulation during higher contraction forces ([≥]50% MVF), which were accompanied by more linear MU discharge patterns and greater post-acceleration attenuation slopes of the ascending discharge rates. No differences in discharge rate hysteresis or the discharge rate characteristics during the sombrero tasks between groups, suggesting no differences in neuromodulatory input. Conversely, resistance-compared to endurance-trained individuals exhibited greater acceleration slopes during lower contractions forces ([≤]50% MVF), indicating the possibility of enhanced initial activation of PICs. Collectively, the greater and more linear MU discharge patterns in the trained groups either suggests a more reciprocal (i.e., push-pull) excitation-inhibition coupling during higher contraction forces or enhanced excitatory synaptic input to the motor pool, which might underpin greater force production of trained individuals.

neuroscience↗

bioRxiv2024

Motor unit discharge properties of the vastii muscles and their modulation with contraction level depend on the knee-joint angle

This study examined the effect of the knee-joint angle on motor unit (MU) discharge properties of the vastii muscles and their modulation with contraction level. Twelve young adults performed unilateral isometric knee-extension contractions during three experimental sessions at either 25, 55, and 85{degrees} of knee flexion (full extension: 0{degrees}) in a randomised order. Each session involved maximal voluntary contractions (MVCs) followed by submaximal trapezoidal and triangular contractions at different levels relative to maximal voluntary torque (MVT). High-density surface electromyograms were recorded from vastus lateralis and medialis muscles and, subsequently, decomposed to obtain discharge timings of individual MUs. MVT was the greatest, whereas MU discharge rate (DR) during MVCs and submaximal contraction levels ([≥]30% MVT) was the lowest at the intermediate joint angle (55{degrees}). The highest DR during MVCs and high-level contractions (70% MVT), however, was at the most flexed knee position (85{degrees}), which was due to a greater DR increase 50-70% MVT compared to 25{degrees} and 55{degrees}. The onset-offset DR hysteresis ({Delta}F), an estimate of persistent inward current contribution to motoneuron discharge, decreased with knee flexion and increased with contraction level, whereas the degree of motoneuron input-output nonlinearity (brace height) did not vary with joint angle but decreased with contraction level. At 85{degrees}, {Delta}F increased more and brace height decreased less with contraction level compared to 25{degrees} and 55{degrees}. These findings indicate that vastii MU DR and its modulation with contraction level vary with knee-joint angle, which could be partly explained by the modulation of motoneuron intrinsic electrical properties. NEW & NOTEWORTHYThis study explored the relationship between motoneuron output to the vastii muscles at different knee-joint angles (quadriceps lengths) and isometric contraction levels. We showed that the motor unit discharge rate was lowest at the angle of the greatest absolute torque capacity, whereas the contraction-level-induced increases in discharge rate and motoneuron excitability were the greatest in the flexed position. These findings suggest that joint-angle-dependent adjustments in sensory feedback modulate motor control of the knee-extensor muscles.

physiology↗

bioRxiv2023

Motor unit discharge rate modulation during isometric contractions to failure is intensity and task dependent

The nature of neuromuscular decrements associated with contractions to task failure is known to dependent on task demands. Task-specificity of the associated adjustments in motor unit discharge rate (MUDR) behaviour, however, remains unclear. This study examined MUDR adjustments during different submaximal isometric knee-extension tasks to failure. Participants performed a sustained and an intermittent task at 20 and 50% of maximal voluntary torque (MVT), respectively (Experiment 1). High-density surface electromyography signals were recorded from vastus lateralis (VL) and medialis (VM) and decomposed into individual MU discharge timings, with the identified MUs tracked from recruitment to task failure. MUDR was quantified and normalised to intervals of 10% of contraction time (CT). MUDR of both muscles exhibited distinct modulation patterns in each task. During 20% MVT sustained task, MUDR decreased until [~]50% CT, after which it gradually returned to baseline. Conversely, during the 50% MVT intermittent task, MUDR remained stable until [~]40-50% CT, after which it started to continually increase until task failure. To explore the effect of contraction intensity on the observed patterns, VL and VM MUDR was quantified during sustained contractions at 30 and 50% MVT (Experiment 2). During the 30% MVT sustained task, MUDR remained stable until [~]80-90% CT in both muscles, after which it continually increased until task failure. During the 50% MVT sustained task the increase in MUDR occurred earlier, after [~]70-80% CT. Our results suggest that adjustments in MUDR during submaximal isometric contractions to failure are task- and intensity-dependent.

neuroscience↗

bioRxiv2023

Human motor unit discharge patterns reveal differences in neuromodulatory and inhibitory drive to motoneurons across contraction levels

All motor commands converge onto motor units (MUs), which transduce the signals into mechanical actions of muscle fibres. This process is highly non-linear due to combinations of ionotropic (excitatory/inhibitory) and metabotropic (neuromodulatory) inputs. Neuromodulatory inputs facilitate dendritic persistent inward currents, which introduce non-linearities in MU discharge patterns and provide insights into the structure of motor commands. Here, we investigated the relative contribution of neuromodulation and the pattern of inhibition to modulate human MU discharge patterns with contraction forces up to 70% maximum. Leveraging MU discharge patterns identified from three human muscles (tibialis anterior - TA, and vastus lateralis and medialis), we show that with increased contraction force, the onset-offset discharge rate hysteresis ({Delta}F) increased whilst ascending MU discharge patterns become more linear, with lower slopes. In a follow-up experiment, we demonstrated that the observations of increased {Delta}F and more linear ascending MU discharge patterns with greater contraction force are maintained even when accounting for contraction duration and rate of force increase. We then reverse-engineered TA MU discharge patterns using highly realistic in silico motoneuron pools to substantiate the inferred physiological mechanisms from human recordings. We demonstrate a sharply restricted solution space, whereby the contraction force-induced changes in experimentally obtained MU discharge patterns can only be recreated with increased neuromodulation and a more reciprocal (i.e. push-pull) inhibitory pattern. In summary, our experimental and computational data suggest that neuromodulation and inhibitory patterns are uniquely shaped to generate discharge patterns that support force increases across a large proportion of the motor pools recruitment range. Significance statementHow the structure of motor commands is modified to scale motor output is largely speculative despite its critical role in the neural control of movement. Here, we demonstrate that human motor unit discharge patterns become more linear and exhibit greater discharge rate hysteresis with greater contraction force. These experimentally observed patterns can only be replicated in silico with biophysical models of spinal motoneurons by increasing neuromodulation and shifting inhibitory commands to be more reciprocal to excitation (i.e., push-pull excitation-inhibition synaptic control). Collectively, these results suggest that the structure of motor commands is uniquely orchestrated to support increases in contraction force.

neuroscience↗

bioRxiv2023

Reduced motoneuron excitability and common synaptic inputs of the aged human vastus lateralis

Although muscle atrophy may partially account for age-related strength decline, it is further influenced by alterations of neural input to muscle. Persistent inward currents and the level of common synaptic inputs to motoneurons influence neuromuscular function. However, these have not yet been described in aged human quadriceps. High density surface electromyography (HDsEMG) signals were collected from the vastus lateralis of 15 young (mean{+/-}SD, 23 {+/-} 5 y) and 15 older (67 {+/-} 9 y) men during submaximal sustained and 20-s ramped contractions. HDsEMG signals were decomposed to identify individual motor unit discharges, from which delta F and intramuscular coherence were estimated. Older participants produced significantly lower knee extensor torque (p<0.001) and poorer force tracking ability (p<0.001) than young. Older participants also had lower delta F (p=0.001) and coherence estimates in the alpha frequency band (p<0.001) during ramp contractions when compared to young. Persistent inward currents and common synaptic inputs are lower in the vastus lateralis of older males when compared to young. These data highlight altered neural input to the clinically and functionally important quadriceps, further underpinning age-related loss of function which may occur independently of the loss of muscle mass. Key PointsO_LIThe age-related loss of muscle mass is exceeded by the loss of function, which is influenced by structural and functional alterations of the nervous system. C_LIO_LIMotoneuronal persistent inward currents and common synaptic inputs play an important role in the activation of motor units and subsequent force generation and control ability. C_LIO_LIHere we show reduced estimates of persistent inward currents and lower common synaptic inputs to older vastus lateralis, potentially contributing to observed lower strength and poorer force tracking. C_LIO_LIThese findings highlight decrements of the aged human motor system, accompanied by muscle atrophy in functionally relevant muscle groups, which should be considered in the application of interventions targeting aged human muscle. C_LI

physiology↗

bioRxiv2022

Reticulospinal drive increases maximal motoneuron output in humans

Maximal rate of force development in adult humans is determined by the maximal motoneuron output, however the origin of the underlying synaptic inputs remains unclear. Here, we tested a hypothesis that the maximal motoneuron output will increase in response to a startling cue, a stimulus that purportedly activates the pontomedullary reticular formation neurons that make mono- and disynaptic connections to motoneurons via fast-conducting axons. Twenty-two men were required to produce isometric knee extensor forces "as fast and as hard" as possible from rest to 75% of maximal voluntary force, in response to visual (VC), visual-auditory (VAC), or visual-startling cue (VSC). Motoneuron activity was estimated via decomposition of high-density surface electromyogram recordings over the vastus lateralis and medialis muscles. Reaction time was significantly shorter in response to VSC compared to VAC and VC (i.e., the StartReact effect). The VSC further elicited faster neuromechanical responses including a greater number of discharges per motor unit per second and greater maximal rate of force development, with no differences between VAC and VC. We provide evidence, for the first time, that the synaptic input to motoneurons increases in response to a startling cue, suggesting a contribution of subcortical pathways to maximal motoneuron output in humans, likely originating from the pontomedullary reticular formation.

physiology↗