Biology subjects

Holobar, A.

Publications and source records attributed to Holobar, A..

8 recordsLinked to original sources

bioRxiv2026

Dopaminergic Medication Improves Force Control and Modifies Motor Unit Activity During the Steadiest and Least Steady Periods in Parkinsons Disease

Parkinsons disease (PD) impairs steady force production, but how dopaminergic medication alters force control and the motor unit (MU) activity is unclear. This study examined force steadiness and biceps brachii MU behavior in 16 people with PD ON and OFF dopaminergic medication. Participants performed sustained isometric elbow flexion contractions at 5%, 10%, 15%, and 25% of maximum voluntary contraction (MVC). High density surface electromyography was decomposed into MU spike trains. Force steadiness and MU discharge properties were quantified during nonoverlapping 7-s steadiest and least steady contraction periods, whereas MU coherence was assessed across the force plateau. In the ON state, force steadiness improved by 17_19% during both contraction periods at 5_15% MVC. MU interspike interval variability decreased by [~]12% across all forces during the least steady contraction period and by 17% at 15% MVC during the steadiest contraction period, whereas mean MU discharge rate was unchanged. Recruitment thresholds were higher at 10% and 25% MVC in the ON state, whereas derecruitment thresholds did not differ. Across the entire plateau, alpha- and tremor-band MU coherence decreased by 14% and 18%, respectively, whereas delta-band coherence was unchanged. These findings demonstrate that dopaminergic medication improves both the steadiest and least steady periods of low-force control, accompanied by reduced MU discharge variability and frequency-specific changes in plateau-wide MU coherence rather than changes in mean discharge rate. Resolving within-contraction variation reveals medication-sensitive features of force control that are obscured by conventional plateau-wide analyses, providing a new approach for evaluating motor output in PD.

neuroscience↗

bioRxiv2026

Beyond snapshots: A dynamic framework for continuous motor unit tracking to enhance neurophysiological assessments

Tracking individual motor units (MUs) across multiple testing visits is critical for understanding neuromuscular adaptations and disease progression. However, existing methods fail to account reliably for spatiotemporal variations in motor unit action potentials (MUAPs) and lack validation for longitudinal tracking. Here, we present a robust computational framework for continuous MU tracking that integrates automatic estimation of electrode grid displacements and compensation for MUAP shape variations. Our algorithm demonstrated superior tracking accuracy, capturing 63% and 75% of MUs in the tibialis anterior and medial gastrocnemius, respectively, substantially outperforming state-of-the-art methods. By applying this approach to investigate estradiol-driven neuromuscular plasticity as a model system, we reveal previously undetectable modulations in recruitment thresholds and firing rates, linking hormonal fluctuations to motor unit behavior. Beyond advancing fundamental neuromuscular research, our approach holds promise for enhancing biomarker sensitivity in clinical trials, particularly in conditions such as amyotrophic lateral sclerosis, where reliable MU tracking is paramount. These findings establish a new standard for non-invasive motor unit tracking, unlocking opportunities for longitudinal neurophysiological assessment and evaluation of therapeutics.

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↗

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↗

bioRxiv2022

ACCURATE DECODING OF THE SPINAL CORD OUTPUT IN HUMANS WITH IMPLANTED HIGH-DENSITY ELECTRODE ARRAYS

Invasive electromyography opened a new window to explore motoneuron behaviour in vivo. However, the technique is limited by the small fraction of active motoneurons that can be concurrently detected, precluding a population analysis in natural tasks. Here, we developed a high-density intramuscular electrode for in vivo human recordings along with a fully automatic methodology that could detect the discharges of action potentials of up to 67 concurrently active motoneurons with 99% accuracy. These data revealed that motoneurons of the same pool receive common synaptic input at frequencies up to 75 Hz and that late recruited motoneurons inhibit the discharges of those recruited earlier. These results constitute an important step in the population coding analysis of the human motor system in vivo.

neuroscience↗

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↗

bioRxiv2021

Analysis of motor unit spike trains estimated from high-density surface electromyography is highly reliable across operators

There is a growing interest in decomposing high-density surface electromyography (HDsEMG) into motor unit spike trains to improve knowledge on the neural control of muscle contraction. However, the reliability of decomposition approaches is sometimes questioned, especially because they require manual editing of the outputs. We aimed to assess the inter-operator reliability of the identification of motor unit spike trains. Eight operators with varying experience in HDsEMG decomposition were provided with the same data extracted using the convolutive kernel compensation method. They were asked to manually edit them following established procedures. Data included signals from three lower leg muscles and different submaximal intensities. After manual analysis, 126 {+/-} 5 motor units were retained (range across operators: 119-134). A total of 3380 rate of agreement values were calculated (28 pairwise comparisons x 11 contractions/muscles x 4-28 motor units). The median rate of agreement value was 99.6%. Inter-operator reliability was excellent for both mean discharge rate and time at recruitment (intraclass correlation coefficient > 0.99). These results show that when provided with the same decomposed data and the same basic instructions, operators converge toward almost identical results. Our data have been made available so that they can be used for training new operators.

neuroscience↗