Biology subjects

Pearcey, G. E.

Publications and source records attributed to Pearcey, G. E..

7 recordsLinked to original sources

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

Motor unit discharge properties are modestly influenced by menstrual cycle-related fluctuations in sex hormone concentrations

Concentrations of estradiol (E2) and progesterone (P4), the main female sex hormones, exhibit large fluctuations across the menstrual cycle. Due to their receptors throughout the central nervous system, both hormones have the potential to influence motor function by influencing ionotropic and metabotropic inputs to motor pools, which can be estimated through the neural codes extracted from motor unit discharge patterns. To address key methodological limitations in prior menstrual cycle research on motor output, we established the Motor Units and Sex Hormones (MUSH) collaboration. The objective of this multi-site investigation was to determine whether endogenous fluctuations in estradiol and progesterone influence human motor unit activity. We hypothesized that motor unit discharge rates and persistent inward current (PIC)-related contributions to discharge would be greatest during the late follicular phase, when estradiol concentrations were highest. Fifty females completed a comprehensive protocol involving menstrual cycle and ovulation tracking, serum hormone measurement, and high-density surface electromyographic recordings during isometric contractions to quantify motor unit activity in the early follicular, late follicular, and mid luteal phases. After exclusion of 10 females with either atypical hormone concentration profiles or insufficient motor unit yield, 40 remained in the final analysis. There were significant changes in several motor unit discharge variables between menstrual cycle phases and significant associations with hormone concentrations. Increased estradiol was associated with higher peak discharge rates and ascending discharge rate nonlinearity, while increased progesterone was associated with higher peak discharge rates, more discharge rate hysteresis and ascending discharge rate nonlinearity. Despite reaching statistical significance, the magnitudes of these effects (i.e., effect sizes) were small. Overall, these findings indicate that fluctuations in sex hormones influence motor unit behavior, but the effects are subtle, highlighting the need for well-powered and methodologically rigorous menstrual cycle research. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/699975v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@2eb2c0org.highwire.dtl.DTLVardef@1d98359org.highwire.dtl.DTLVardef@13e772borg.highwire.dtl.DTLVardef@1bb27_HPS_FORMAT_FIGEXP M_FIG C_FIG KEY POINTSO_LIThere are small but detectable differences in motor unit discharge rates between menstrual cycle phases, which are predicted by within-participant fluctuations in estradiol and progesterone. C_LIO_LIDischarge rate patterns that provide estimates of neuromodulatory and inhibitory input suggest that estradiol and progesterone can influence spinal cord circuitry differently than has previously been documented in the brain, highlighting an understudied aspect of female neurophysiology. C_LIO_LIVariability in menstrual cycles and associate hormones makes large-scale, rigorous studies especially valuable in female neuromuscular research. C_LI

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↗

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↗

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↗

bioRxiv2021

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

ObjectiveSuccessive 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. ApproachIn the present study, we propose support vector regression (SVR) as an improved approach for generating 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 ResultCompared 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. SignificanceThe results and methods outlined here provide an improved method for generating smooth 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.

bioengineering↗

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↗