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Experimental Physiology

Wiley

Preprints posted in the last 90 days, ranked by how well they match Experimental Physiology's content profile, based on 21 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Three-dimensional imaging reveals preserved intrinsic contractile function in aging human skeletal muscle fibers

Zepeda, C. S.; Teigen, L. E.; Dobrzycki, I.; Wen, Y.; Sundberg, C. W.

2026-06-12 physiology 10.64898/2026.06.09.730973 medRxiv
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Age-related reductions in muscle fiber size and contractile function, particularly in fibers expressing fast myosin heavy chains, contribute to declines in whole-muscle power. However, methodological limitations in estimating fiber size during contractile experiments have likely contributed to conflicting findings regarding whether reduced single-fiber force and power in older adults reflects their smaller size and/or impaired intrinsic contractile function. To address this, we coupled single-fiber contractile experiments with 3D-imaging in 7 young (19-40yrs) and 6 older (69-84yrs) males to assess intrinsic contractile function and compare agreement between 3D-derived cross-sectional area (CSA) and CSA estimates obtained either in air or solution. Fast fiber CSA from older males were [~]28-45% smaller across measurement conditions compared with young, whereas slow fiber CSA did not differ. Accordingly, absolute force and power of fast fibers were 41% and 37% lower. When normalized to CSA from measurements in air or 3D-imaging, size-specific force and power either did not differ or were greater in older adults, indicating preserved intrinsic contractile function in both fiber types. This was supported by no age-related differences in the rate of tension redevelopment (ktr), a size-independent measure of intrinsic contractile function. In contrast, size-specific force and power calculated using solution-based CSA estimates were lower in older compared with young adults, and Bland-Altman analyses demonstrated the poorest agreement between solution-based and 3D CSA measurements. These findings indicate that intrinsic contractile function is preserved with aging and suggest that methodological differences in CSA measurement contributes to the disparate findings in the literature.

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A novel machine-learning classification model detects oxidative fiber type transitions in a rabbit model of cerebral palsy

Kramer, C. A.; Reedich, E. J.; McCann, H.; Drouin, S.; Sanders, D.; Gonzalez, E.; Ung, T.; Mukisa, A.; Mena Avila, E.; Moline, B. C.; Genry, L. T.; Glennon, J. E.; Quiroga, C.; Dowaliby, L.; DiDonato, C. J.; Quinlan, K. A.; Manuel, M.

2026-06-14 neuroscience 10.64898/2026.06.11.731759 medRxiv
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The distribution of slow-and fast-twitch fiber types in a skeletal muscle heavily influences its physiology. Muscle biopsy studies indicate atypical fiber type composition and fiber size variation in children with cerebral palsy (CP), but subjects have variable treatment history and a variety of muscles affected, so uncertainties remain. In this study, we developed a novel machine-learning classification model to perform high-throughput fiber typing of complete transverse muscle sections. Our XGBoost algorithm-based prediction model yielded a balanced accuracy score of 0.89 and a macro F1-score of 0.89, reflecting its ability to robustly predict muscle fiber type from myosin heavy chain (MyHC) isoform immunofluorescence intensities and morphological descriptors. This is the first reported fiber type classifier to consider hybrid fibers, which is a major advance, considering at least 20% of myofibers are hybrid yet they are routinely overlooked due to difficulty in their detection. We used this classification model to define fiber types of more than 7 million myofibers from flexor-extensor muscle pairs in rabbits that experienced hypoxia-ischemia (HI) injury in utero (modeling CP), and typically developing sham rabbits. We observed an oxidative fiber type shift in flexor muscles (biceps brachii and tibialis anterior) of HI rabbits at postnatal day (P)14-20 and P30-32 (weaning age). This altered fiber type composition imparts reduced contractile force and is amenable to sustained muscle activity; it may reflect chronic low-frequency motor unit activation. This work supports prior clinical reports that developmental trajectories of muscle fibers are disrupted in CP.

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Sex Differences in Motor Unit Properties and Force Steadiness: Insights from Strength-Matched Elbow Flexion

Alaei, P.; Larocque, K. A.; Kim, C.; Jakobi, J.

2026-08-12 physiology 10.64898/2026.08.06.742881 medRxiv
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Sex-related differences in force steadiness are often attributed to maximal strength and motor unit (MU) properties, but their independent contributions remain unclear. This study strength-matched females and males to remove the influence of maximal strength and determine whether MU properties are associated with sex-related differences in force steadiness. Twelve young adults (6 females) were matched for elbow flexion strength (females, 188.6{+/-}15.6 N; males, 199.7{+/-}24.8 N, p=0.4). Both groups performed submaximal isometric elbow flexion contractions at 2.5%, 5%, 10%, 15%, and 25% MVC. The MU recruitment thresholds (RT), discharge rates (MUDR), and coefficient of variation of interspike intervals (CVISI) were measured from intramuscular fine wire electromyography (EMG) electrodes. Force steadiness was quantified as the standard deviation (SD) and coefficient of variation (CV) of force. Across forces, SD and CV of force did not differ between females and males (p>0.05). Females had a higher recruitment threshold than males (p<0.05). Females had higher MUDR at 15% and 25% MVC (p<0.02), while males were higher at 5% MVC (p=0.02). The CVISI was greater in females (p<0.001) and positively correlated with SD of force (r=0.2) and negatively with CV of force (r=-0.2) in females and males. When strength was matched, sex-related differences in force steadiness were not evident. However, females exhibited higher MU recruitment thresholds, MUDR and CVISI. Despite greater CVISI in females, these differences did not translate into greater force fluctuations, suggesting that individual MU discharge variability is not a primary predictor of force steadiness when maximal strength is controlled. NEW & NOTEWORTHYO_LIStrength matching eliminated sex-related differences in elbow flexor force steadiness. C_LIO_LIFemales achieved similar force steadiness using higher MU recruitment thresholds and discharge rates, particularly in the short head of the biceps brachii. C_LIO_LIIn females, the greater variability in motor unit discharge was not associated with reduced force steadiness. C_LI

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Effect of joint velocity and pre-activation on the torque-fascicle length relationship of the vastus lateralis

Tallio, T.; Nordez, A.; Lecarpentier, L.; Dorel, S.

2026-06-29 physiology 10.64898/2026.06.23.734014 medRxiv
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Fascicle operating length during dynamic tasks is often compared to the isometric torque-length relationship, but there is a lack of evidence regarding the influence of joint velocity on optimal fascicle length. Moreover, there is no consensus in the literature regarding the influence of contraction initiation (pre-activation or passive start), although it could alter the interaction between fascicles and the tendon. This study aimed to investigate the effect of joint velocity and pre-activation on the torque-angle and torque-length relationships of the vastus lateralis during mono-articular isokinetic knee extensions. Twenty-one participants performed isometric, isokinetic (50{degrees}.s-1 to 450{degrees}.s-1), and isokinetic knee extensions with maximal isometric or eccentric pre-activation at 100{degrees}.s-1 and 300{degrees}.s-1. Torque, joint angle, fascicle length, and electromyographic activity of the quadriceps femoris muscles were recorded during contractions and then used to model the torque-angle and torque-length relationships. We were able to successfully fit the torque-angle and torque-length relationships (R{superscript 2}=0.93 and R{superscript 2}=0.92, respectively). A main effect of velocity was detected regarding the optimal angle (p<0.05), but no significant change was observed for the optimal fascicle length. Isometric pre-activation induced a reduction in maximal torque production compared with eccentric pre-activation and passive conditions at both isokinetic velocities (p<0.001), with no change in muscle activity. Our results suggest that muscle-tendon interactions may permit a dissimilar behavior between the torque-angle and the torque-fascicle length relationships. The reduction in torque following isometric pre-activation may be related to a contraction history-dependent phenomenon. NEW & NOTEWORTHYWe demonstrated that, at a given joint angle, increasing velocity altered fascicle operating length without shifting optimal fascicle length, likely because of muscle-tendon interactions. We also showed that maximal isometric pre-activation before a concentric contraction reduced mean and maximal torque during the isokinetic phase compared with eccentric pre-activation or no pre-activation. This effect may be linked to contraction history, since muscle activity did not differ between conditions.

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Acute molecular and chronic vastus lateralis adaptations to lengthened partial versus full range of motion resistance training in previously trained males

Plotkin, D. L.; Tiede, D. R.; Gotla, T.; Kelly, J.; Rollin, M.; Queneua, J.; Wilborn, C. D.; Meyer Vega, M.; Robles-Cerdas, V.; Bashir, A.; Beyers, R. J.; Esquivel, C. A.; Mobley, C. B.; Babl, R.; Kavazis, A. N.; Beck, D. T.; Baweja, H. S.; Vann, C. G.; Swinton, P. A.; Taylor, L. W.; Roberts, M. D.

2026-06-09 physiology 10.64898/2026.06.04.730150 medRxiv
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This study examined how lower-body lengthened partial (LP) versus full range of motion (FULL) resistance training affects acute post-exercise signaling, chronic hypertrophy, and cellular adaptations of the vastus lateralis (VL) muscle in resistance-trained men. Eight males (22{+/-}1 years old, 5.6{+/-}1.4 years training) completed a crossover study whereby VL biopsies were collected pre-exercise and 0, 3, and 24 hours following LP and FULL leg extension bouts for transcriptomic and anabolic signaling analyses (Experiment 1). Another 16 males (26{+/-}5 years old; 8.0{+/-}4.9 years training) completed an 8-week, twice-weekly lower-body intervention using a within-subject design (Experiment 2). One leg was assigned to FULL and the contralateral leg to LP training across three exercises (leg press, leg extension, and lying leg curl). Pre- and post-intervention outcomes included VL muscle cross-sectional area (mCSA) summed across five equidistant MRI-derived transverse slices and mid-thigh VL biopsy outcomes. As a secondary outcome, other hip and thigh muscles from Experiment 2 MRI scans were assessed. Condition x Time interactions for all outcomes were assessed using linear mixed-effects models. In Experiment 1, both conditions produced similar time-dependent changes in the VL transcriptome and anabolic (mTORC1 and Hippo) signaling, but minimal between-protocol interactions. In Experiment 2, VL summed mCSA significantly increased over time (mean change: 9.3 cm{superscript 2}, 95% CI [6.8, 11.8], P<0.001), but there was no clear evidence of differential change between protocols (LP-FULL change: -1.4 cm{superscript 2}, 95% CI [-6.1, 3.8], P=0.640). Additionally, no significant interactions existed for type I fiber CSA (P=0.476), type II fiber CSA (P=0.350), type I fiber myonuclei (P=0.813), type II fiber myonuclei (P=0.589), type I and II satellite cell number (P=0.102 and P=0.797, respectively), or total RNA content (P=0.537). Despite these null VL-centric findings, secondary Experiment 2 analyses provided some evidence that whole hamstring hypertrophy was greater following LP versus FULL (LP-FULL change: 3.9 cm{superscript 2}, 95% CI [-0.2, 7.9], P=0.058). In conclusion, 8 weeks of LP and FULL resistance training broadly elicit similar acute and chronic VL responses in previously trained men, though secondary hamstring findings suggest that differential responses may depend on exercises included in the resistance training program.

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Unilateral resistance training induces greater rate coding adaptations in high-threshold motor units during maximal voluntary contractions

Lecce, E.; Amoruso, P.; Del Vecchio, A.; Casolo, A.; Felici, F.; Farina, D.; Bazzucchi, I.

2026-07-01 physiology 10.64898/2026.06.26.734811 medRxiv
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Resistance training lasting a few weeks increases maximal force mainly through neural adaptations that enhance the drive from the nervous system to muscle. While these adaptations have been well documented at the motor unit (MU) level during submaximal force contractions, the mechanisms underlying force increases during maximal voluntary contractions are poorly understood. This is due to a classic technical limitation in tracking MUs longitudinally during maximal force tasks. Here, we solved this technical challenge, enabling the investigation of MU adaptations during MVCs in both the trained and untrained limbs following unilateral resistance training. High-density surface electromyography was recorded from the biceps brachii of both limbs before and after a 4-week unilateral resistance-training intervention, and the same MUs were longitudinally tracked across sessions during MVCs by concatenation of three MVC trials of ~5-s each.Unilateral training increased maximal force in the trained limb (+16%) and induced strength transfer to the untrained limb (+8%). In both limbs, maximal contractions after training were characterized by greater EMG amplitude, faster muscle-fiber conduction velocity, and higher MU discharge rates, indicating enhanced neural drive to the motoneuron pool. These adaptations were strongly associated with improvements in maximal force (R2 > 0.7 for all). Importantly, longitudinal MU tracking revealed a non-uniform adaptation across the MU pool: MUs with higher baseline conduction velocity, indicative of higher recruitment threshold, exhibited the largest pre-post increases in discharge rate, whereas lower-threshold units showed smaller changes. Collectively, these findings demonstrate that gains in maximal force and their transfer to the untrained limb are primarily mediated by enhanced rate coding of higher-threshold MUs during MVCs.

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Recurrent inhibition, not presynaptic inhibition, contributes to the velocity-dependent control of motoneuron output during eccentric contractions

Colard, J.; Nosaka, K.; Latella, C.; O'LOUGHLIN, J.; Cattagni, T.; Jubeau, M.

2026-07-24 neuroscience 10.64898/2026.07.20.739651 medRxiv
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It is well documented that both motoneuron output and the effectiveness of activated Ia afferents to discharge soleus -motoneurons decrease during eccentric (muscle lengthening) contractions. Evidence suggests that these modulations can be explained by recurrent inhibition and greater presynaptic inhibition of Ia afferents. However, the influence of angular velocity on the modulation of the effectiveness of activated Ia afferents to discharge -motoneurons observed during eccentric contractions remains unclear. We investigated the influence of angular velocity on spinal mechanisms involved in the effectiveness of activated Ia afferents to discharge -motoneurons during eccentric plantar flexor contractions using 16 healthy adults. We used both simple and conditioned Hoffmann reflex with different conditioning techniques to assess presynaptic inhibition, heteronymous Ia facilitation and heteronymous recurrent inhibition coupled with electromyography during eccentric contractions of the plantar flexors at three angular velocities. Our results showed that during eccentric contractions, the effectiveness of Ia afferents to discharge -motoneurons was lower at 90{degrees}{middle dot}s-{superscript 1} than 60{degrees}{middle dot}s-{superscript 1} and 20{degrees}{middle dot}s-{superscript 1} angular velocities. A similar velocity-dependent pattern was observed for heteronymous recurrent inhibition, decreasing at 90{degrees}{middle dot}s-{superscript 1} when compared with 60{degrees}{middle dot}s-{superscript 1} and 20{degrees}{middle dot}s-{superscript 1}. In contrast, presynaptic inhibition of Ia afferents was not different between the velocities. These demonstrate a differential influence of angular velocity on spinal recurrent inhibitory mechanisms during eccentric contractions and support distinct functional roles of recurrent and presynaptic inhibition in modulating -motoneurons discharge with increasing movement velocity. The findings provide new insights into the velocity-dependent and mechanism-specific modulation of spinal inhibitory circuits during eccentric contractions. KEY POINTSO_LIDuring eccentric contractions in soleus muscle, the effectiveness of activated Ia afferents to discharge -motoneurones decreases with increasing angular velocity, indicating a velocity-dependent modulation. C_LIO_LIPresynaptic inhibition of Ia afferents does not differ between angular velocities, suggesting that it does not contribute to the observed changes. C_LIO_LIHeteronymous recurrent inhibition from the quadriceps to the soleus increases with angular velocity, indicating that increasing movement velocity promotes a functional reorganization of intermuscular recurrent inhibition. C_LIO_LIThese findings suggest a differential functional role of the two spinal inhibitory mechanisms, indicating that increasing angular velocity primarily influences recurrent postsynaptic inhibition rather than presynaptic inhibition. C_LI

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Progressive plyometric training improves jumping performance and reduces force-velocity imbalance in collegiate volleyball players

Wu, H.; Xi, X.; Li, J.

2026-07-30 physiology 10.64898/2026.07.22.740194 medRxiv
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Few studies have focused on plyometric interventions lasting over 24 weeks in team-sport athletes, and little research has validated the practical utility of personalized force-velocity assessment. A total of 36 university volleyball athletes (21.35{+/-}1.87 years) were randomly allocated into either a 32-week plyometric training group (PT, n=18) or a low-intensity active control group (CON, n=18); 34 players completed the trial (17 per group). PT completed three weekly training sessions, while CON maintained routine technical practice and general low-intensity conditioning. CMJ height, RSImod, and force-velocity profiles (F, V, peak power, FV imbalance) were evaluated at baseline and at weeks 8, 16, 24, and 32. PT increased CMJ height from 33.1{+/-}4.8 cm to 38.4{+/-}5.2 cm, a net gain of 5.3 cm (p<0.01, d=0.99, 95% CI [0.57, 1.41]); CON showed negligible change (+0.5 cm, p=0.68). The PT group also improved RSImod by 31.6% (d=0.87, 95% CI [0.45, 1.29], p<0.01) and peak power by 18.4% (d=0.76, 95% CI [0.35, 1.17], p=0.004). Meanwhile, FV imbalance dropped markedly by 31.4%, from 28.3% to 19.4% (d=-0.68, 95% CI [-1.09, -0.27], p=0.024). No significant F-V changes occurred in CON. The reduction in FV imbalance correlated moderately with CMJ gain (r= - 0.53, p=0.024), whereas the change in peak power did not (r=0.21, p=0.39). Overall, 32 weeks of periodized plyometric training enhanced jump performance, reactive strength, and power, and reduced the force-velocity (FV) imbalance by approximately 31%. The magnitude of improvements in jump performance (16%) and FV imbalance reduction (31%) observed in this 32-week periodized program fall within a similar range to previously reported effects of individualized F-V training (14% and 40%, respectively). However, direct numerical comparisons are confounded by differences in study design, population, and methodology; head-to-head trials are needed.

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Muscle-specific motor unit firing characteristics in elbow flexors and extensors after cervical spinal cord injury

Benedetto, A.; Jenz, S.; Farley, M.; Heit, B.; Sangari, S.; Beauchamp, J. A.; McPherson, L.; Heckman, C.; Perez, M.; Pearcey, G.

2026-06-08 neuroscience 10.64898/2026.06.03.729825 medRxiv
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Individuals with cervical spinal cord injury (SCI) often exhibit asymmetric recovery of upper-limb function, with greater weakness in elbow extensors than flexors. To determine whether muscle-specific changes in motor unit (MU) behavior contribute to this disparity, we identified MU firing instants from high-density surface electromyography to characterize MU firing characteristics in the biceps brachii (BIC) and triceps brachii (TRI) of individuals with cervical SCI (n = 20) and non-injured controls (n = 18). We quantified rate-coding behavior and metrics related to persistent inward currents (PICs), including onset-offset hysteresis ({Delta}F), ascending firing rate nonlinearity, and self-sustained firing. At the group level, BIC MUs in SCI participants showed reduced rate coding and altered ascending firing rate nonlinearity relative to controls. In contrast, TRI MUs showed no clear group-level differences. However, subgroup analysis revealed that SCI participants with low-strength during extension (n = 9) exhibited lower {Delta}F and longer self-sustained firing durations in TRI MUs than those with high-strength (n = 6). In BIC, SCI participants with low-strength during flexion (n = 8) showed reduced rate-coding behavior relative to high-strength SCI participants (n = 9), with no differences in PIC-related metrics. Together, these results demonstrate muscle-specific alterations in MU firing after cervical SCI that may relate to strength recovery or preservation and underscore the need for nuanced analyses in heterogeneous SCI populations. Key pointsO_LIRate coding and nonlinear firing behaviors are significantly altered in the biceps brachii, but not triceps brachii, of participants with cervical spinal cord injury. C_LIO_LIStrength based subgroup analyses revealed muscle-specific differences in motor unit behaviors that may be associated with strength preservation or recovery following spinal cord injury. C_LIO_LIFunctional heterogeneity following spinal cord injury may mask group differences in motor unit behaviors and warrants careful interpretation of results of future studies. C_LI

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Supershoes or Superhumans? A controlled analysis of sex-specific road-running performance evolution in the era of advanced footwear technology

Blattmann, L.; Hamacher, D.; Tucker, R.; Healey, L.; Mason, J.

2026-07-03 physiology 10.64898/2026.07.03.736031 medRxiv
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Advanced footwear technology (AFT) improves running economy and is widely credited with recent performance improvements in road running, with observational analyses consistently demonstrating that women have improved more than men. In contrast, laboratory studies generally report similar running economy responses to AFT in both sexes, leaving the observational-experimental divergence unresolved. A fundamental limitation of observational work is the absence of a control condition, making it impossible to separate AFT-related gains from concurrent performance trends. We addressed this by comparing performances between pre-AFT (2009-2015) and AFT (2017-2024) eras across road-running events (10km, half marathon, marathon) and throwing events (shot put, discus, javelin, hammer), the latter serving as an active control condition subject to the same broad athletic trends but unaffected by footwear technology. The top 50 performances per event, era, and sex were converted to World Athletics points and analysed using linear mixed-effects models. Performances improved significantly between eras ({beta} = 0.294, p < .001), with gains substantially larger in road running than in throwing ({beta} = 0.731, p < .001). The sex-specific pattern of improvement also differed between event categories (era x event type x sex interaction, {beta} = 0.786, p < .001): road-running improvements were greater in women than men (4.51% vs 2.62%), whereas throwing improvements did not differ by sex (0.93% vs 1.14%). These findings suggest that AFT benefits women more than men in competition, whether through a greater physiological response or more effective translation of economy gains to race performance, and suggest current laboratory protocols may be insufficiently sensitive to detect potential sex-specific effects.

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Cross-Sectional Physiological and Neuromuscular Profiling of Elite and Recreational University Badminton Athletes: Preliminary Benchmarks for Exercise-Based Injury Risk Stratification

Ahmed, H.; Moznuzzaman, M.; Hasan, M. K.; Shohag, J. A.; Hasan, M.; Abdullah, A.; Boby, F. A.

2026-06-09 biophysics 10.64898/2026.06.02.729234 medRxiv
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Background and PurposeBadminton imposes considerable cardiovascular and musculoskeletal stress. Physiological profiling can identify modifiable injury risk factors and inform exercise-based prevention and rehabilitation. This study compared cardiovascular recovery, neuromuscular activation, and limb strength between elite and recreational male university badminton players to derive preliminary physiological benchmarks for injury risk stratification and exercise rehabilitation guidance. MethodsForty male athletes (20 elite: national/university representatives with [&ge;]5 years of competitive experience; 20 recreational: <3 years of experience) completed assessments of heart rate recovery (HRR), biceps brachii surface electromyography (sEMG; SENIAM protocol), handgrip strength (JAMAR dynamometry), and maximal bodyweight squat repetitions. Independent-sample t-tests with Cohens d ( = 0.05) and Pearson correlations were applied. ResultsElite players demonstrated significantly greater handgrip strength (49.00{+/-}6.12 vs. 39.00{+/-}5.45 kg, p = 0.001, d = 1.72) and lower-limb (LL) strength (60.35{+/-}11.29 vs. 41.75{+/-}6.72 repetitions, p < 0.001, d = 1.96). Normalized sEMG root mean square (RMS) was higher in elite athletes during flexion (11.56{+/-}4.16% vs. 7.26{+/-}5.15%, p = 0.004, d = 0.94) and extension (12.67{+/-}4.56% vs. 7.85{+/-}5.73%, p = 0.003, d = 0.94). HRR did not differ significantly between groups (p = 0.17, d = 0.43, observed power = 0.34). Elite players nonetheless showed a more favorable recovery distribution. sEMG -HRR correlations were weak and non-significant in both groups. ConclusionsElite badminton players exhibit a distinct physiological profile of greater strength and more efficient neuromuscular activation. These preliminary cross-sectional findings may support the design of exercise-based injury-prevention and rehabilitation in university badminton.

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Understanding the biomechanical and physiological responses to Advanced Footwear Technology in well-trained male and female runners

Albertus, Y.; Leith, D.; Berg, O.; Barrons, Z. B.; Tam, N.

2026-06-24 physiology 10.64898/2026.06.19.732297 medRxiv
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Advanced footwear technology (AFT) has transformed competitive running, yet individual and sex-specific responses to different AFT models remain unclear, particularly near race pace. This study examined running economy (RE) and gait biomechanics in response to three top-tier AFT models (Shoe A: adidas Pro Evo 2; Shoe B: Nike Alphafly 3; Shoe C: On CloudBoom Strike 2) in 14 male and 12 female well-trained runners at sex-specific submaximal speeds (16 and 14 km{middle dot}h-{superscript 1}). RE, spatiotemporal, and joint kinematic/kinetic data were collected via indirect calorimetry, accelerometry, and three-dimensional motion capture with force platforms. RE was significantly lower in Shoe C than Shoe A (males: 2.1%; females: 1.4%) and Shoe B (males: 1.9%; females: 0.9%), with 73% of runners responding favourably to Shoe C, a more consistent response than previously reported. Despite being lightest, Shoe A produced the poorest RE, challenging conventional mass-economy assumptions. Biomechanically, Shoe C elicited greater impact magnitude, lower ankle quasi-stiffness, and greater ankle angular velocity during early stance. Female runners showed smaller RE improvements, potentially related to lower running velocity and body mass limiting midsole engagement. The most efficient AFT enabled these well-trained runners to be more spring-like through tolerating higher forces and faster angular velocities without greater demand on metabolic cost.

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Spinal nociceptive denervation impedes subsequent chronic autonomic remodeling after myocardial infarction in male swine

Van Weperen, V.; Hoang, J. D.; Jani, N.; Avasthi, S.; Chan, C. A.; Cao, K.; Lokhandwala, Z. A.; Emamimeybodi, M.; Atmani, K.; Vaseghi, M.

2026-07-05 physiology 10.1101/2025.03.28.645120 medRxiv
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After myocardial infarction (MI), pathological autonomic remodeling, including vagal dysfunction and sympathoexcitation, occurs and predisposes to ventricular arrhythmias (VT/VF). The underlying factors that drive this remodeling, including the observed neuroinflammation and glial activation, remain unknown. We hypothesized that sympathetic nociceptive afferents underlie this remodeling post-MI. Epidural resiniferatoxin (RTX, to ablate sympathetic cardiac afferent neurons) vs. saline was administered in pigs prior to MI and autonomic and electrophysiological effects assessed four to six weeks post-infarction. Acute effects of afferent ablation after chronic MI were also assessed in a separate group of animals. Baroreflex sensitivity and vagal tone, as measured by parasympathetic neuronal activity and cardiac nociceptive responses, were improved in infarcted animals which received epidural RTX prior to MI. These animals also demonstrated reduced spinal cord inflammation and glial activation, downregulation of circulating stress and inflammatory pathways, and stabilization of electrophysiological parameters, with reduced VT/VF-inducibility. Epidural RTX after chronic MI also acutely restored vagal function and decreased VT/VF. These data suggest that cardiac spinal nociceptive afferents directly contribute to VT/VF susceptibility and MI-induced autonomic remodeling, including oxidative stress, inflammation, glial activation, and reduced vagal function, providing novel insights into the causal role of these afferents in driving sympathovagal imbalance after MI.

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Frequency-Domain Analysis Links Autonomic Disruption to Renal Autoregulatory Failure after Spinal Cord Injury

Tsang, A.; Kaur, G.; Tom, V. J.; Gurkan-Cavusoglu, E.; Osei-Owusu, P.

2026-07-03 physiology 10.64898/2026.06.29.735393 medRxiv
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Spinal cord injury (SCI) disrupts supraspinal autonomic pathways that regulate cardiovascular function, producing marked blood pressure instability and contributing to secondary injury in peripheral organs. The kidney is particularly vulnerable to these disturbances because renal blood flow (RBF) depends on tightly regulated interactions between neural, myogenic, and vascular control mechanisms. However, how SCI level and chronicity alter dynamic renal autoregulation remains poorly defined. Here, we investigated the effects of high- and low-thoracic SCI on renal hemodynamic control using in vivo blood pressure and RBF recordings in female mice. Hemodynamics were assessed at baseline and during acute sympathetic stimulation induced by norepinephrine (NE; 10 g/kg, i.v.) at 24 h and 4 wk following spinal cord transection at thoracic level 3 (T3) or thoracic level 10 (T10). Time-domain analyses quantified systolic blood pressure recovery, while frequency-domain analyses were used to resolve myogenic and sympathetic contributions to RBF regulation. High-thoracic SCI caused marked disruption of renal vascular responses to acute hypertension, producing paradoxical increases in RBF during NE-induced pressure elevations and sustained reductions in baseline and evoked RBF activity within frequency ranges associated with myogenic and sympathetic vasomotion. These impairments were most pronounced during the chronic phase of injury, consistent with loss of dynamic autoregulatory control and vascular remodeling. In contrast, low-thoracic SCI preserved baseline renal vasomotor activity and demonstrated recovery of dynamic autoregulatory responses over time. These findings identify SCI level and chronicity as critical determinants of renal microvascular regulation and demonstrate that high-thoracic SCI produces persistent autonomic-vascular uncoupling. This disruption of dynamic renal autoregulation represents a previously underappreciated mechanism of secondary organ vulnerability following neurotrauma.

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Spinal reflex modulation in the pelvic floor muscles through sensory stimulation from the lower limb

Sun, Y.; Cunningham, C.; Yang, J. F.; Zehr, E. P.; Lam, T.

2026-06-12 neuroscience 10.64898/2026.06.09.730985 medRxiv
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The pelvic floor muscles (PFM) are critical for maintaining continence and are a primary target of physiotherapy training to manage urinary incontinence. PFM training relies on voluntarily activating this muscle group, limiting its translation to neurological populations where recovery of bladder function is a priority. Indirect evidence suggests that sensory feedback from the lower limb can modulate PFM activity, which may provide alternative strategies for PFM training. Cutaneous reflexes have been used as a proxy to study how sensory inputs from the skin influence motoneuron excitability. To explore the feasibility of eliciting cutaneous reflexes in the PFM and their role in controlling PFM activity, this study examined: 1) the input-output relationship and 2) the nerve-specificity of PFM cutaneous reflex responses from tibial and superficial peroneal nerve stimulation. Twenty-one neurologically intact adults participated in this study. We recorded PFM and lower leg muscle electromyography while participants received cutaneous stimulation to the right distal tibial nerve, bilateral distal tibial nerve, or right superficial peroneal nerve in a standing position. We delivered stimulation at the intensity below motor threshold (MT), 1.2 x MT and 1.5 x MT and quantified tibial-PFM reflex amplitude over a 50-150 ms window after stimulation. PFM reflex responses were evoked from both nerves stimulation. Reflex amplitude increased with stimulus intensity with tibial nerve stimulation but not with superficial peroneal nerve stimulation. Bilateral tibial nerve stimulation evoked larger responses compared to unilateral stimulation. These findings support the existence of neural connections between lower limb afferents and the PFM, and open up possibilities for designing rehabilitation strategies to manage pelvic health conditions in people with neurological disorders. New & NoteworthyO_LICutaneous sensory feedback from the foot, specifically that related to limb loading, can evoke reflex responses in the pelvic floor muscles C_LIO_LINerve-specific modulation was observed. Reflex amplitudes in the pelvic floor muscles increased with tibial nerve stimulation intensity but not with superficial peroneal nerve stimulation. C_LI

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Height-induced postural threat selectively facilitates spinal reflex in the tibialis anterior muscle during quiet standing

Takahashi, R.; Kaneko, N.; Ishikawa, K.; Sato, K.; Mashiki, Y.; Nakazawa, K.

2026-08-10 neuroscience 10.64898/2026.08.04.742625 medRxiv
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Long-latency stretch reflex and corticospinal excitability in the tibialis anterior muscle (TA) are facilitated when balance is threatened, even without background TA activity, suggesting supraspinal modulation as preparatory tuning for ankle stabilization. However, it remains unclear whether such tuning is evident at the spinal level and specific to the TA among lower-limb muscles. We therefore examined the effects of height-induced postural threat on multi-segmental monosynaptic spinal reflexes (MMR) in lower-limb muscles during quiet standing. Seventeen healthy young males performed 90-s standing tasks under three postural threat conditions, created by combining real and virtual reality (VR) heights: (1) Low-threat (real ground & VR ground), (2) Medium-threat (real table & VR ground), and (3) High-threat (real table & VR bridge). During each condition, transcutaneous spinal cord stimulation (tSCS) was applied to the lumbar spine to elicit MMR in lower-limb muscles. Electromyograms (EMG) were recorded from six muscles of the right leg: vastus medialis (VM), biceps femoris (BF), TA, soleus (SOL), medial (MG), and lateral gastrocnemius (LG). MMR excitability was quantified as peak-to-peak EMG amplitude. Fear ratings and electrodermal activity were higher in High-threat than Low-threat (all p < 0.05), confirming successful threat induction. Peak-to-peak EMG amplitude in the TA was significantly higher in High-threat than Low-threat (17.1% increase, p = 0.0393), whereas background TA activity remained absent across conditions. These results indicate that TA has unique function to facilitate spinal excitability as a preparatory tuning for ankle stabilization. Key pointsO_LIPrevious studies have shown the supraspinal facilitation of the tibialis anterior muscle without background muscle activation as a preparatory tuning for ankle stabilization. C_LIO_LITo test the hypothesis that such tuning is also evident at the spinal level and specific to the tibialis anterior muscle, this study examined whether height-induced postural threat modulates multi-segmental monosynaptic reflex excitability in lower-limb muscles using transcutaneous spinal cord stimulation. C_LIO_LIElectrodermal activity and fear ratings increased under height-induced postural threat, confirming the successful induction of postural threat. C_LIO_LIUnder height-induced postural threat, the multi-segmental monosynaptic reflex was selectively facilitated in the tibialis anterior muscle, while its background activity remained absent. C_LIO_LIOur findings demonstrate selective facilitation of spinal excitability in the tibialis anterior muscle, which may serve as preparatory tuning for ankle stabilization under threat to balance. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/742625v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@ca21f3org.highwire.dtl.DTLVardef@7b1679org.highwire.dtl.DTLVardef@1007191org.highwire.dtl.DTLVardef@1ff88a_HPS_FORMAT_FIGEXP M_FIG C_FIG Abstract figure legendWhen balance is threatened, corticospinal excitability and long-latency stretch reflex in the tibialis anterior muscle (TA) are facilitated even in the absence of background TA activity, suggesting supraspinal preparatory tuning for ankle stabilization. This study tested the hypothesis that such facilitation is also expressed at the spinal level and is specific to the TA. Participants completed 90-s quiet standing trials under three different height-induced postural threat conditions. During each trial, transcutaneous spinal cord stimulation was delivered over the lumbar spine to elicit multi-segmental monosynaptic reflexes (MMR) in multiple lower-limb muscles. High-threat condition increased fear ratings and electrodermal activity, indicating successful threat induction. Moreover, MMR excitability was selectively increased in the TA under High-threat condition despite the absence of background TA activity. These findings suggest that spinal facilitation is selectively expressed in the TA and may reflect preparatory tuning for ankle stabilization under threat to balance.

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Unimanual fatigue increases muscle excitation and local metabolic activity in the resting contralateral forearm

Hinkle, L. J.; Scheuermann, B. C.; Ade, C. J.; Barstow, T. J.; Carr, J. C.

2026-07-06 physiology 10.64898/2026.06.30.735603 medRxiv
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Intense unilateral muscle contractions evoke measurable activity within the contralateral neuroaxis, which can be detected with surface electromyographic activity in the resting homologous muscle. Physiological mirror activity (PMA), the unintentional increase in contralateral muscle excitation, has been implicated in cross-limb interactions and adaptations. Despite longstanding observations of PMA, it remains unknown whether this low-level muscle excitation influences local muscle metabolism. We addressed this question using a vascular occlusion test in 10 healthy adults. Surface electromyography and near-infrared spectroscopy-derived measures of tissue oxygen saturation and muscle oxygen consumption (mVO2) were obtained from the resting left forearm during vascular occlusion at rest and during fatiguing unimanual contractions of the right hand. PMA in the contralateral resting arm was greater during unimanual fatigue than during rest (mean difference: 8.9%AA, 95% CI: 4.1 to 13.8; p = 0.002, g = 1.20). This increase was accompanied by a steeper rate of tissue oxygen desaturation (mean difference: -0.132 %{middle dot}s-1, 95% CI: -0.227 to -0.037; p = 0.012, g = -0.91) and greater mVO2 (mean difference: 0.188 mL O2{middle dot}min-1{middle dot}100 g-1, 95% CI: 0.057 to 0.320; p = 0.010, g = 0.94). Greater PMA was associated with both a faster rate of oxygen desaturation (r = -0.85, 95% CI: -0.96 to -0.46, p = 0.002) and greater mVO2 (r = 0.78, 95% CI: 0.28 to 0.94, p = 0.008). These findings suggest that PMA is accompanied by increased local metabolic demand, consistent with a coupling between unintentional muscle excitation and oxygen extraction in the resting limb.

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Adaptation to postural perturbations under fatigue produces persistent changes in neuromuscular coordination

Nardon, M.; Alessandro, C.; Singh, T.; Bertucco, M.

2026-06-30 neuroscience 10.64898/2026.06.25.734469 medRxiv
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Postural control depends on the ability to adapt motor responses to changing environmental and physiological conditions. Neuromuscular fatigue (NMF) is known to alter balance and muscle activation patterns, yet its effects on motor adaptation during whole-body postural tasks and on the persistence of learned strategies remain unclear. This study investigated whether localized NMF of the ankle dorsiflexors influences adaptation to a novel postural perturbation task and whether learning under fatigue induces persistent changes during subsequent re-exposure. Twenty-five healthy young adults were assigned to either a fatigue (FAT) or no-fatigue (NoFAT) group and completed two experimental sessions separated by 48-72 h allowing recovery from acute fatigue for fatigued group. Participants adapted to repeated mechanical perturbations while standing upright, while ground reaction forces and electromyographic activity of lower-limb muscles were recorded. NMF did not impair overall adaptation performance, as both groups exhibited similar reductions in performance error across practice. However, participants exposed to fatigue exhibited altered postural recovery dynamics, characterized by a reduced return toward the initial posture following perturbation release. These differences persisted during re-exposure on the subsequent day, despite the absence of acute fatigue. In parallel, NMF modified muscle activation and coactivation patterns involving both fatigued and non-fatigued muscles, several of which were retained during re-exposure. These findings indicate that the central nervous system preserves successful adaptation to postural perturbations under fatigue by reorganizing neuromuscular coordination and stabilization strategies. Learning under fatigue therefore influences not only immediate motor execution, but also shapes the longer-term representation of postural control strategies.

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Human decompression in real time: programmable ultrasound imaging during hyperbaric exposure

Currens, J.; Natoli, M. J.; Eltz, K.; Morales, G.; Bautista, K. J. B.; Dayton, P. A.; Lance, R.; Oralkan, O.; Yamaner, F. Y.; Moon, R. E.; Papadopoulou, V.

2026-07-27 physiology 10.64898/2026.07.22.737513 medRxiv
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The formation of inert gas bubbles during decompression can lead to decompression sickness (DCS), a major operational risk for divers, compressed-gas workers, astronauts, and high-altitude aviators. In diving, DCS risk is typically inferred from post-dive ultrasound detection of venous gas emboli (VGE), precluding modification of decompression schedules based on real-time physiological feedback. Two-dimensional ultrasound imaging could provide additional insight into decompression-related physiological changes; however, its use in hyperbaric environments has been largely precluded by fire risk associated with elevated oxygen partial pressures (ppO2) in enclosed spaces. Here, we developed a workflow for operating a programmable ultrasound system under hyperbaric conditions and acquiring ultrasound data from the subclavian vein and calf muscle during decompression. A total of 42 dives were conducted by 26 individuals using a previously characterized dive profile to 132 feet seawater (FSW) for 20 min with 9 min of decompression. Three exposure conditions were evaluated: non-exercising, exercising, and a brief pause at 20 FSW during compression. Twelve dives included programmable ultrasound imaging during decompression. Post-dive VGE responses were consistent with prior reports while demonstrating substantial inter-individual variability and sensitivity to modest profile modifications. VGE were detected in the subclavian vein during decompression in two participants and subsequently confirmed by post-dive echocardiography. Calf muscle ultrasound brightness typically increased from pre-dive to decompression measurements, before decreasing below baseline in the 120 min post dive measurement period. These findings demonstrate the feasibility of programmable ultrasound imaging during human decompression and establish a practical framework for ultrasound operation under hyperbaric conditions. This approach may support future physiological studies and development of automated decompression monitoring technologies. New and NoteworthyThis study demonstrates the first use of a programmable ultrasound system to acquire and quantitatively analyze ultrasound data during human decompression. The approach enabled direct visualization of venous gas emboli during decompression and revealed calf muscle ultrasound signal changes, providing a new tool for investigating physiological responses during decompression that are not accessible through conventional post-dive monitoring.

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The Limited Range of Motion of the Knee Does Not Fully Explain the Altered Neural Control of Plantar Flexors During Gait in Non-Neurological Knee Flexion Contracture

Cruz-Montecinos, C.; Boonstra, T. W.; Maas, H.

2026-06-11 neuroscience 10.64898/2026.06.08.730170 medRxiv
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Knee flexion contracture (KFC) may occur in the late stages of arthropathies, including osteoarthritis and haemophilic arthropathy. The impact of KFC on neuromuscular control remains unclear, particularly for the affected ankle plantar flexors. Surface electromyography (EMG) is widely used to assess muscle activation patterns, whereas intermuscular (EMG-EMG) coherence provides insight into common neural input. In this study we compared the neural control of ankle plantar flexors during gait between individuals with haemophilia and KFC (chronic; n = 8), and healthy individuals without (control; n = 15) and with an artificial constraint (artificial; n = 15). Bipolar EMG from plantar flexors was recorded during 30-m overground walking (1 m/s). Intermuscular coherence was estimated at 8-60 Hz during the stance phase and significance was determined using a permutation method. The chronic group showed greater knee flexion than controls (24-29 deg vs 2-20 deg), higher EMG amplitude at foot contact, and increased intermuscular coherence in the alpha (8-12 Hz) and beta (12-30 Hz) bands at mid-stance. Despite comparable sagittal knee kinematics between constrained conditions (chronic: 24-29 deg; artificial: 20-32 deg), early-stance EMG amplitude and mid-stance beta-band intermuscular coherence were higher in the chronic group across plantar-flexor pairs. Increased plantar-flexor activation in the chronic group suggests higher neural drive, while higher intermuscular coherence reflects greater common input to the plantar flexors. These findings indicate that limited ROM alone does not explain the altered neural control of plantar flexors, suggesting neural adaptations associated with non-neurological chronic KFC.