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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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Contraction type dependence of serial sarcomere addition following resistance training

Rilling, A.; Zero, A. M.; Kirkup, A.; Stratford, M.; Chapman, K.; Hinks, A.; Power, G. A.

2026-10-06 physiology 10.64898/2026.09.29.755478 medRxiv
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Longitudinal muscle growth occurs through the addition of sarcomeres in series, a process termed serial sarcomerogenesis. To investigate contraction mode dependence of sarcomerogenesis in Sprague-Dawley rats (n=36, 14 to18 weeks, ~468g), we compared the effects of isometric, eccentric, and concentric training (4 to 6 weeks; 3 times/week) on morphological and mechanical adaptations of the plantar flexors. Isometric training was performed at a joint angle corresponding to the plateau nearing the descending limb of the force length relationship, eccentric contractions began at a shorter muscle length and lengthened to this same joint position, and concentric contractions started at this lengthened position but then actively shortened. Owing to the rapid regulation of serial sarcomere number the 4-and 6-week timepoints were collapsed. While force output increased across all training modes (+16%; p<0.05), longitudinal muscle growth was regulated by contraction type. Both isometric and eccentric training were highly effective at increasing serial sarcomere number when optimal loading conditions (high forces at longer lengths) are provided (+7-9%; p<0.05). Concentric training, even when initiated at long lengths with high forces was not an effective stimulus for longitudinal remodelling (+2%; p>0.05). Therefore, these findings identify the mechanical loading environment associated with isometric and eccentric training as a key driver of serial sarcomerogenesis.

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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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Sarcomere length, fascicle length, and serial sarcomere number are preserved in paretic hindlimb muscles following chronic stroke in rats despite persistent motor impairment

Ross, S. A.; Dorscher, S. N.; Leonard, T. R.; Seerattan, R. A.; Corbett, D.; Herzog, W.

2026-09-15 physiology 10.64898/2026.09.09.750457 medRxiv
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Stroke causes motor impairments that are commonly attributed to altered neural control, but chronic changes in neural activation and muscle use may also influence skeletal muscle structure. This study examined whether chronic stroke alters sarcomere length and dispersion, fascicle length, or serial sarcomere number in adult skeletal muscle. Twenty-four female Sprague-Dawley rats underwent photothrombotic stroke or sham surgery. Limb-specific motor impairment was assessed longitudinally using a beam traversal task. At 4.5 months post-surgery, the lateral gastrocnemius and extensor digitorum longus muscles were harvested from paretic and non-paretic limbs. We measured fascicle length directly from isolated fascicle bundles and quantified sarcomere length and dispersion using laser diffraction. Stroke animals exhibited persistent impairment of the paretic limb during beam traversal with elevated misstep rates. Despite this persistent motor impairment, sarcomere length and dispersion did not differ between stroke and sham animals or between limbs. Fascicle length and serial sarcomere number were greater in stroke than sham animals, but these differences were not limb-specific and were therefore unlikely to reflect stroke-related changes. Fascicle length, sarcomere length and dispersion, and serial sarcomere number differed between the lateral gastrocnemius and extensor digitorum longus, consistent with differences in architecture or relative length at the selected joint angles. These findings indicate that persistent neural impairment following adult-onset stroke does not necessarily result in substantial changes in sarcomere length or sarcomeres in series. Instead, sarcomere changes may depend on additional factors, including the timing of neural injury relative to growth and the mechanical environment experienced by the muscle.

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Acute caffeine ingestion differentially alters motor unit behaviour during submaximal and fatiguing contractions

Guo, Y.; Inns, T. B.; Sun, V.; Jones, E. J.; Phillips, B. E.; Atherton, P.; Piasecki, M.

2026-09-21 physiology 10.64898/2026.09.15.751700 medRxiv
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Background: Caffeine is widely used as an ergogenic aid, yet its effect on neuromuscular function remains heterogeneous across exercise conditions. Although caffeine is known to enhance central nervous system excitability through adenosine receptor antagonism, the extent to which these effects modify spinal motor output remains unclear. Therefore, the present study aimed to characterise acute caffeine-induced alterations in neuromuscular properties during submaximal and sustained fatiguing contractions of the knee extensors. Methods: Seventeen healthy adults completed a randomised, placebo-controlled crossover study (3 mg/kg caffeine). Circulating serum caffeine concentrations were periodically quantified, while motor unit (MU) discharge behaviour, and delta F were derived from high-density surface electromyography. Statistical significance was set at p = 0.05. Results: No intervention effects were observed for MVC, force steadiness, or time to task failure (all p > 0.05). During graded contractions, vastus lateralis MU discharge rate was higher under caffeine (p < 0.001), and discharge variability was lower (p = 0.016). Recruitment and derecruitment thresholds were significantly greater under caffeine at 50% MVC (both p < 0.012), whereas paired MU analyses of delta F was unchanged (p = 0.083). During sustained contractions, caffeine altered fatigue-related trajectories of both MU discharge and discharge variability (intervention * phase interaction, p < 0.011). Conclusions: Acute caffeine ingestion alters motor unit behaviour without enhancing maximal force or fatigue resistance. These effects vary with contraction intensity and fatigue state but are not accompanied by a detectable change in discharge rate hysteresis in the vastus lateralis.

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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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Evaluating home-cage-activity metrics for detecting postprocedural pain in a plantar incision mouse model

Malmberg, M. E.; Bertelsen, T.; Bollen, P.; Abelson, K.; Hestehave, S.; Kalliokoski, O.

2026-09-25 animal behavior and cognition 10.64898/2026.09.23.753854 medRxiv
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Detection of postoperative pain in mice is challenging, and there is a need for unbiased, automated methods. Home-cage monitoring systems are promising, but their ability to detect mild pain remains unclear. We evaluated whether home-cage activity measures can be used to detect pain-related changes in a plantar incision model of postoperative pain. First, we confirmed the presence of local hypersensitivity using von Frey filaments on 48 C57BL/6JRj mice (24 males, 24 females). Subsequently, we pair-housed 64 mice (32 males, 32 females) and allocated them to receive either a 4 mm plantar incision on the hind paw under anaesthesia, or anaesthesia alone. Baseline locomotion and voluntary wheel-running activity were recorded over five days, followed by four days of postprocedural monitoring in the home cages. Both procedure groups (incision and anaesthesia-only) showed reduced locomotion and running wheel activity relative to baseline. However, activity measures did not differ between incised and anaesthesia-only mice, and we detected no sex-related effects. Under these conditions, home cage activity measures did not reliably discriminate pain-related behavioural changes in the model, despite the model showing local mechanical hypersensitivity in the von Frey test. Together, these findings indicate that, given the mild and localised nature of the plantar incision mouse model, commonly used home-cage metrics cannot yet reliably detect subtle pain-related behavioural changes.

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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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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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Constitutive Stim1L Deletion Alters Store-Operated Calcium Entry Kinetics But Does Not Perturb The Development And Function Of Mouse Skeletal Muscle

Dopont, O.; Lopez, G.; Lilliu, E.; Castets, P.; Koenig, X.; Frieden, M.; Koenig, S.

2026-10-04 physiology 10.64898/2026.09.28.755229 medRxiv
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Store-operated calcium entry (SOCE) is a ubiquitous calcium (Ca2+) signalling mechanism that replenishes endoplasmic and sarcoplasmic reticulum Ca2+ stores. We previously identified STIM1L, a skeletal muscle-enriched STIM1 splice variant that enables rapid SOCE activation in human myotubes. To determine its physiological role in vivo, we generated a constitutive knockout mouse model that selectively abolishes STIM1L expression while preserving the canonical STIM1 isoform. Stim1l-KO mice developed normally and exhibited no overt abnormalities, but both sexes showed reduced voluntary wheel-running activity, suggesting neuromuscular perturbation. Skeletal muscle deprived of STIM1L did not show any histological alterations or changes in fibre- type and size. Likewise, force-frequency relationships and fatigue resistance measured ex vivo in isolated extensor digitorum longus and soleus muscles were indistinguishable from control muscles. This lack of difference may be explained by the increased expression of STIM1 in several skeletal muscles and suggests that changes in the voluntary running activity of Stim1l-KO mice may arise from STIM1L loss in non-muscular tissues, including the central nervous system. Notwithstanding, primary myotubes derived from Stim1l-KO mice displayed a marked delay in SOCE activation kinetics, whereas SOCE amplitude remained comparable to controls. This was consistent with a compensatory STIM1 upregulation maintaining overall Ca2+ entry capacity. Interestingly, electrically evoked Ca2+ transients in intact Stim1l-KO flexor digitorum brevis fibres exhibited significantly faster decay kinetics than controls. This revealed another role of STIM1L in Ca2+ handling in skeletal muscle that appears independent of its contribution to SOCE activation. Together, these findings establish STIM1L as a regulator of SOCE activation kinetics and indicate an additional role in myofibre Ca2+ clearance, while suggesting that compensatory upregulation of canonical STIM1 may preserve muscle structure and contractile function in its absence in mice.

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Arm locomotor behaviour affects motor unit discharge characteristics in the stationary leg

Nazaroff, B. M.; Mitchell, E. R.; Pearcey, G.

2026-08-21 neuroscience 10.64898/2026.08.17.745355 medRxiv
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Persistent inward currents (PICs), which are facilitated by monoaminergic inputs such as serotonin (5-HT), amplify synaptic drive and strongly influence motoneuron excitability. Although rhythmic locomotor activity increases serotonergic drive in animal models, its effects on intrinsic motoneuron properties in humans remain unclear. We examined whether rhythmic arm cycling alters motoneuron excitability of the non-exercising tibialis anterior during submaximal contractions. Twelve healthy adults (8 males, 4 females) performed triangular isometric dorsiflexion contractions at 25% and 50% MVC under four conditions: resting arm (CONTROL), finger tapping (TAP), arm cycling at 50-60 RPM (LOW), and arm cycling at 80-90 RPM (HIGH). Motor unit activity was identified from high-density surface electromyography that was decomposed into spike trains. Recruitment thresholds of identified and tracked motor units were consistent across conditions, but {Delta}F (i.e., an estimate of the PIC-related contributions to motor unit discharge) decreased during high-cadence arm cycling at stronger contraction intensities, which may reflect either reduced neuromodulation and/or increased or altered patterns of inhibition. In contrast, ascending discharge rate modulation deviated from linearity to a greater extent (i.e., brace height was larger) during both low- and high-cadence cycling, indicating greater neuromodulatory influence on the ascending discharge rate pattern. Self-sustained discharge was also elevated during cycling tasks, reflecting prolonged motor unit discharge. Taken together, these findings suggest that rhythmic activity of the arms modulates the discharge characteristics of motoneuron pools in the legs via unique combinations of excitatory, neuromodulatory and inhibitory inputs, which advances our understanding on the mechanisms of interlimb neural coupling.

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Vocal fold injury alters acoustic phenotype despite preserved vocal activity

Hogan, S.; Lee, J. K.; Riede, T.

2026-10-06 physiology 10.64898/2026.09.29.755416 medRxiv
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Vocal communication depends on the biomechanical integrity of the vocal folds, yet how impairment alters vocal behavior remains poorly understood. We used the California mouse (Peromyscus californicus), a highly vocal species that produces songs through airflow-induced vocal fold vibration, to experimentally examine how defined vocal fold injury alters vocal production. Longitudinal recordings were combined with histological assessment to track changes in vocal function after impairment. Injury produced acute edema of the lamina propria and thyroarytenoid muscle. Despite stable levels of vocal activity, the vocal phenotype shifted characteristically following injury. Thus, vocal behavior can persist despite substantial alteration of the biomechanical tissues underlying sound production, demonstrating that maintenance of behavioral output does not necessarily indicate preservation of the physiological system that generates it. More broadly, these findings establish an experimental link between vocal fold injury and vocal phenotype and provide a framework for understanding how tissue damage and remodeling can reshape acoustic communication even when vocal behavior is maintained. Because repeated vocalization can impose substantial mechanical demands on vocal folds, this framework may have broad relevance for understanding how vocal use, injury, and tissue remodeling interact to shape vocal communication.

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Sequential VEGF-A165 plasmid and AAV-follistatin gene therapy enhances muscle hypertrophy and capillarisation in C57BL/6 mice

Vakhrusheva, A.; Nedorubov, A.; Leshko, V.; Morgunov, I.

2026-08-28 physiology 10.64898/2026.08.26.747237 medRxiv
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Introduction. Skeletal muscle loss in sarcopenia and neuromuscular disorders remains a major unmet medical need. AAV9-delivered follistatin (FST), a myostatin/activin antagonist, induces muscle hypertrophy; however, fibre growth without adequate vascular adaptation may limit therapeutic efficacy. We evaluated whether co-administration of a VEGF-A165 plasmid enhances the hypertrophic and angiogenic effects of intramuscular AAV-FST gene transfer in C57BL/6 mice. Methods. Thirty-six C57BL/6 mice (18 males, 18 females) were assigned to PBS vehicle (n=10), AAV-FST (1 x 10^11 vg; n=10), VEGF plasmid (100 ug; n=6), or combination treatment (VEGF plus AAV-FST; n=10). The contralateral hindlimb served as an internal control. Endpoints at Day 115 included hindlimb muscle mass ratio (R/L), transgene expression, FST protein levels, muscle fibre morphometry, capillary density, and safety assessments. Results. Combination therapy produced the highest R/L ratio (1.176 +/- 0.091; p=0.004; d=2.04), whereas AAV-FST alone showed a borderline effect (R/L=1.113; p=0.050). Compared with AAV-FST monotherapy, combination treatment increased muscle FST mRNA approximately 2.1-fold, protein levels approximately 2.0-fold, and the muscle-to-liver expression ratio 2.6-fold. It also induced larger muscle fibres and doubled CD31+ vessel counts versus AAV-FST alone, indicating simultaneous hypertrophy and angiogenesis. No adverse haematological, biochemical, or histopathological findings were observed. Discussion. Combined AAV-FST and VEGF therapy enhanced local muscle hypertrophy, increased capillary density, and improved the muscle-to-liver transgene expression profile compared with AAV-FST monotherapy. The regimen was well tolerated and supports further evaluation of angiogenic preconditioning as a strategy to improve muscle-directed gene therapy for muscle-wasting disorders.

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

Connelly, C. D.; Folland, J. P.; Piasecki, M.; Skarabot, J.

2026-09-22 physiology 10.64898/2026.09.15.751873 medRxiv
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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[&ge;]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.

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Quantitative Ultrasound Analysis of Gas Embolic Disease in Bycaught Sea Turtles

Eltz, K.; Crespo, J. L.; Azarang, A.; Gonzalez, E. P.; Garcia, D.; Fahlman, A.; Papadopoulou, V.

2026-07-30 physiology 10.64898/2026.07.27.740119 medRxiv
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ObjectivesBycatch-related decompression after forced submersion can result in severe gas embolic disease in sea turtles. This work used qualitative and quantitative ultrasound analyses, including gas grading, brightness analysis, and texture feature extraction, to investigate organ-specific gas burden and temporal evolution in the hearts, kidneys, and livers of bycaught sea turtles. Materials and MethodsUltrasound imaging of the hearts, kidneys, and livers of bycaught turtles was performed as part of veterinary evaluation either onboard fishing vessels immediately after surfacing (boat group, n=47) or after longer periods at shore-based facilities (shore group, n=30). Gas burden in each ultrasound scan was graded on an ordinal scale from 0 (no gas) to 5 (gas completely shadowing organ anatomy). Temporal differences in gas burden were compared between the shore and boat groups. Quantitative brightness and texture features were extracted from all organs, including contrast, correlation, homogeneity, and energy from liver and kidney data. A multivariate logistic regression model with leave-one-out cross-validation was conducted, with shore versus boat as a binary outcome (surrogate of post-surfacing decompression state) and ultrasound texture metrics as independent variables. ResultsMedian grades from the first ultrasound scan were significantly higher in the boat group than in the shore group for the liver, kidney, and heart (3, 3, and 3 vs 1, 1, and 0, respectively). This pattern coincided with a difference in the mean duration until the first scan which was conducted being 54 min for the onboard studies vs 330 minutes in the shore group. Mean pixel brightness within cardiac and liver regions of interest increased with rising bubble grade before decreasing at the highest grades, consistent with acoustic shadowing at severe gas burden. Texture features demonstrated significant organ-specific changes with increasing gas burden, and the regression models achieved areas under the receiver operating characteristic curve of 0.92 for liver texture features and 0.83 for kidney texture features. ConclusionsThese findings demonstrate organ-specific differences in gas evolution over time. Quantitative ultrasound features were associated with gas burden and post-surfacing interval in bycaught sea turtles. These findings support the feasibility of quantitative ultrasound biomarkers for assessment of decompression-related gas burden.

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Thoracoabdominal pressure transmission during prone and supine cardiopulmonary resuscitation in fresh-frozen human cadavers

Smith, Z.; Lust, R.; Falyar, C.; Swanson, M.; Akintade, B.; Bolin, L.

2026-09-29 physiology 10.64898/2026.09.22.753658 medRxiv
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Background: Prone cardiopulmonary resuscitation (CPR) may be necessary when turning a prone patient supine would delay chest compressions. Although prone compressions can generate arterial pressures comparable with or greater than supine CPR, the pathway of pressure transmission is uncertain. We examined synchronized intrathoracic, intra-abdominal, and central arterial pressures in both supine and prone positions. Methods: Two thawed fresh-frozen adult cadavers underwent three, 2-minute mechanical CPR trials per position in a counterbalanced crossover sequence. Solid-state catheters recorded pleural, peritoneal, and central arterial pressures simultaneously. Trial-level outcomes included peak pressure, mean pressure, pressure-time area, and the mean peritoneal-to-pleural pressure gradient. Exploratory fixed-effects models included position, cadaver, and their interaction. Results: Prone CPR increased peak intrathoracic pressure by 7.04 mmHg, peak intra-abdominal pressure by 21.69 mmHg, and peak arterial pressure by 15.40 mmHg. Mean intra-abdominal and arterial pressures increased by 16.22 and 9.90 mmHg, respectively. The mean peritoneal-to-pleural gradient reversed direction from -8.46 mmHg supine to 4.85 mmHg prone. Intrathoracic pressure-time area increased 3.4-fold, from 1.62 to 5.46 mmHg{middle dot}s, and arterial pressure-time area increased 2.2-fold, from 2.96 to 6.42 mmHg{middle dot}s. Conclusions: Compared to supine, prone mechanical CPR generated higher arterial pressures and reversed the pressure relationship across the thoracoabdominal boundary in both cadavers. Higher abdominal pressure coincided with a larger intrathoracic pressure-time area, a pattern compatible with reduced caudal pressure dissipation.

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Sport expertise and motor imagery abilities shape sensorimotor rhythm modulations during visualisation tasks: Implications for neurofeedback-based cognitive training in athletes

Izac, M.; Pierrieau, E.; Rossignol, E.; Grechukhin, N.; Coudroy, E.; Pillette, L.; N'Kaoua, B.; Jeunet-Kelway, C.

2026-09-01 neuroscience 10.64898/2026.08.26.747187 medRxiv
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Kinaesthetic motor imagery (kMI) is widely used in sport to enhance motor performance by engaging cortical sensorimotor networks. Neurofeedback may further support kMI, but the optimal neural target to reinforce remains unclear. Maximal sensorimotor event-related desynchronisation (SMR-ERD) represents a relevant target as it may index sensorimotor cortex engagement, yet sport expertise has been associated with reduced SMR-ERD, potentially reflecting neural efficiency. The optimal neurofeedback target may therefore depend on sport expertise, movement expertise, and individual kMI ability. This study examined how these factors influence sensorimotor activity during kMI. We compared 17 basketball players (Experts) and 16 individuals without formal basketball training (Novices). kMI ability and frequency of use were assessed using questionnaires, while SMR-ERD was quantified using electroencephalography (EEG) during kMI. Participants imagined either a basketball-specific movement (Free throw), for which only Experts had extensive experience, or a generic movement (Box lifting), familiar to both groups. Experts reported greater kMI ability and more frequent kMI use than Novices. Only Experts exhibited significant and sustained SMR-ERD during kMI. Moreover, SMR-ERD was stronger in Experts than Novices specifically during Free throw kMI, corresponding to their movement of expertise. Nonetheless, within the Expert group, higher kMI ability was associated with reduced SMR-ERD. These findings suggest that sport expertise initially enhances voluntary recruitment of sensorimotor networks during kMI, whereas greater kMI ability may subsequently promote neural efficiency, resulting in reduced overall sensorimotor cortical activation. These results highlight the need to tailor kMI-based neurofeedback training to users' sport expertise and kMI ability levels.

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Estimates of persistent inward currents in human spinal motor neurons: non-linear and sex-dependent trajectories from young to very old age

Chatain, C.; Hamard, R.; Cattagni, T.; Roty, R.; Lepers, R.; Rozand, V.

2026-09-29 physiology 10.64898/2026.09.24.754101 medRxiv
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The contribution of persistent inward currents (PICs) to spinal motor neurons discharge rate is lower in old compared to young adults. However, whether this difference further progresses at very old age ([&ge;]80 years) and differs between males and females remains unknown. Thirty young (26 {+/-} 4 years, 15 females), thirty old (72 {+/-} 5 years, 15 females) and twenty-nine very old adults (85 {+/-} 3 years, 15 females) performed isometric dorsiflexion ramp contractions at 20% of maximal voluntary torque. Individual motor unit spike trains were identified from decomposed high-density surface electromyograms of the tibialis anterior. The paired motor unit technique was used to estimate the prolongation effect of PICs ({Delta}F and normalized {Delta}F), and the quasi-geometric approach to estimate neuromodulatory (brace height) and inhibitory pattern (attenuation slope) contributions. {Delta}F was lower in old and very old adults than in young adults, with no difference between old and very old adults regardless of sex. Compared with young adults, normalized {Delta}F was lower in both old and very old males, whereas in females it is only lower in the very old group. Brace height and attenuation slope did not differ across ages or sexes. These findings indicate that age-related changes in spinal motor neuron excitability are established by the seventh decade and do not progress further in healthy active very old adults, following a nonlinear trajectory that may differ between males and females. The absence of age-related differences in the neuromodulatory index does not support a lower monoaminergic drive in older adults.

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Complementing Behavioral Weight Loss with Breath-based Yoga: A Proof-of-Concept and Initial Feasibility Study

Purcell, S. A.; Dallaghan, P.; Catenacci, V.; Bing, K.; Falkenhain, K.; Caldwell, A. E.

2026-07-31 endocrinology 10.64898/2026.07.27.26358493 medRxiv
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Background: Yoga may support changes in dietary intake and/or physical activity levels, supporting sustainable weight loss. However, previous research has focused on yoga postures (asanas) rather than breathing practices (pranayama). This study used the proof-of-concept stage in the ORBIT model to evaluate feasibility, acceptability, and preliminary efficacy of a breath-based yoga program integrated within a behavioral weight loss (BWL) intervention. Methods: Fifteen participants with overweight or obesity (BMI: 31.3 +/- 4.3, 80% female) were enrolled in a 16-week, single-arm, group-based BWL intervention which included four breath-based yoga sessions/week, individualized daily goals for energy intake reduction, and progressive aerobic exercise recommendations. Primary outcomes included prespecified benchmarks enrollment, retention, adherence, and acceptability. Secondary outcomes included changes in body weight and composition, metabolic health indices (e.g., blood pressure, fasting glucose, abdominal obesity), physical activity, appetite, and dietary intake. Results: Mean percent weight loss was 6.5 +/- 6.0%, exceeding the pre-defined proof-of-concept benchmark. Recruitment and adherence exceeded established benchmarks, with mean in-class attendance of 84.1 +/- 14.6% and adherence to the prescribed duration of at-home yoga sessions averaging 85.5 +/- 38.4%. However, retention was lower than the pre-specified benchmark (73% vs 80%). Positive changes were observed in waist circumference, blood pressure, and appetite traits. Self-reported satisfaction with the program and outcomes were acceptable (mean ratings >6/10). Conclusions: A BWL with a breath-based, low-intensity yoga can lead to acceptable weight loss with potential benefits in key behavioral and metabolic health indices. Recruitment, high adherence, and satisfaction demonstrated feasibility.

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The Plateau Hemoglobin Paradox: Reversed Effect of Hemoglobin on Surgical Outcomes by Oxygen Saturation Strata at High Altitude

Dang, Z.; Dan, J.; Su, W.; Ren, G.; Wang, Z.; Ma, Y.; Li, S.; Ji, D.; Li, L.; Gao, J.

2026-08-23 surgery 10.64898/2026.08.19.26360786 medRxiv
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Background: Hemoglobin (Hb) elevation is the hallmark of high-altitude adaptation, yet its effect on surgical outcomes may depend on arterial oxygen saturation (SpO2)--previously uninvestigated. Objectives: To explore whether preoperative Hb effect on postoperative length of stay (LOS) after laparoscopic cholecystectomy (LC) reverses across SpO2 strata. Methods: Retrospective single-center cohort of 612 adults undergoing elective LC (2018-2023) at Qinghai Red Cross Hospital, Xining, China (2260 m). Exposure: preoperative Hb (82-233 g/L) and SpO2 (86%-99%), stratified as low (<93%), mid (93%-95%), high (>=96%). Primary analysis: multivariable linear regression with Hb x SpO2 interaction, adjusted for BMI, age, sex, season. Results: Among 612 patients (65.8% female; mean age 43.5 [11.9] years; mean Hb 151.4 [20.7] g/L; mean SpO2 94.6% [2.3%]), the Hb x SpO2 interaction was significant (beta = -0.0095; P = .009). Hb effect reversed: in SpO2 >=93%, each 1 g/L Hb prolonged LOS by 0.003 days (P = .079); in SpO2 <93%, each 1 g/L reduced LOS by 0.006 days. In mid-SpO2 stratum (n = 251), Hb >=180 g/L had longer LOS (1.88 vs 1.62 days; P = .001; d = 0.54). Five computational robustness analyses confirmed the interaction (leave-one-out: 100% P < .05 across 612 iterations). Conclusions: In this exploratory cohort, we observed an SpO2-dependent reversal of the Hb effect on postoperative LOS, designated the "Plateau Hemoglobin Paradox." Given single-center design and achieved power of 0.754, findings require replication. If replicated, this pattern may inform future perioperative risk stratification at high altitude.