Plantar Flexion Torque Research Articles

Maintained volitional activation of the muscle alters the cortical processing of proprioceptive afference from the ankle joint

Cortical proprioceptive processing of intermittent, passive movements can be assessed by extracting evoked and induced electroencephalographic (EEG) responses to somatosensory stimuli. Although the existent prior research on somatosensory stimulations, it remains unknown to what extent ongoing volitional muscle activation modulates the proprioceptive cortical processing of passive ankle-joint rotations.Twenty-five healthy volunteers (28.8 ± 7 yr, 14 males) underwent a total of 100 right ankle-joint passive rotations (4° dorsiflexions, 4 ± 0.25 s inter-stimulus interval, 30°/s peak angular velocity) evoked by a movement actuator during passive condition with relaxed ankle and active condition with a constant plantarflexion torque of 5 ± 2.5 Nm. Simultaneously, EEG, electromyographic (EMG) and kinematic signals were collected. Spatiotemporal features of evoked and induced EEG responses to the stimuli were extracted to estimate the modulation of the cortical proprioceptive processing between the active and passive conditions.Proprioceptive stimuli during the active condition elicited robustly ∼26 % larger evoked response and ∼38 % larger beta suppression amplitudes, but ∼42 % weaker beta rebound amplitude over the primary sensorimotor cortex than the passive condition, with no differences in terms of response latencies.These findings indicate that the active volitional motor task during naturalistic proprioceptive stimulation of the ankle joint enhances related cortical activation and reduces related cortical inhibition with respect to the passive condition. Possible factors explaining these results include mechanisms occurring at several levels of the proprioceptive processing from the peripheral muscle (i.e. mechanical, muscle spindle status, etc.) to the different central (i.e. spinal, sub-cortical and cortical) levels.

Torque-ratio-adjustable ankle-foot exoskeleton for resisting perturbation in forward direction within fan-shaped region of pelvis horizontal plane.

Introduction: The ankle-foot exoskeleton has been demonstrated to help users resist anterior perturbation in the horizontal pelvis plane. However, its effects on perturbations in other directions remain unclear. This paper focuses on how the ankle-foot exoskeleton helps people resist perturbations coming from forward directions within the fan-shaped region in the pelvis horizontal plane. Methods: Firstly, we proposed and validated a hypothesis that the human torque ratio of inversion to plantar flexion torque would change with the perturbation directions of anterior (dir0) and 45° deviating from anterior to left (dir45). Subsequently, based on the regulation demand, we developed an ankle-foot exoskeleton that can adjust the torque ratio delivered to the human body by controlling the forces on two cross-arranged cables. Finally, we evaluated and compared the assistance performance of three powered assistive modes (NM, medBD, and latBD) with the unpowered one (UN) by setting different force pairs in two cables. Results: The results showed that, with the assistance, the margin of stability was increased and the standard deviations of ankle-foot segmental movements were decreased. Meanwhile, the biological inversion torque has a significant difference among the three assistive modes. Compared to the UN, the latBD was shown to reduce the biological inversion torque by 15.8 and 13.7 in response to the dir0 and dir45 perturbations, respectively, while the reductions for the NM and medBD were smaller. It was also observed that the torque ratios, generated by the human and the exoskeleton in latBD mode, differed by about 0.1 under dir0 and 0.08 under dir45, while the physiologically similarity of the exoskeleton torque ratio in NM and medBD modes were smaller. Based on the above results, we found that the more physiologically similar the exoskeleton torque ratio, the better the assistive performance. Discussion: The findings demonstrated that the torque-ratio-adjustable exoskeleton could support human resistance to perturbations coming from forward directions within a fan-shaped region in the pelvis horizontal plane and indicated that the exoskeleton's torque ratio should be carefully modulated to match the ratio of the human under various environmental conditions for better assistive performance.

Combining Neuromodulation Strategies in Spinal Cord Injury Gait Rehabilitation: A Proof of Concept, Randomized, Crossover Trial

ObjectivesTo evaluate if acute intermittent hypoxia (AIH) coupled with transcutaneous spinal cord stimulation (tSCS) enhances task-specific training and leads to superior and more sustained gait improvements as compared with each of these strategies used in isolation in persons with chronic, incomplete spinal cord injury. DesignProof of concept, randomized crossover trial. SettingOutpatient, rehabilitation hospital. InterventionsTen participants completed 3 intervention arms: (1) AIH, tSCS, and gait training (AIH + tSCS); (2) tSCS plus gait training (SHAM AIH + tSCS); and (3) gait training alone (SHAM + SHAM). Each arm consisted of 5 consecutive days of intervention with a minimum of a 4-week washout between arms. The order of arms was randomized. The study took place from December 3, 2020, to January 4, 2023. Main Outcome Measures10-meter walk test at self-selected velocity (SSV) and fast velocity, 6-minute walk test, timed Up and Go (TUG) and secondary outcome measures included isometric ankle plantarflexion and dorsiflexion torque ResultsTUG improvements were 3.44 seconds (95% CI: 1.24-5.65) significantly greater in the AIH + tSCS arm than the SHAM AIH + tSCS arm at post-intervention (POST), and 3.31 seconds (95% CI: 1.03-5.58) greater than the SHAM + SHAM arm at 1-week follow up (1WK). SSV was 0.08 m/s (95% CI: 0.02-0.14) significantly greater following the AIH + tSCS arm than the SHAM AIH + tSCS at POST. Although not significant, the AIH + tSCS arm also demonstrated the greatest average improvements compared with the other 2 arms at POST and 1WK for the 6-minute walk test, fast velocity, and ankle plantarflexion torque. ConclusionsThis pilot study is the first to demonstrate that combining these 3 neuromodulation strategies leads to superior improvements in the TUG and SSV for individuals with chronic incomplete spinal cord injury and warrants further investigation.

Motoneuron persistent inward current contribution to increased torque responses to wide-pulse high-frequency neuromuscular electrical stimulation

PurposeTo assess the effect of a remote handgrip contraction during wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) on the magnitude of extra torque, progressive increase in torque during stimulation, and estimates of the persistent inward current (PIC) contribution to motoneuron firing in the plantar flexors.MethodsTen participants performed triangular shaped contractions to 20% of maximal plantar flexion torque before and after WPHF NMES with and without a handgrip contraction, and control conditions. Extra torque, the relative difference between the initial and final torque during stimulation, and sustained electromyographic (EMG) activity were assessed. High-density EMG was recorded during triangular shaped contractions to calculate ∆F, an estimate of PIC contribution to motoneuron firing, and its variation before vs after the intervention referred to as ∆F change score.ResultsWhile extra torque was not significantly increased with remote contraction (WPHF + remote) vs WPHF (+ 37 ± 63%, p = 0.112), sustained EMG activity was higher in this condition than WPHF (+ 3.9 ± 4.3% MVC EMG, p = 0.017). Moreover, ∆F was greater (+ 0.35 ± 0.30 Hz) with WPHF + remote than control (+ 0.03 ± 0.1 Hz, p = 0.028). A positive correlation was found between ∆F change score and extra torque in the WPHF + remote (r = 0.862, p = 0.006).DiscussionThe findings suggest that the addition of remote muscle contraction to WPHF NMES enhances the central contribution to torque production, which may be related to an increased PIC contribution to motoneuron firing. Gaining a better understanding of these mechanisms should enable NMES intervention optimization in clinical and rehabilitation settings, improving neuromuscular function in clinical populations.

The Impact of Induced Acceleration Perturbations in Selected Phases of the Gait Cycle on Kinematic and Kinetic Parameters

Background: The prevalence of falls among the older population underscores the imperative of comprehending human adaptations to gait perturbations. Dual-belt treadmills offer a controlled setting for such investigations. The purpose of this study was to examine the effect of the acceleration of one belt of the treadmill during three different phases of the gait cycle on kinematic and kinetic parameters and relate these changes to unperturbed gait. Methods: Twenty-one healthy young females walked on a treadmill in a virtual environment, in which five unexpected perturbations were applied to the left belt at the Initial Contact (IC), Mid Stance (MS), and Pre-Swing (PS) phase of the gait cycle. Data from the undisturbed gait and the first disturbance of each trial were extracted for analysis. Results: All perturbations significantly affected the gait pattern, mainly by decreasing the knee extension angle. The perturbation in the IC phase had the most significant effect, resulting in a 248.48% increase in knee flexion torque. The perturbation in the MS phase mainly affected plantar flexion torque, increasing it by 118.18%, while perturbation in the PS phase primarily increased the hip extension torque by 73.02%. Conclusions: The presence of perturbations in the IC and PS phases caused the most aggressive and significant changes in gait parameters.

A surgical technique for individual control of the muscles of the rabbit lower hindlimb.

Little is known regarding the precise muscle, bone and joint actions resulting from individual and simultaneous muscle activation(s) of the lower limb. An in situ experimental approach is described herein to control the muscles of the rabbit lower hindlimb, including the medial and lateral gastrocnemius, soleus, plantaris and tibialis anterior. The muscles were stimulated using nerve-cuff electrodes placed around the innervating nerves of each muscle. Animals were fixed in a stereotactic frame with the ankle angle set at 90deg. To demonstrate the efficacy of the experimental technique, isometric plantarflexion torque was measured at the 90deg ankle joint angle at a stimulation frequency of 100, 60 and 30 Hz. Individual muscle torque and the torque produced during simultaneous activation of all plantarflexor muscles are presented for four animals. These results demonstrate that the experimental approach was reliable, with insignificant variation in torque between repeated contractions. The experimental approach described herein provides the potential for measuring a diverse array of muscle properties, which is important to improve our understanding of musculoskeletal biomechanics.

The Effects of 5 Minutes of Static Stretching on Joint Flexibility and Muscle Strength Are Comparable Between Ballet Dancers and Non-Dancers.

Introduction: Ballet dancers have a special morphology, such as a large muscle thickness that affects passive torque. Ballet dancers also possess specialized mechanical, and neural properties of muscles and tendons. These characteristics may produce different static stretching effects than non-dancers. Therefore, this study aimed to determine the differences in the effects of static stretching on joint range of motion, passive torque, and muscle strength between ballet dancers and non-dancers. Methods: This study included 13 ballet dancers and 13 college students. The muscle and tendon thicknesses were assessed using ultrasonography. In the right lower extremity, torque-angle data and muscle-tendon junction displacement measurements were obtained during isokinetic passive dorsiflexion before and after a 5-minute static stretch against the right plantar flexors. The relative stretching intensity was calculated by dividing the stretching angle by the maximal dorsiflexion angle pre-stretch. Additionally, the isometric maximal voluntary plantar flexion torque on the left ankle was measured before and after 5 minutes of static stretching against the left plantar flexors. Results: Ballet dancers had significantly greater muscle thickness than non-dancers (22.4 ± 2.2 vs 18.1 ± 1.7 mm), whereas no significant difference was observed in the Achilles tendon thickness. No significant difference was observed in the stretching angle; however, the relative stretching intensity was higher in the control group (65.9 ± 19.8 vs 127.5 ± 63.8%). Static stretching increased the maximal dorsiflexion angle (dancer: 30.4° ± 9.6° to 33.9° ± 9.5°, non-dancer: 18.4° ± 8.6° to 20.5° ± 9.5°) and maximal passive torque in both groups, whereas the maximal isometric plantar flexion torque and submaximal passive torque decreased. However, no significant differences were observed in the changes between the groups. Conclusion: These results indicate that despite having a lower relative stretching intensity, ballet dancers experienced similar changes as non-dancers after 5 minutes of static stretching.

Effects of 12-week gait retraining on plantar flexion torque, architecture, and behavior of the medial gastrocnemius in vivo.

This study aims to explore the effects of 12-week gait retraining (GR) on plantar flexion torque, architecture, and behavior of the medial gastrocnemius (MG) during maximal voluntary isometric contraction (MVIC). Thirty healthy male rearfoot strikers were randomly assigned to the GR group (n = 15) and the control (CON) group (n = 15). The GR group was instructed to wear minimalist shoes and run with a forefoot strike pattern for the 12-week GR (3 times per week), whereas the CON group wore their own running shoes and ran with their original foot strike pattern. Participants were required to share screenshots of running tracks each time to ensure training supervision. The architecture and behavior of MG, as well as ankle torque data, were collected before and after the intervention. The architecture of MG, including fascicle length (FL), pennation angle, and muscle thickness, was obtained by measuring muscle morphology at rest using an ultrasound device. Ankle torque data during plantar flexion MVIC were obtained using a dynamometer, from which peak torque and early rate of torque development (RTD50) were calculated. The fascicle behavior of MG was simultaneously captured using an ultrasound device to calculate fascicle shortening, fascicle rotation, and maximal fascicle shortening velocity (Vmax). After 12-week GR, 1) the RTD50 increased significantly in the GR group (p = 0.038), 2) normalized FL increased significantly in the GR group (p = 0.003), and 3) Vmax increased significantly in the GR group (p = 0.018). Compared to running training, GR significantly enhanced the rapid strength development capacity and contraction velocity of the MG. This indicates the potential of GR as a strategy to improve muscle function and mechanical efficiency, particularly in enhancing the ability of MG to generate and transmit force as well as the rapid contraction capability. Further research is necessary to explore the effects of GR on MG behavior during running in vivo.

Strength and Functional Outcomes Following Achilles Tendon Reconstruction With Hamstring Tendon Autograft Augmentation.

The proposed advantages of hamstring autograft reconstruction when compared to alternative procedures, such as flexor hallucis longus (FHL) transfer, V-Y lengthening, and allograft reconstruction, are improved healing and reproduction of normal tendon biomechanics and reduced morbidity within the foot and ankle. In this study, we examined the effect of Achilles tendon reconstruction using hamstring autografts on strength and functional outcomes. Patients who underwent Achilles repair with a hamstring autograft for insertional or midsubstance tendinopathy, delayed diagnosis of rupture, or infection after primary repair were evaluated for inclusion. Forty-six patients were identified; 12 further augmented with an FHL transfer are included in the analysis. Isokinetic testing was completed with a Biodex dynamometer under supervision of a physical therapist masked to surgical side. Pre- and postoperative Foot and Ankle Outcome Scores (FAOS, before March 2016) or Patient-Reported Outcomes Measurement Information System (PROMIS, after March 2016) surveys were collected. For knee flexion, peak torque was not significantly different when comparing operative and nonoperative sides at 180 degrees/second (45.38 Nm vs 45.96 Nm; P = .69) nor at 300 degrees/second (44.2 Nm vs 47.02 Nm; P = .069). Knee extension absolute peak torque was only found to be significantly weaker on the operative side at the faster testing (75.5 Nm vs 79.56 Nm; P < .05). Peak ankle plantarflexion torque was significantly weaker on the operative side at both the slower speed (60 degrees/second: 39.9 Nm vs 48.76 Nm; P < .005) and the faster speed (120 degrees/second: 31.3 Nm vs 40.7 Nm; P < .001). Average power for ankle plantarflexion did not differ significantly from the operative side to the nonoperative side in the slower test (26.46 W vs 27.48 W; P = .60) but did significantly differ on the faster test (32.13 W vs 37.63 W; P = .041). At an average of 19.9 months postoperation, all physical function and pain-related patient-reported outcome scores showed clinically and statistically significant improvement. Achilles reconstruction with a hamstring autograft ± FHL transfer allowed patients with severe Achilles pathology to return to good subjective function, with modest deficits in calf strength compared with the uninjured side. Overall knee flexion strength did not appear impaired. These results suggest that hamstring autograft reconstruction is a viable method to treat these complex cases involving a lack of healthy tissue, allowing patients to return to symptom-free physical function and athletic activity. Level IV, case series.

A Proof of Principle Study Conducted by Community-Dwelling Seniors Using a Novel Passive Gait Assist System

It is vital for rehabilitating patients to perform as many task-related exercises as possible. These patients often need either force or trajectory assistance in order to perform gait. While this can be provided in the form of traditional gait rehabilitation or currently emerging robot-assisted gait training, there is a need for an affordable means to assist gait training. In this study, we present a passive gait assistance device that is composed of a spring-bar system attached to an elastic cord and a specialized shoe. The shoe has two straps attached such that both plantar and dorsiflexion torque can be applied to the user depending on the angle of the pulling force. The merit of the devices is that it is an affordable means to provide the user with gait assistance while allowing some freedom of one’s foot movement. We show that, with 20 community-dwelling seniors, our system successfully produces plantar flexion and dorsiflexion torque according to the gait cycle. Furthermore, electromyography analysis suggests that plantar flexor demand during the late stance phase and dorsiflexor demand during the swing phase are significantly reduced.

Alterations in neuromuscular junction morphology with ageing and endurance training modulate neuromuscular transmission and myofibre composition.

Both ageing and exercise training affect the neuromuscular junction (NMJ) structure. Morphological alterations in the NMJ have been considered to influence neuromuscular transmission and myofibre properties, but the direct link between the morphology and function has yet to be established. We measured the neuromuscular transmission, myofibre composition and NMJ structure of 5-month-old (young) and 24-month-old untrained (aged control) and trained (aged trained) mice. Aged trained mice were subjected to 2 months of endurance training before the measurement. Neuromuscular transmission was evaluated in vivo as the ratio of ankle plantar flexion torque evoked by the sciatic nerve stimulation to that by direct muscle stimulation. The torque ratio was significantly lower in aged mice than in young and aged trained mice at high-frequency stimulations, showing a significant positive correlation with voluntary grip strength. The degree of pre- to post-synaptic overlap of the NMJ was also significantly lower in aged mice and positively correlated with the torque ratio. We also found that the proportion of fast-twitch fibres in the soleus muscle decreased with age, and that age-related denervation occurred preferentially in fast-twitch fibres. Age-related denervation and a shift in myofibre composition were partially prevented by endurance training. These results suggest that age-related deterioration of the NMJ structure impairs neuromuscular transmission and alters myofibre composition, but these alterations can be prevented by structural amelioration of NMJ with endurance training. Our findings highlight the importance of the NMJ as a major determinant of age-related deterioration of skeletal muscles and the clinical significance of endurance training as a countermeasure. KEY POINTS: The neuromuscular junction (NMJ) plays an essential role in neuromuscular transmission and the maintenance of myofibre properties. We show that neuromuscular transmission is impaired with ageing but recovered by endurance training, which contributes to alterations in voluntary strength. Neuromuscular transmission is associated with the degree of pre- to post-synaptic overlap of the NMJ. Age-related denervation of fast-twitch fibres and a shift in myofibre composition toward a slower phenotype are partially prevented by endurance training. Our study provides substantial evidence that age-related and exercise-induced alterations in neuromuscular transmission and myofibre properties are associated with morphological changes in the NMJ.

Optimizing exoskeleton assistance to improve walking speed and energy economy for older adults

BackgroundWalking speed and energy economy tend to decline with age. Lower-limb exoskeletons have demonstrated potential to improve either measure, but primarily in studies conducted on healthy younger adults. Promising techniques like optimization of exoskeleton assistance have yet to be tested with older populations, while speed and energy consumption have yet to be simultaneously optimized for any population.MethodsWe investigated the effectiveness of human-in-the-loop optimization of ankle exoskeletons with older adults. Ten healthy adults > 65 years of age (5 females; mean age: 72 ± 3 yrs) participated in approximately 240 min of training and optimization with tethered ankle exoskeletons on a self-paced treadmill. Multi-objective human-in-the-loop optimization was used to identify assistive ankle plantarflexion torque patterns that simultaneously improved self-selected walking speed and metabolic rate. The effects of optimized exoskeleton assistance were evaluated in separate trials.ResultsOptimized exoskeleton assistance improved walking performance for older adults. Both objectives were simultaneously improved; self-selected walking speed increased by 8% (0.10 m/s; p = 0.001) and metabolic rate decreased by 19% (p = 0.007), resulting in a 25% decrease in energetic cost of transport (p = 8e-4) compared to walking with exoskeletons applying zero torque. Compared to younger participants in studies optimizing a single objective, our participants required lower exoskeleton torques, experienced smaller improvements in energy use, and required more time for motor adaptation.ConclusionsOur results confirm that exoskeleton assistance can improve walking performance for older adults and show that multiple objectives can be simultaneously addressed through human-in-the-loop optimization.

Does spastic myopathy determine active movement and ambulation speed in chronic spastic paresis?-A cross-sectional study on plantar flexors.

Functional correlates of spastic myopathy, the muscle disorder of spastic paresis, are unknown. To explore reciprocal relationships between clinical and structural parameters of plantar flexors with i) ambulation speed, ii) dorsiflexion and plantarflexion torques in chronic hemiparesis. Cross-sectional trial in chronic stroke-induced hemiparesis (>6 months). Plantar flexors were quantified through i) the Five Step Assessment: maximal extensibility (XV1), active range of dorsiflexion (XA); ii) ultrasonography: fascicle length (Lf) and thickness (Th) of medial gastrocnemius (GAS) and soleus (SOL), knee extended in an isokinetic ergometer, ankle at 80% XV1-GAS. Maximal isometric torques in plantar flexion (PF) and dorsiflexion (DF) and maximal barefoot 10-meter ambulation speed were collected. Relationships between structural, biomechanical, clinical and functional parameters were explored using non-parametric testing (Spearman). Twenty-one subjects (age 58.0±8.4, mean±SD, time since lesion 7.8±5.7 years) were recruited, with the following characteristics: ambulation speed, 0.77±0.37m/sec; XV1-SOL 92.7±10.3°; XV1-GAS 91.3±9.6°; XA-SOL 86.9±10.0°; XA-GAS 7676±14.2°; LfGAS, 58.2±18.3mm; ThGAS, 17.1±3.6 mm; LfSOL, 36.0±9.6 mm; ThSOL, 13.8±3.3mm; PF peak-torque 46.5±34.1Nm, DF peak-torque, 20.1±19.1Nm. XA-SOL and XA-GAS strongly correlated with XV1-SOL and XV1-GAS respectively (ρ = 0.74, p = 4E-04; resp ρ = 0.60, p = 0.0052). Ambulation speed moderately correlated with LfGAS (ρ = 0.51, p = 0.054), ThGAS (ρ = 0.58, p = 0.02) and LfSOL (ρ = 0.63, p = 0.009). DF and PF peak-torques both correlated with LfGAS (ρ = 0.53, p = 0.04) a; resp. ρ = 0.71, p = 0.0015). In chronic hemiparesis, active dorsiflexion is mostly determined by plantar flexor extensibility. Plantar flexor fascicle shortening is associated with reduced ambulation speed and ankle torques. Attempts to restore plantar flexor extensibility might be important objectives for gait rehabilitation in chronic hemiparesis.

BiLSTM-Based Joint Torque Prediction From Mechanomyogram During Isometric Contractions: A Proof of Concept Study.

Quantifying muscle strength is an important measure in clinical settings; however, there is a lack of practical tools that can be deployed for routine assessment. The purpose of this study is to propose a deep learning model for ankle plantar flexion torque prediction from time-series mechanomyogram (MMG) signals recorded during isometric contractions (i.e., a similar form to manual muscle testing procedure in clinical practice) and to evaluate its performance. Four different deep learning models in terms of model architecture (based on a stacked bidirectional long short-term memory and dense layers) were designed with different combinations of the number of units (from 32 to 512) and dropout ratio (from 0.0 to 0.8), and then evaluated for prediction performance by conducting the leave-one-subject-out cross-validation method from the 10-subject dataset. As a result, the models explained more variance in the untrained test dataset as the error metrics (e.g., root-mean-square error) decreased and as the slope of the relationship between the measured and predicted joint torques became closer to 1.0. Although the slope estimates appear to be sensitive to an individual dataset, >70% of the variance in nine out of 10 datasets was explained by the optimal model. These results demonstrated the feasibility of the proposed model as a potential tool to quantify average joint torque during a sustained isometric contraction.

OR29-04 Vitamin D Signaling Prevents Glucocorticoid-Induced Musculoskeletal Tissue Loss And Cardiac Dysfunction By Targeting The Atrogene Pathway

Abstract Disclosure: A. Sato: None. M. Cregor: None. B. Adhikari: None. M. Boerma: None. T. Bellido: None. Glucocorticoid excess increases the risk of bone fractures and induces cardiovascular events. Earlier studies demonstrated that glucocorticoids upregulate the expression of E3 ubiquitin ligases (atrogenes) in bone and skeletal/cardiac muscles, suggesting a common targetable pathway to prevent harmful glucocorticoid actions. Atrogenes stimulate proteasomal degradation of proteins, which promotes musculoskeletal tissue loss and cardiac dysfunction, known hallmarks of glucocorticoid disease. Here, we investigated whether Vitamin D receptor activation, which has beneficial musculoskeletal effects and may prevent falls, blocks glucocorticoid-induced activation of the atrogene pathway. Skeletally mature female 4-month-old C57Bl6 mice (N=12) were implanted with placebo or 2.1mg/kg/d prednisolone pellets for 8wks and received vehicle or 50ng/kg/d of 1,25D3 (calcitriol), 5x/wk, starting 3d before pellet implantation. In bone, 1,25D3 fully prevented decreases in spinal bone mineral density (BMD) and cancellous bone microarchitectural deterioration (low BV/TV and Tb.Th) induced by glucocorticoids. 1,25D3 prevented glucocorticoid-induced resorption, as quantified by circulating CTX and osteoclast number/surface. In contrast, 1,25D3 did not prevent glucocorticoid-induced suppression of bone formation, as quantified by circulating markers (P1NP and osteocalcin) and histomorphometric indexes (MS/BS and BFR). In skeletal muscle, 1,25D3 fully prevented glucocorticoid-induced loss of lean body mass, a muscle mass index measured by DEXA, and decreases in muscle strength, as determined by in vivo plantarflexion torque testing of the posterior hindlimb muscular compartment. Consistent with clinical evidence, cardiac echocardiography detected glucocorticoid dysfunction as exhibited by left ventricular (LV) wall thinning (anterior and posterior LVs at diastole and systole) and inefficient heart contraction (increased LV systolic volume, reduced ejection fraction and fractional shortening). Remarkably, 1,25D3 prevented the cardiac LV thinning and dysfunction induced by glucocorticoids. Neither glucocorticoid nor 1,25D3 altered heart mass, LV mass, or heart rate. 1,25D3 also prevented glucocorticoid increases in atrogene MuRF1 expression in cardiac and skeletal tissues. Additionally, 1,25D3 prevented glucocorticoid-induced increases in atrogene expression in separate ex vivo organ cultures of bone, skeletal muscle, and left ventricles of the heart, demonstrating direct Vitamin D actions. In conclusion, 1) atrogene upregulation is a central mechanistic hub underlying the damaging actions of glucocorticoid excess in bone, skeletal muscle, and the heart and 2) activation of Vitamin D receptor signaling preserves tissue structure and function by interfering with the atrogene pathway in musculoskeletal and cardiac systems. Presentation: Sunday, June 18, 2023

Single-Leg Hop Stabilization Throughout Concussion Recovery: A Preliminary Biomechanical Assessment.

Aberrant movement patterns among individuals with concussion history have been reported during sport-related movement. However, the acute postconcussion kinematic and kinetic biomechanical movement patterns during a rapid acceleration-deceleration task have not been profiled and leaves their progressive trajectory unknown. Our study aimed to examine single-leg hop stabilization kinematics and kinetics between concussed and healthy-matched controls acutely (≤7d) and when asymptomatic (≤72h of symptom resolution). Prospective, cohort laboratory study. Ten concussed (60% male; 19.2 [0.9]y; 178.7 [14.0]cm; 71.3 [18.0]kg) and 10 matched controls (60% male; 19.5 [1.2]y; 176.1 [12.6]cm; 71.0 [17.0]kg) completed the single-leg hop stabilization task under single and dual task (subtracting by 6's or 7's) at both time points. Participants stood on a 30-cm tall box set 50% of their height behind force plates while in an athletic stance. A synchronized light was illuminated randomly, queuing participants to initiate the movement as rapidly as possible. Participants then jumped forward, landed on their nondominant leg, and were instructed to reach and maintain stabilization as fast as possible upon ground contact. We used 2 (group) × 2 (time) mixed-model analyses of variance to compare single-leg hop stabilization outcomes separately during single and dual task. We observed a significant main group effect for single-task ankle plantarflexion moment, with greater normalized torque (mean difference = 0.03N·m/body weight; P = .048, g = 1.18) for concussed individuals across time points. A significant interaction effect for single-task reaction time indicated that concussed individuals had slower performance acutely relative to asymptomatic (mean difference = 0.09s; P = .015, g = 0.64), while control group performance was stable. No other main or interaction effects for single-leg hop stabilization task metrics were present during single and dual task (P ≥ .051). Greater ankle plantarflexion torque coupled with slower reaction time may indicate stiff, conservative single-leg hop stabilization performance acutely following concussion. Our findings shed preliminary light on the recovery trajectories of biomechanical alterations following concussion and provide specific kinematic and kinetic focal points for future research.

Acute intermittent hypoxia enhances strength, and modulates spatial distribution of muscle activation in persons with chronic incomplete spinal cord injury

Acute intermittent hypoxia (AIH) is an emerging technique for facilitating neural plasticity in individuals with chronic incomplete spinal cord injury (iSCI). A single sequence of AIH enhances hand grip strength and ankle plantarflexion torque, but underlying mechanisms are not yet clear. We sought to examine how AIH-induced changes in magnitude and spatial distribution of the electromyogram (EMG) of the biceps and triceps brachii contributes to improved strength. Seven individuals with iSCI visited the laboratory on two occasions, and received either AIH or Sham AIH intervention in a randomized order. AIH consisted of 15 brief (∼60s) periods of low oxygen (fraction of inspired O2 = 0.09) alternating with 60s of normoxia, whereas Sham AIH consisted of repeated exposures to normoxic air. High-density surface EMG of biceps and triceps brachii was recorded during maximal elbow flexion and extension. We then generated spatial maps which distinguished active muscle regions prior to and 60 min after AIH or Sham AIH. After an AIH sequence, elbow flexion and extension forces increased by 91.7 ± 88.4% and 51.7 ± 57.8% from baseline, respectively, whereas there was no difference after Sham AIH. Changes in strength were associated with an altered spatial distribution of EMG and increased root mean squared EMG amplitude in both biceps and triceps brachii muscles. These data suggest that altered motor unit activation profiles may underlie improved volitional strength after a single dose of AIH and warrant further investigation using single motor unit analysis techniques to further elucidate mechanisms of AIH-induced plasticity.

Exploration of muscle–tendon biomechanics one year after Achilles tendon rupture and the compensatory role of flexor hallucis longus

Achilles tendon (AT) rupture leads to long-term structural and functional impairments. Currently, the predictors of good recovery after rupture are poorly known. Thus, we aimed to explore the interconnections between structural, mechanical, and neuromuscular parameters and their associations with factors that could explain good recovery in patients with non-surgically treated AT rupture. A total of 35 patients with unilateral rupture (6 females) participated in this study. Muscle-tendon structural, mechanical, and neuromuscular parameters were measured 1-year after rupture. Interconnections between the inter-limb differences (Δ) were explored using partial correlations, followed by multivariable linear regression to find associations between the measured factors and the following markers that indicate good recovery: 1) tendon length, 2) tendon non-uniform displacement, and 3) flexor hallucis longus (FHL) normalized EMG amplitude difference between limbs. Δmedial gastrocnemius (MG) (β = −0.12, p = 0.007) and Δlateral gastrocnemius (β = −0.086, p = 0.030) subtendon lengths were associated with MG tendon Δstiffness. MG (β = 11.56, p = 0.003) and soleus (β = 2.18, p = 0.040) Δsubtendon lengths explained 48 % of variance in FHL EMG amplitude. Regression models for tendon length and non-uniform displacement were not significant. Smaller inter-limb differences in Achilles subtendon lengths were associated with smaller differences in the AT stiffness between limbs, and a smaller contribution of FHL muscle to the plantarflexion torque. In the injured limb, the increased contribution of FHL appears to partially counteract a smaller contribution from MG due to the elongated tendon, however the role of FHL should not be emphasized during rehabilitation to allow recovery of the TS muscles.

Abstract 365: Targeting FGF21 inhibits tumor growth and attenuates cachexia in experimental colorectal cancer

Abstract Background: Colorectal cancer (CRC) is frequently accompanied by cachexia, an uncured multi-organ wasting syndrome, debilitating musculoskeletal health, physical function, and overall survival. Fibroblast growth factor 21 (FGF21) is a modulator of musculoskeletal health and metabolism and has been associated with CRC risk and progression. Here, we investigated the effects of tumor derived FGF21 on musculoskeletal health in CRC. Methods: Plasma from CRC patients and preclinical models of CRC (C26, MC38) were assessed for circulating FGF21 levels, and CRC cell lines (C26, MC38, HCT116) were screened for FGF21 expression. Using CRISPR/Cas9 technology, FGF21 was deleted from MC38 cells (KO-MC38). 8-week-old male C57BL/6J mice were subcutaneously injected (1.0x106) with wild-type (WT-MC38) or FGF21-/- (KO-MC38) MC38 tumor cells, while experimental control animals received saline (n = 10-13/group). Animals underwent electrophysiological testing to obtain motor unit number estimation (MUNE) 48 hours prior to euthanasia and were assessed for maximum plantarflexion torque 24 hours prior to euthanasia. At the time of euthanasia, plasma was collected for assessment of systemic FGF21, while tumors and skeletal muscles (gastrocnemius, quadriceps, and tibialis anterior) were excised and weighed. Femur bones were processed for microcomputed tomography (µCT) imaging and analysis. Results: CRC patients and MC38 tumor hosts demonstrated elevated circulating plasma FGF21 (p&amp;lt;0.05) compared to controls. Gene expression of CRC cells revealed an 11-fold increase of FGF21 in MC38 compared to C26 and HCT116 cells. WT-MC38 tumor hosts had elevated plasma FGF21 (4-fold; p&amp;lt;0.05) compared to control, which was unchanged in KO-MC38 hosts. In line with the development of cachexia, WT-MC38 hosts displayed reductions in muscle mass (gastrocnemius: -5%; p&amp;lt;0.05, quadriceps: -10%; p&amp;lt;0.01, tibialis anterior: -8%; p&amp;lt;0.01), MUNE (-31%; p&amp;lt;0.01), and plantarflexion torque (-10%; p&amp;lt;0.05). Meanwhile, µCT of femur bones demonstrated reductions in trabecular bone volume fraction (BV/TV: -30%; p&amp;lt;0.05) and cortical cross-sectional thickness (Cs.Th: -14%; p&amp;lt;0.05) in WT-MC38 hosts compared to experimental controls. Conversely, when compared to WT-MC38, KO-MC38 hosts had preserved skeletal muscle mass (gastrocnemius: +7%; p&amp;lt;0.01, quadriceps: +13%; p&amp;lt;0.001, tibialis anterior: +8%; p&amp;lt;0.001), MUNE (+47%; p&amp;lt;0.01), plantarflexion torque (+8%; p&amp;lt;0.05), and bone mass (BV/TV: +69%; p&amp;lt;0.001, Cs.Th: +23%; p&amp;lt;0.001). Strikingly, the mass of KO-MC38 tumors was reduced 75% (p&amp;lt;0.01) compared to WT-MC38 tumors. Conclusion: Our data suggest that targeting CRC-derived FGF21 halts tumor growth, resulting in preservation of musculoskeletal health and function. Thus, counteracting tumor-derived FGF21 may serve as a therapeutic intervention against the progression of cancer and cancer-associated cachexia. Citation Format: Fabrizio Pin, Anika Shimonty, Joshua Robert Huot. Targeting FGF21 inhibits tumor growth and attenuates cachexia in experimental colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 365.

Mechanical disturbances applied by motorized ankle foot orthosis to adapt ankle muscles activation-A validation study.

Background: Reduced function of ankle muscles usually leads to impaired gait. Motorized ankle foot orthoses (MAFOs) have shown potential to improve neuromuscular control and increase volitional engagement of ankle muscles. In this study, we hypothesize that specific disturbances (adaptive resistance-based perturbations to the planned trajectory) applied by a MAFO can be used to adapt the activity of ankle muscles. The first goal of this exploratory study was to test and validate two different ankle disturbances based on plantarflexion and dorsiflexion resistance while training in standing still position. The second goal was to assess neuromuscular adaptation to these approaches, namely, in terms of individual muscle activation and co-activation of antagonists. Methods: Two ankle disturbances were tested in ten healthy subjects. For each subject, the dominant ankle followed a target trajectory while the contralateral leg was standing still: a) dorsiflexion torque during the first part of the trajectory (Stance Correlate disturbance-StC), and b) plantarflexion torque during the second part of the trajectory (Swing Correlate disturbance-SwC). Electromyography was recorded from the tibialis anterior (TAnt) and gastrocnemius medialis (GMed) during MAFO and treadmill (baseline) trials. Results: GMed (plantarflexor muscle) activation decreased in all subjects during the application of StC, indicating that dorsiflexion torque did not enhance GMed activity. On the other hand, TAnt (dorsiflexor muscle) activation increased when SwC was applied, indicating that plantarflexion torque succeeded in enhancing TAnt activation. For each disturbance paradigm, there was no antagonist muscle co-activation accompanying agonist muscle activity changes. Conclusion: We successfully tested novel ankle disturbance approaches that can be explored as potential resistance strategies in MAFO training. Results from SwC training warrant further investigation to promote specific motor recovery and learning of dorsiflexion in neural-impaired patients. This training can potentially be beneficial during intermediate phases of rehabilitation prior to overground exoskeleton-assisted walking. Decreased activation of GMed during StC might be attributed to the unloaded body weight in the ipsilateral side, which typically decreases activation of anti-gravity muscles. Neural adaptation to StC needs to be studied thoroughly in different postures in futures studies.