Making sense of proprioception.

Proprioception - the sense of body position in space - is intimately linked to motor control. Here, we briefly review the current knowledge of the proprioceptive system and how advances in the genetic characterisation of proprioceptive sensory neurons in mice promise to dissect its role in health and disease.

Spatiotemporal modulation of a common set of muscle synergies during unpredictable and predictable gait perturbations in older adults.

Muscle synergies as functional low-dimensional building blocks of the neuromotor system regulate the activation patterns of muscle groups in a modular structure during locomotion. The purpose of the current study was to explore how older adults organize locomotor muscle synergies to counteract unpredictable and predictable gait perturbations during the perturbed steps and the recovery steps. Sixty-three healthy older adults (71.2±5.2 years) participated in the study. Mediolateral and anteroposterior unpredictable and predictable perturbations during walking were introduced using a treadmill. Muscle synergies were extracted from the electromyographic activity of 13 lower limb muscles using Gaussian non-negative matrix factorization. The four basic synergies responsible for unperturbed walking (weight acceptance, propulsion, early swing and late swing) were preserved in all applied gait perturbations, yet their temporal recruitment and muscle contribution in each synergy were modified (P<0.05). These modifications were observed for up to four recovery steps and were more pronounced (P<0.05) following unpredictable perturbations. The recruitment of the four basic walking synergies in the perturbed and recovery gait cycles indicates a robust neuromotor control of locomotion by using activation patterns of a few and well-known muscle synergies with specific adjustments within the synergies. The selection of pre-existing muscle synergies while adjusting the time of their recruitment during challenging locomotor conditions may improve the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations.

Muscle spindles and their role in maintaining robust locomotion.

Muscle spindles, one of the two main classes of proprioceptors together with Golgi tendon organs, are sensory structures that keep the central nervous system updated about the position and movement of body parts. Although they were discovered more than 150 years ago, their function during movement is not yet fully understood. Here, we summarize the morphology and known functions of muscle spindles, with a particular focus on locomotion. Although certain properties such as the sensitivity to dynamic and static muscle stretch are long known, recent advances in molecular biology have allowed the characterization of the molecular mechanisms for signal transduction in muscle spindles. Building upon classic literature showing that a lack of sensory feedback is deleterious to locomotion, we bring to the discussion more recent findings that support a pivotal role of muscle spindles in maintaining murine and human locomotor robustness, defined as the ability to cope with perturbations. Yet, more research is needed to expand the existing mechanistic understanding of how muscle spindles contribute to the production of robust, functional locomotion in real world settings. Future investigations should focus on combining different animal models to identify, in health and disease, those peripheral, spinal and brain proprioceptive structures involved in the fine tuning of motor control when locomotion happens in challenging conditions.

The brain integrates proprioceptive information to ensure robust locomotion.

Robust locomotion relies on information from proprioceptors: sensory organs that communicate the position of body parts to the spinal cord and brain. Proprioceptive circuits in the spinal cord are known to coarsely regulate locomotion in the presence of perturbations. Yet, the regulatory importance of the brain in maintaining robust locomotion remains less clear. Here, through mouse genetic studies and in vivo electrophysiology, we examined the role of the brain in integrating proprioceptive information during perturbed locomotion. The systemic removal of proprioceptors left the mice in a constantly perturbed state, similar to that observed during mechanically perturbed locomotion in wild-type mice and characterised by longer and less accurate synergistic activation patterns. By contrast, after surgically interrupting the ascending proprioceptive projection to the brain through the dorsal column of the spinal cord, wild-type mice showed normal walking behaviour, yet lost the ability to respond to external perturbations. Our findings provide direct evidence of a pivotal role for ascending proprioceptive information in achieving robust, safe locomotion. KEY POINTS: Whether brain integration of proprioceptive feedback is crucial for coping with perturbed locomotion is not clear. We showed a crucial role of the brain for responding to external perturbations and ensure robust locomotion. We used mouse genetics to remove proprioceptors and a spinal lesion model to interrupt the flow of proprioceptive information to the brain through the dorsal column in wild-type animals. Using a custom-built treadmill, we administered sudden and random mechanical perturbations to mice during walking. External perturbations affected locomotion in wild-type mice similar to the absence of proprioceptors in genetically modified mice. Proprioceptive feedback from muscle spindles and Golgi tendon organs contributed to locomotor robustness. Wild-type mice lost the ability to respond to external perturbations after interruption of the ascending proprioceptive projection to the brainstem.

Measuring Kinematic Response to Perturbed Locomotion in Young Adults.

Daily life activities often require humans to perform locomotion in challenging scenarios. In this context, this study aimed at investigating the effects induced by anterior-posterior (AP) and medio-lateral (ML) perturbations on walking. Through this aim, the experimental protocol involved 12 participants who performed three tasks on a treadmill consisting of one unperturbed and two perturbed walking tests. Inertial measurement units were used to gather lower limb kinematics. Parameters related to joint angles, as the range of motion (ROM) and its variability (CoV), as well as the inter-joint coordination in terms of continuous relative phase (CRP) were computed. The AP perturbation seemed to be more challenging causing differences with respect to normal walking in both the variability of the ROM and the CRP amplitude and variability. As ML, only the ankle showed different behavior in terms of joint angle and CRP variability. In both tasks, a shortening of the stance was found. The findings should be considered when implementing perturbed rehabilitative protocols for falling reduction.

Enthalpy efficiency of the soleus muscle contributes to improvements in running economy.

During human running, the soleus, as the main plantar flexor muscle, generates the majority of the mechanical work through active shortening. The fraction of chemical energy that is converted into muscular work (enthalpy efficiency) depends on the muscle shortening velocity. Here, we investigated the soleus muscle fascicle behaviour during running with respect to the enthalpy efficiency as a mechanism that could contribute to improvements in running economy after exercise-induced increases of plantar flexor strength and Achilles tendon (AT) stiffness. Using a controlled longitudinal study design (n = 23) featuring a specific 14-week muscle-tendon training, increases in muscle strength (10%) and tendon stiffness (31%) and reduced metabolic cost of running (4%) were found only in the intervention group (n = 13, p < 0.05). Following training, the soleus fascicles operated at higher enthalpy efficiency during the phase of muscle-tendon unit (MTU) lengthening (15%) and in average over stance (7%, p < 0.05). Thus, improvements in energetic cost following increases in plantar flexor strength and AT stiffness seem attributed to increased enthalpy efficiency of the operating soleus muscle. The results further imply that the soleus energy production in the first part of stance, when the MTU is lengthening, may be crucial for the overall metabolic energy cost of running.

Fractal analysis of muscle activity patterns during locomotion: pitfalls and how to avoid them.

Time-dependent physiological data sets are often difficult to interpret objectively. Biosignals such as electromyogram, electroencephalogram, or single-neuron recordings can be interpreted using various linear and nonlinear methods. Each analysis technique aims at the explanation of different data features that might be visible or not to the naked eye. Here, we used linear decomposition based on machine learning to extract motor primitives (the time-dependent coefficients of muscle synergies) from the hindlimb electromyographic activity of mice during normal and mechanically perturbed locomotion. We set out to investigate the effects of calculation parameters and data quality on two nonlinear metrics derived from fractal analysis: the Higuchi's fractal dimension (HFD) and the Hurst exponent (H). Both HFD and H proved to be exceptionally sensitive to changes in motor primitives induced by external perturbations to locomotion. We discuss the potential pitfalls that might arise from fractal analysis by using examples based on surrogate data. We conclude giving some simple, data-driven suggestions to reduce the chance of misinterpretations when metrics such as HFD and H are applied to any biological signal containing elements of periodicity.NEW & NOTEWORTHY Despite the lack of consensus on how to perform fractal analysis of physiological time series, many studies rely on this technique. Here, we shed light on the potential pitfalls of using the Higuchi's fractal dimension and the Hurst exponent. We expose and suggest how to solve the drawbacks of such methods when applied to data from normal and perturbed locomotion by combining in vivo recordings and computational approaches.

Muscle Synergies in Parkinson's Disease.

Over the last two decades, experimental studies in humans and other vertebrates have increasingly used muscle synergy analysis as a computational tool to examine the physiological basis of motor control. The theoretical background of muscle synergies is based on the potential ability of the motor system to coordinate muscles groups as a single unit, thus reducing high-dimensional data to low-dimensional elements. Muscle synergy analysis may represent a new framework to examine the pathophysiological basis of specific motor symptoms in Parkinson's disease (PD), including balance and gait disorders that are often unresponsive to treatment. The precise mechanisms contributing to these motor symptoms in PD remain largely unknown. A better understanding of the pathophysiology of balance and gait disorders in PD is necessary to develop new therapeutic strategies. This narrative review discusses muscle synergies in the evaluation of motor symptoms in PD. We first discuss the theoretical background and computational methods for muscle synergy extraction from physiological data. We then critically examine studies assessing muscle synergies in PD during different motor tasks including balance, gait and upper limb movements. Finally, we speculate about the prospects and challenges of muscle synergy analysis in order to promote future research protocols in PD.

Modular organization of murine locomotor pattern in the presence and absence of sensory feedback from muscle spindles.

KEY POINTS: Locomotion on land and in water requires the coordination of a great number of muscle activations and joint movements. Constant feedback about the position of own body parts in relation to the surrounding environment and the body itself (proprioception) is required to maintain stability and avoid failure. The central nervous system may follow a modular type of organization by controlling muscles in orchestrated groups (muscle synergies) rather than individually. We used this concept on genetically modified mice lacking muscle spindles, one of the two main classes of proprioceptors. We provide evidence that proprioceptive feedback is required by the central nervous system to accurately tune the modular organization of locomotion. ABSTRACT: For exploiting terrestrial and aquatic locomotion, vertebrates must build their locomotor patterns based on an enormous amount of variables. The great number of muscles and joints, together with the constant need for sensory feedback information (e.g. proprioception), make the task of controlling movement a problem with overabundant degrees of freedom. It is widely accepted that the central nervous system may simplify the creation and control of movement by generating activation patterns common to muscle groups, rather than specific to individual muscles. These activation patterns, called muscle synergies, describe the modular organization of movement. We extracted synergies through electromyography from the hind limb muscle activities of wild-type and genetically modified mice lacking sensory feedback from muscle spindles. Muscle spindle-deficient mice underwent a modification of the temporal structure (motor primitives) of muscle synergies that resulted in diminished functionality during walking. In addition, both the temporal and spatial (motor modules) components of synergies were severely affected when external perturbations were introduced or when animals were immersed in water. These findings show that sensory feedback from group Ia/II muscle spindles regulates motor function in normal and perturbed walking. Moreover, when group Ib Golgi tendon organ feedback is lacking due to enhanced buoyancy, the modular organization of swimming is almost completely compromised.

The force-length-velocity potential of the human soleus muscle is related to the energetic cost of running.

According to the force-length-velocity relationships, the muscle force potential is determined by the operating length and velocity, which affects the energetic cost of contraction. During running, the human soleus muscle produces mechanical work through active shortening and provides the majority of propulsion. The trade-off between work production and alterations of the force-length and force-velocity potentials (i.e. fraction of maximum force according to the force-length-velocity curves) might mediate the energetic cost of running. By mapping the operating length and velocity of the soleus fascicles onto the experimentally assessed force-length and force-velocity curves, we investigated the association between the energetic cost and the force-length-velocity potentials during running. The fascicles operated close to optimal length (0.90 ± 0.10 L0) with moderate velocity (0.118 ± 0.039 Vmax [maximum shortening velocity]) and, thus, with a force-length potential of 0.92 ± 0.07 and a force-velocity potential of 0.63 ± 0.09. The overall force-length-velocity potential was inversely related (r = -0.52, p = 0.02) to the energetic cost, mainly determined by a reduced shortening velocity. Lower shortening velocity was largely explained (p < 0.001, R2 = 0.928) by greater tendon gearing, shorter Achilles tendon lever arm, greater muscle belly gearing and smaller ankle angle velocity. Here, we provide the first experimental evidence that lower shortening velocities of the soleus muscle improve running economy.

Short- and long-term effects of altered point of ground reaction force application on human running energetics.

The current study investigates the effect of altering the point of force application (PFA) from the rearfoot towards the fore of the foot on the metabolic energy consumption and the influence of transitioning to this technique over a short or a longer timeframe. The participants were randomly assigned into two experimental and one control group: a short-term intervention group (STI, N=17; two training sessions), a long-term intervention group (LTI, N=10; 14-week gradual transition) and a control group (CG, N=11). Data were collected at two running velocities (2.5 and 3.0 m s-1). The cost coefficient (i.e. energy required per unit of vertical ground reaction force; J N-1) decreased (P<0.001) after both interventions due to a more anterior PFA during running (STI: 12%, LTI: 11%), but led to a higher (P<0.001) rate of force generation (STI: 17%, LTI: 15.2%). Dynamic stability of running showed a significant (P<0.001) decrease in the STI (2.1%), but no differences (P=0.673) in the LTI. The rate of metabolic energy consumption increased in the STI (P=0.038), but remained unchanged in the LTI (P=0.660). The CG had no changes. These results demonstrate that the cost coefficient was successfully decreased following an alteration in the running technique towards a more anterior PFA. However, the energy consumption remained unchanged because of a simultaneous increase in rate of force generation due to a decreased contact time per step. The increased instability found during the short-term intervention and its neutralization after the long-term intervention indicates a role of motor control errors in the economy of running after acute alterations in habitual running execution.

Modular control during incline and level walking in humans.

The neuromuscular control of human movement can be described by a set of muscle synergies factorized from myoelectric signals. There is some evidence that the selection, activation and flexible combination of these basic activation patterns are of a neural origin. We investigated the muscle synergies during incline and level walking to evaluate changes in the modular organization of neuromuscular control related to changes in the mechanical demands. Our results revealed five fundamental (not further factorizable) synergies for both walking conditions but with different frequencies of appearance of the respective synergies during incline compared with level walking. Low similarities across conditions were observed in the timing of the activation patterns (motor primitives) and the weightings of the muscles within the respective elements (motor modules) for the synergies associated with the touchdown, mid-stance and early push-off phase. The changes in neuromuscular control could be attributed to changes in the mechanical demands in support, propulsion and medio-lateral stabilization of the body during incline compared with level walking. Our findings provide further evidence that the central nervous system flexibly uses a consistent set of neural control elements with a flexible temporal recruitment and modifications of the relative muscle weightings within each element to provide stable locomotion under varying mechanical demands during walking.

"Biofeedback-based return to sport": individualization through objective assessments.

Elite athletes are regularly exposed to high and repetitive mechanical stresses and impacts, resulting in high injury rates. The consequences of injury can range from time lost from training and competition to chronic physical and psychological burden, with no guarantee that the athlete will return to preinjury levels of sport activity and performance. Prominent predictors include load management and previous injury, highlighting the importance of the postinjury period for effective return to sport (RTS). Currently, there is conflicting information on how to choose and assess the best reentry strategy. Treating RTS as a continuum, with controlled progression of training load and complexity, seems to provide benefits in this process. Furthermore, objectivity has been identified as a critical factor in improving the effectiveness of RTS. We propose that assessments derived from biomechanical measurements in functional settings can provide the objectivity needed for regular biofeedback cycles. These cycles should aim to identify weaknesses, customize the load, and inform on the status of RTS progress. This approach emphasizes individualization as the primary determinant of RTS and provides a solid foundation for achieving it.

Comparable in vivo joint kinematics between self-reported stable and unstable knees after TKA can be explained by muscular adaptation strategies: A retrospective observational study.

Background: Postoperative knee instability is one of the major reasons accounting for unsatisfactory outcomes, as well as a major failure mechanism leading to total knee arthroplasty (TKA) revision. Nevertheless, subjective knee instability is not well defined clinically, plausibly because the relationships between instability and implant kinematics during functional activities of daily living remain unclear. Although muscles play a critical role in supporting the dynamic stability of the knee joint, the influence of joint instability on muscle synergy patterns is poorly understood. Therefore, this study aimed to understand the impact of self-reported joint instability on tibiofemoral kinematics and muscle synergy patterns after TKA during functional gait activities of daily living. Methods: Tibiofemoral kinematics and muscle synergy patterns were examined during level walking, downhill walking, and stair descent in eight self-reported unstable knees after TKA (3M:5F, 68.9 ± 8.3 years, body mass index [BMI] 26.1 ± 3.2 kg/m2, 31.9 ± 20.4 months postoperatively), and compared against 10 stable TKA knees (7M:3F, 62.6 ± 6.8 years, 33.9 ± 8.5 months postoperatively, BMI 29.4 ± 4.8 kg/m2). For each knee joint, clinical assessments of postoperative outcome were performed, while joint kinematics were evaluated using moving video-fluoroscopy, and muscle synergy patterns were recorded using electromyography. Results: Our results reveal that average condylar A-P translations, rotations, as well as their ranges of motion were comparable between stable and unstable groups. However, the unstable group exhibited more heterogeneous muscle synergy patterns and prolonged activation of knee flexors compared to the stable group. In addition, subjects who reported instability events during measurement showed distinct, subject-specific tibiofemoral kinematic patterns in the early/mid-swing phase of gait. Conclusions: Our findings suggest that accurate movement analysis is sensitive for detecting acute instability events, but might be less robust in identifying general joint instability. Conversely, muscle synergy patterns seem to be able to identify muscular adaptation associated with underlying chronic knee instability. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Sex-specific tuning of modular muscle activation patterns for locomotion in young and older adults.

There is increasing evidence that including sex as a biological variable is of crucial importance to promote rigorous, repeatable and reproducible science. In spite of this, the body of literature that accounts for the sex of participants in human locomotion studies is small and often produces controversial results. Here, we investigated the modular organization of muscle activation patterns for human locomotion using the concept of muscle synergies with a double purpose: i) uncover possible sex-specific characteristics of motor control and ii) assess whether these are maintained in older age. We recorded electromyographic activities from 13 ipsilateral muscles of the lower limb in young and older adults of both sexes walking (young and old) and running (young) on a treadmill. The data set obtained from the 215 participants was elaborated through non-negative matrix factorization to extract the time-independent (i.e., motor modules) and time-dependent (i.e., motor primitives) coefficients of muscle synergies. We found sparse sex-specific modulations of motor control. Motor modules showed a different contribution of hip extensors, knee extensors and foot dorsiflexors in various synergies. Motor primitives were wider (i.e., lasted longer) in males in the propulsion synergy for walking (but only in young and not in older adults) and in the weight acceptance synergy for running. Moreover, the complexity of motor primitives was similar in younger adults of both sexes, but lower in older females as compared to older males. In essence, our results revealed the existence of small but defined sex-specific differences in the way humans control locomotion and that these are not entirely maintained in older age.

Sex influence on muscle synergies in a ballistic force-velocity test during the delayed recovery phase after a graded endurance run.

The acute and delayed phases of the functional recovery pattern after running exercise have been studied mainly in men. However, it seems that women are less fatigable and/or recover faster than men, at least when tested in isometric condition. After a 20 km graded running race, the influence of sex on the delayed phase of recovery at 2-4 days was studied using a horizontal ballistic force-velocity test. Nine female and height male recreational runners performed maximal concentric push-offs at four load levels a week before the race (PRE), 2 and 4 days (D2 and D4) later. Ground reaction forces and surface electromyographic (EMG) activity from 8 major lower limb muscles were recorded. For each session, the mechanical force-velocity-power profile (i.e. theoretical maximal values of force ( F ¯ 0), velocity ( V ¯ 0), and power ( P ¯ max)) was computed. Mean EMG activity of each recorded muscle and muscle synergies (three for both men and women) were extracted. Independently of the testing sessions, men and women differed regarding the solicitation of the bi-articular thigh muscles (medial hamstring muscles and rectus femoris). At mid-push-off, female made use of more evenly distributed lower limb muscle activities than men. No fatigue effect was found for both sexes when looking at the mean ground reaction forces. However, the force-velocity profile varied by sex throughout the recovery: only men showed a decrease of both V ¯ 0 (p < 0.05) and P ¯ max (p < 0.01) at D2 compared to PRE. Vastus medialis activity was reduced for both men and women up to D4, but only male synergies were impacted at D2: the center of activity of the first and second synergies was reached later. This study suggests that women could recover earlier in a dynamic multi-joint task and that sex-specific organization of muscle synergies may have contributed to their different recovery times after such a race.

Differences in muscle synergies among recovery responses limit inter-task generalisation of stability performance.

Generalisation of adaptations is key to effective stability control facing variety of postural threats during daily life activity. However, in a previous study we could demonstrate that adaptations to stability control do not necessarily transfer to an untrained motor task. Here, we examined the dynamic stability and modular organisation of motor responses to different perturbations (i.e. unpredictable gait-trip perturbations and subsequent loss of anterior stability in a lean-and-release protocol) in a group of young and middle-aged adults (n = 57; age range 19-53 years) to detect potential neuromotor factors limiting transfer of adaptations within the stability control system. We hypothesized that the motor system uses different modular organisation in recovery responses to tripping and lean-and-release, which may explain lack in positive transfer of adaptations in stability control. After eight trip-perturbations participants increased their dynamic stability during the first recovery step (p < 0.001), yet they showed no significant improvement to the untrained lean-and-release transfer task compared to controls who did not undergo the perturbation exposure (p = 0.44). Regarding the neuromuscular control of responses, lower number of synergies (3 vs. 4) was found for the lean-and-release compared to the gait-trip perturbation task, revealing profound differences in both the timing and function of the recruited muscles to match the biomechanical specificity of different perturbations. Our results provide indirect evidence that the motor system uses different modular organisation in diverse perturbation responses, what possibly inhibits inter-task generalisation of adaptations in stability control.

Runners Employ Different Strategies to Cope With Increased Speeds Based on Their Initial Strike Patterns.

In this paper we examined how runners with different initial foot strike pattern (FSP) develop their pattern over increasing speeds. The foot strike index (FSI) of 47 runners [66% initially rearfoot strikers (RFS)] was measured in six speeds (2.5-5.0 ms-1), with the hypotheses that the FSI would increase (i.e., move toward the fore of the foot) in RFS strikers, but remain similar in mid- or forefoot strikers (MFS) runners. The majority of runners (77%) maintained their original FSP by increasing speed. However, we detected a significant (16.8%) decrease in the FSI in the MFS group as a function of running speed, showing changes in the running strategy, despite the absence of a shift from one FSP to another. Further, while both groups showed a decrease in contact times, we found a group by speed interaction (p < 0.001) and specifically that this decrease was lower in the MFS group with increasing running speeds. This could have implications in the metabolic energy consumption for MFS-runners, typically measured at low speeds for the assessment of running economy.

Proactive Modulation in the Spatiotemporal Structure of Muscle Synergies Minimizes Reactive Responses in Perturbed Landings.

Stability training in the presence of perturbations is an effective means of increasing muscle strength, improving reactive balance performance, and reducing fall risk. We investigated the effects of perturbations induced by an unstable surface during single-leg landings on the mechanical loading and modular organization of the leg muscles. We hypothesized a modulation of neuromotor control when landing on the unstable surface, resulting in an increase of leg muscle loading. Fourteen healthy adults performed 50 single-leg landings from a 30 cm height onto two ground configurations: stable solid ground (SG) and unstable foam pads (UG). Ground reaction force, joint kinematics, and electromyographic activity of 13 muscles of the landing leg were measured. Resultant joint moments were calculated using inverse dynamics and muscle synergies with their time-dependent (motor primitives) and time-independent (motor modules) components were extracted via non-negative matrix factorization. Three synergies related to the touchdown, weight acceptance, and stabilization phase of landing were found for both SG and UG. When compared with SG, the motor primitive of the touchdown synergy was wider in UG (p < 0.001). Furthermore, in UG the contribution of gluteus medius increased (p = 0.015) and of gastrocnemius lateralis decreased (p < 0.001) in the touchdown synergy. Weight acceptance and stabilization did not show any statistically significant differences between the two landing conditions. The maximum ankle and hip joint moment as well as the rate of ankle, knee, and hip joint moment development were significantly lower (p < 0.05) in the UG condition. The spatiotemporal modifications of the touchdown synergy in the UG condition highlight proactive adjustments in the neuromotor control of landings, which preserve reactive adjustments during the weight acceptance and stabilization synergies. Furthermore, the performed proactive control in combination with the viscoelastic properties of the soft surface resulted in a reduction of the mechanical loading in the lower leg muscles. We conclude that the use of unstable surfaces does not necessarily challenge reactive motor control nor increase muscle loading per se. Thus, the characteristics of the unstable surface and the dynamics of the target task must be considered when designing perturbation-based interventions.

Muscle-specific economy of force generation and efficiency of work production during human running.

Human running features a spring-like interaction of body and ground, enabled by elastic tendons that store mechanical energy and facilitate muscle operating conditions to minimize the metabolic cost. By experimentally assessing the operating conditions of two important muscles for running, the soleus and vastus lateralis, we investigated physiological mechanisms of muscle work production and muscle force generation. We found that the soleus continuously shortened throughout the stance phase, operating as work generator under conditions that are considered optimal for work production: high force-length potential and high enthalpy efficiency. The vastus lateralis promoted tendon energy storage and contracted nearly isometrically close to optimal length, resulting in a high force-length-velocity potential beneficial for economical force generation. The favorable operating conditions of both muscles were a result of an effective length and velocity-decoupling of fascicles and muscle-tendon unit, mostly due to tendon compliance and, in the soleus, marginally by fascicle rotation.