Short-latency stretch reflexes depend on the balance of activity in agonist and antagonist muscles during ballistic elbow movements.

The spinal stretch reflex is a fundamental building block of motor function, with a sensitivity that varies continuously during movement and when changing between movement and posture. Many have investigated task-dependent reflex sensitivity, but few have provided simple, quantitative analyses of the relationship between the volitional control and stretch reflex sensitivity throughout tasks that require coordinated activity of several muscles. Here, we develop such an analysis and use it to test the hypothesis that modulation of reflex sensitivity during movement can be explained by the balance of activity within agonist and antagonist muscles better than by activity only in the muscle homonymous with the reflex. Subjects completed hundreds of flexion and extension movements as small, pseudorandom perturbations of elbow angle were applied to obtain estimates of stretch reflex amplitude throughout the movement. A subset of subjects performed a postural control task with muscle activities matched to those during movement. We found that reflex modulation during movement can be described by background activity in antagonist muscles about the elbow much better than by activity only in the muscle homonymous to the reflex (P < 0.001). Agonist muscle activity enhanced reflex sensitivity, whereas antagonist activity suppressed it. Surprisingly, the magnitude of these effects was similar, suggesting a balance of control between agonists and antagonists very different from the dominance of sensitivity to homonymous activity during posture. This balance is due to a large decrease in sensitivity to homonymous muscle activity during movement rather than substantial changes in the influence of antagonistic muscle activity.NEW & NOTEWORTHY This study examined the sensitivity of the stretch reflexes elicited in elbow muscles to the background activity in these same muscles during movement and postural tasks. We found a heightened reciprocal control of reflex sensitivity during movement that was not present during maintenance of posture. These results help explain previous discrepancies in reflex sensitivity measured during movement and posture and provide a simple model for assessing their contributions to muscle activity in both tasks.

Cancer survivors post-chemotherapy exhibit unimpaired short-latency stretch reflexes in the proximal upper extremity.

Oxaliplatin (OX) chemotherapy can lead to long-term sensorimotor impairments in cancer survivors. The impairments are often thought to be caused by OX-induced progressive degeneration of sensory afferents known as length-dependent dying-back sensory neuropathy. However, recent preclinical work has identified functional defects in the encoding of muscle proprioceptors and in motoneuron firing. These functional defects in the proprioceptive sensorimotor circuitry could readily impair muscle stretch reflexes, a fundamental building block of motor coordination. Given that muscle proprioceptors are distributed throughout skeletal muscle, defects in stretch reflexes could be widespread, including in the proximal region where dying-back sensory neuropathy is less prominent. All previous investigations on chemotherapy-related reflex changes focused on distal joints, leading to results that could be influenced by dying-back sensory neuropathy rather than more specific changes to sensorimotor circuitry. Our study extends this earlier work by quantifying stretch reflexes in the shoulder muscles in 16 cancer survivors and 16 healthy controls. Conduction studies of the sensory nerves in hand were completed to detect distal sensory neuropathy. We found no significant differences in the short-latency stretch reflexes (amplitude and latency) of the shoulder muscles between cancer survivors and healthy controls, contrasting with the expected differences based on the preclinical work. Our results may be linked to differences between the human and preclinical testing paradigms including, among many possibilities, differences in the tested limb or species. Determining the source of these differences will be important for developing a complete picture of how OX chemotherapy contributes to long-term sensorimotor impairments.NEW & NOTEWORTHY Our results showed that cancer survivors after oxaliplatin (OX) treatment exhibited stretch reflexes that were comparable with age-matched healthy individuals in the proximal upper limb. The lack of OX effect might be linked to differences between the clinical and preclinical testing paradigms. These findings refine our expectations derived from the preclinical study and guide future assessments of OX effects that may have been insensitive to our measurement techniques.

Non-linear properties of the Achilles tendon determine ankle impedance over a broad range of activations in humans.

Regulating ankle mechanics is essential for controlled interactions with the environment and rejecting unexpected disturbances. Ankle mechanics can be quantified by impedance, the dynamic relationship between an imposed displacement and the torque generated in response. Ankle impedance in the sagittal plane depends strongly on the triceps surae and Achilles tendon, but their relative contributions remain unknown. It is commonly assumed that ankle impedance is controlled by changing muscle activation and, thereby, muscle impedance, but this ignores that tendon impedance also changes with activation-induced loading. Thus, we sought to determine the relative contributions from the triceps surae and Achilles tendon during conditions relevant to postural control. We used a novel technique that combines B-mode ultrasound imaging with joint-level perturbations to quantify ankle, muscle and tendon impedance simultaneously across activation levels from 0% to 30% of maximum voluntary contraction. We found that muscle and tendon stiffness, the static component of impedance, increased with voluntary plantarflexion contractions, but that muscle stiffness exceeded tendon stiffness at very low loads (21±7 N). Above these loads, corresponding to 1.3% of maximal strength for an average participant in our study, ankle stiffness was determined predominately by Achilles tendon stiffness. At approximately 20% MVC for an average participant, ankle stiffness was 4 times more sensitive to changes in tendon stiffness than to changes in muscle stiffness. We provide the first empirical evidence demonstrating that the nervous system, through changes in muscle activations, leverages the non-linear properties of the Achilles tendon to increase ankle stiffness during postural conditions.

A motor plan is accessible for voluntary initiation and involuntary triggering at similar short latencies.

Movement goals are an essential component of motor planning, altering voluntary and involuntary motor actions. While there have been many studies of motor planning, it is unclear if motor goals influence voluntary and involuntary movements at similar latencies. The objectives of this study were to determine how long it takes to prepare a motor action and to compare this time for voluntary and involuntary movements. We hypothesized a prepared motor action would influence voluntarily and involuntarily initiated movements at the same latency. We trained subjects to reach with a forced reaction time paradigm and used a startling acoustic stimulus (SAS) to trigger involuntary initiation of the same reaches. The time available to prepare was controlled by varying when one of four reach targets was presented. Reach direction was used to evaluate accuracy. We quantified the time between target presentation and the cue or trigger for movement initiation. We found that reaches were accurately initiated when the target was presented 48 ms before the SAS and 162 ms before the cue to voluntarily initiate movement. While the SAS precisely controlled the latency of movement onset, voluntary reach onset was more variable. We, therefore, quantified the time between target presentation and movement onset and found no significant difference in the time required to plan reaches initiated voluntarily or involuntarily (∆ = 8 ms, p = 0.2). These results demonstrate that the time required to plan accurate reaches is similar regardless of if they are initiated voluntarily or triggered involuntarily. This finding may inform the understanding of neural pathways governing storage and access of motor plans.

Stretch reflex gain scaling at the shoulder varies with synergistic muscle activity.

The unique anatomy of the shoulder allows for expansive mobility but also sometimes precarious stability. It has long been suggested that stretch-sensitive reflexes contribute to maintaining joint stability through feedback control, but little is known about how stretch-sensitive reflexes are coordinated between the muscles of the shoulder. The purpose of this study was to investigate the coordination of stretch reflexes in shoulder muscles elicited by rotations of the glenohumeral joint. We hypothesized that stretch reflexes are sensitive to not only a given muscle's background activity but also the aggregate activity of all muscles crossing the shoulder based on the different groupings of muscles required to actuate the shoulder in three rotational degrees of freedom. We examined the relationship between a muscle's background activity and its reflex response in eight shoulder muscles by applying rotational perturbations while participants produced voluntary isometric torques. We found that this relationship, defined as gain scaling, differed at both short and long latencies based on the direction of voluntary torque generated by the participant. Therefore, gain scaling differed based on the aggregate of muscles that were active, not just the background activity in the muscle within which the reflex was measured. Across all muscles, the consideration of torque-dependent gain scaling improved model fits (ΔR2) by 0.17 ± 0.12. Modulation was most evident when volitional torques and perturbation directions were aligned along the same measurement axis, suggesting a functional role in resisting perturbations among synergists while maintaining task performance.NEW & NOTEWORTHY Careful coordination of muscles crossing the shoulder is needed to maintain the delicate balance between the joint's mobility and stability. We provide experimental evidence that stretch reflexes within shoulder muscles are modulated based on the aggregate activity of muscles crossing the joint, not just the activity of the muscle in which the reflex is elicited. Our results reflect coordination through neural coupling that may help maintain shoulder stability during encounters with environmental perturbations.

Estimating the dimensionality of the manifold underlying multi-electrode neural recordings.

It is generally accepted that the number of neurons in a given brain area far exceeds the number of neurons needed to carry any specific function controlled by that area. For example, motor areas of the human brain contain tens of millions of neurons that control the activation of tens or at most hundreds of muscles. This massive redundancy implies the covariation of many neurons, which constrains the population activity to a low-dimensional manifold within the space of all possible patterns of neural activity. To gain a conceptual understanding of the complexity of the neural activity within a manifold, it is useful to estimate its dimensionality, which quantifies the number of degrees of freedom required to describe the observed population activity without significant information loss. While there are many algorithms for dimensionality estimation, we do not know which are well suited for analyzing neural activity. The objective of this study was to evaluate the efficacy of several representative algorithms for estimating the dimensionality of linearly and nonlinearly embedded data. We generated synthetic neural recordings with known intrinsic dimensionality and used them to test the algorithms' accuracy and robustness. We emulated some of the important challenges associated with experimental data by adding noise, altering the nature of the embedding of the low-dimensional manifold within the high-dimensional recordings, varying the dimensionality of the manifold, and limiting the amount of available data. We demonstrated that linear algorithms overestimate the dimensionality of nonlinear, noise-free data. In cases of high noise, most algorithms overestimated the dimensionality. We thus developed a denoising algorithm based on deep learning, the "Joint Autoencoder", which significantly improved subsequent dimensionality estimation. Critically, we found that all algorithms failed when the intrinsic dimensionality was high (above 20) or when the amount of data used for estimation was low. Based on the challenges we observed, we formulated a pipeline for estimating the dimensionality of experimental neural data.

No Strength Differences Despite Greater Posterior Rotator Cuff Intramuscular Fat in Patients With Eccentric Glenohumeral Osteoarthritis.

BACKGROUND: When nonoperative measures do not alleviate the symptoms of glenohumeral osteoarthritis (OA), patients with advanced OA primarily are treated with anatomic total shoulder arthroplasty (TSA). It is unknown why TSAs performed in patients with eccentric (asymmetric glenoid wear) compared with concentric (symmetric glenoid wear) deformities exhibit higher failure rates, despite surgical advances. Persistent disruption of the posterior-to-anterior rotator cuff (RC) force couple resulting from posterior RC intramuscular degeneration in patients with eccentric deformities could impair external rotation strength and may contribute to eventual TSA failure. Pain and intramuscular fat within the RC muscles may impact external rotation strength measures and are important to consider. QUESTIONS/PURPOSES: (1) Is there relative shoulder external rotation weakness in patients with eccentric compared with concentric deformities? (2) Is there higher resting or torque-dependent pain in patients with eccentric compared with concentric deformities? (3) Do patients with eccentric deformities have higher posterior-to-anterior RC intramuscular fat percent ratios than patients with concentric deformities? METHODS: From February 2020 to November 2021, 65% (52 of 80) of patients with OA met study eligibility criteria. Of these, 63% (33 of 52) of patients enrolled and provided informed consent. From a convenience sample of 21 older adults with no history of shoulder pain, 20 met eligibility criteria as control participants. Of the convenience sample, 18 patients enrolled and provided informed consent. In total for this prospective, cross-sectional study, across patients with OA and control participants, 50% (51 of 101) of participants were enrolled and allocated into the eccentric (n = 16), concentric (n = 17), and control groups (n = 18). A 3-degree-of-freedom load cell was used to sensitively quantify strength in all three dimensions surrounding the shoulder. Participants performed maximal isometric contractions in 26 1-, 2-, and 3-degree-of-freedom direction combinations involving adduction/abduction, internal/external rotation, and/or flexion/extension. To test for relative external rotation weakness, we quantified relative strength in opposing directions (three-dimensional [3D] strength balance) along the X (+adduction/-abduction), Y (+internal/-external rotation), and Z (+flexion/-extension) axes and compared across the three groups. Patients with OA rated their shoulder pain (numerical rating 0-10) before testing at rest (resting pain; response to "How bad is your pain today?") and with each maximal contraction (torque-dependent pain; numerical rating 0-10). Resting and torque-dependent pain were compared between patients with eccentric and concentric deformities to determine if pain was higher in the eccentric group. The RC cross-sectional areas and intramuscular fat percentages were quantified on Dixon-sequence MRIs by a single observer who performed manual segmentation using previously validated methods. Ratios of posterior-to-anterior RC fat percent (infraspinatus + teres minor fat percent/subscapularis fat percent) were computed and compared between the OA groups. RESULTS: There was no relative external rotation weakness in patients with eccentric deformities (Y component of 3D strength balance, mean ± SD: -4.7% ± 5.1%) compared with patients with concentric deformities (-0.05% ± 4.5%, mean difference -4.7% [95% CI -7.5% to -1.9%]; p = 0.05). However, there was more variability in 3D strength balance in the eccentric group (95% CI volume, % 3 : 893) compared with the concentric group (95% CI volume, % 3 : 579). In patients with eccentric compared with concentric deformities, there was no difference in median (IQR) resting pain (1.0 [3.0] versus 2.0 [2.3], mean rank difference 4.5 [95% CI -6.6 to 16]; p = 0.61) or torque-dependent pain (0.70 [3.0] versus 0.58 [1.5], mean rank difference 2.6 [95% CI -8.8 to 14]; p = 0.86). In the subset of 18 of 33 patients with OA who underwent MRI, seven patients with eccentric deformities demonstrated a higher posterior-to-anterior RC fat percent ratio than the 11 patients with concentric deformities (1.2 [0.8] versus 0.70 [0.3], mean rank difference 6.4 [95% CI 1.4 to 11.5]; p = 0.01). CONCLUSION: Patients with eccentric deformities demonstrated higher variability in strength compared with patients with concentric deformities. This increased variability suggests patients with potential subtypes of eccentric wear patterns (posterior-superior, posterior-central, and posterior-inferior) may compensate differently for underlying anatomic changes by adopting unique kinematic or muscle activation patterns. CLINICAL RELEVANCE: Our findings highlight the importance of careful clinical evaluation of patients presenting with eccentric deformities because some may exhibit potentially detrimental strength deficits. Recognition of such strength deficits may allow for targeted rehabilitation. Future work should explore the relationship between strength in patients with specific subtypes of eccentric wear patterns and potential forms of kinematic or muscular compensation to determine whether these factors play a role in TSA failures in patients with eccentric deformities.

Cancer survivors post-chemotherapy exhibit unique proprioceptive deficits in proximal limbs.

BACKGROUND: Oxaliplatin (OX) chemotherapy for colorectal cancer is associated with adverse neurotoxic effects that can contribute to long-term sensorimotor impairments in cancer survivors. It is often thought that the sensorimotor impairments are dominated by OX-induced dying-back sensory neuropathy that primarily affects the distal regions of the limb. Recent preclinical studies have identified encoding dysfunction of muscle proprioceptors as an alternative mechanism. Unlike the dying-back sensory neuropathy affecting distal limbs, dysfunction of muscle proprioceptors could have more widespread effects. Most investigations of chemotherapy-induced sensorimotor impairments have considered only the effects of distal changes in sensory processing; none have evaluated proximal changes or their influence on function. Our study fills this gap by evaluating the functional use of proprioception in the shoulder and elbow joints of cancer survivors post OX chemotherapy. We implemented three multidirectional sensorimotor tasks: force matching, target reaching, and postural stability tasks to evaluate various aspects of proprioception and their use. Force and kinematic data of the sensorimotor tasks were collected in 13 cancer survivors treated with OX and 13 age-matched healthy controls. RESULTS: Cancer survivors exhibited less accuracy and precision than an age-matched control group when they had to rely only on proprioceptive information to match force, even for forces that required only torques about the shoulder. There were also small differences in the ability to maintain arm posture but no significant differences in reaching. The force deficits in cancer survivors were significantly correlated with self-reported motor dysfunction. CONCLUSIONS: These results suggest that cancer survivors post OX chemotherapy exhibit proximal proprioceptive deficits, and that the deficits in producing accurate and precise forces are larger than those for producing unloaded movements. Current clinical assessments of chemotherapy-related sensorimotor dysfunction are largely limited to distal symptoms. Our study suggests that we also need to consider changes in proximal function. Force matching tasks similar to those used here could provide a clinically meaningful approach to quantifying OX-related movement dysfunction during and after chemotherapy.

A review of movement disorders in chemotherapy-induced neurotoxicity.

Chemotherapy agents used in the standard treatments for many types of cancer are neurotoxic and can lead to lasting sensory and motor symptoms that compromise day-to-day movement functions in cancer survivors. To date, the details of movement disorders associated with chemotherapy are known largely through self-reported symptoms and functional limitations. There are few quantitative studies of specific movement deficits, limiting our understanding of dysfunction, as well as effective assessments and interventions. The aim of this narrative review is to consolidate the current understanding of sensorimotor disabilities based on quantitative measures in cancer survivors who received chemotherapy. We performed literature searches on PubMed and found 32 relevant movement studies. We categorized these studies into three themes based on the movement deficits investigated: (1) balance and postural control; (2) gait function; (3) upper limb function. This literature suggests that cancer survivors have increased postural sway, more conservative gait patterns, and suboptimal hand function compared to healthy individuals. More studies are needed that use objective measures of sensorimotor function to better characterize movement disabilities and investigate the underlying causes, as required for developing targeted assessments and interventions. By updating our understanding of movement impairments in this population, we identify significant gaps in knowledge that will help guide the direction of future research.

A muscle-activity-dependent gain between motor cortex and EMG.

Whether one is delicately placing a contact lens on the surface of the eye or lifting a heavy weight from the floor, the motor system must produce a wide range of forces under different dynamical loads. How does the motor cortex, with neurons that have a limited activity range, function effectively under these widely varying conditions? In this study, we explored the interaction of activity in primary motor cortex (M1) and muscles (electromyograms, EMGs) of two male rhesus monkeys for wrist movements made during three tasks requiring different dynamical loads and forces. Despite traditionally providing adequate predictions in single tasks, in our experiments, a single linear model failed to account for the relation between M1 activity and EMG across conditions. However, a model with a gain parameter that increased with the target force remained accurate across forces and dynamical loads. Surprisingly, this model showed that a greater proportion of EMG changes were explained by the nonlinear gain than the linear mapping from M1. In addition to its theoretical implications, the strength of this nonlinearity has important implications for brain-computer interfaces (BCIs). If BCI decoders are to be used to control movement dynamics (including interaction forces) directly, they will need to be nonlinear and include training data from broad data sets to function effectively across tasks. Our study reinforces the need to investigate neural control of movement across a wide range of conditions to understand its basic characteristics as well as translational implications. NEW & NOTEWORTHY We explored the motor cortex-to-electromyogram (EMG) mapping across a wide range of forces and loading conditions, which we found to be highly nonlinear. A greater proportion of EMG was explained by a nonlinear gain than a linear mapping. This nonlinearity allows motor cortex to control the wide range of forces encountered in the real world. These results unify earlier observations and inform the next-generation brain-computer interfaces that will control movement dynamics and interaction forces.

Uncertainty in when a perturbation will arrive influences the preparation and release of triggered responses.

The timing and magnitude of muscle responses to perturbations are critical for acting in uncertain environments. A planned movement can strongly influence average muscle responses to perturbations, but certainty in when a perturbation will arrive changes this effect. The objective of this study was to investigate how uncertainty in perturbation timing influences the preparation and release of involuntary, perturbation-triggered responses. We hypothesized that uncertainty would influence the average magnitude of triggered responses and how they develop in time. We investigated three levels of uncertainty in when a proprioceptive cue to move would arrive by changing the duration and variability of the time between a preparation and movement cue. Participants performed ballistic elbow extension movements in response to the movement cue. Unexpected, large perturbations that flexed the elbow were delivered at various times between the preparation and movement cues to evaluate how cue uncertainty influenced the development of triggered responses. We found that this uncertainty strongly influences how a motor response is prepared, and the efficacy of triggering that response by a postural perturbation. When timing was certain, the motor plan was prepared within 150 ms of the expected disturbance, and consistently released earlier by a perturbation than could be done voluntarily. Less predictable stimuli led to much earlier planning and a lower probability of releasing the plan early. These results clarify how uncertainty in when to move influences the planning and early release of perturbation-triggered responses, demonstrating an effect similar to previous reports on the planning of volitional movements.

Mechanisms contributing to reduced knee stiffness during movement.

The ability to modulate the mechanical properties of our limbs contributes to our ability to interact with the physical world in a consistent and predictable manner. An individual joint's contributions to whole limb mechanics can be quantified by its joint impedance, which characterizes the torque generated about a joint in response to external perturbations of position. A number of studies have estimated joint impedance during movement and have shown that it can be much lower than it is during posture. However, the mechanisms contributing to these differences remain unknown partly because conditions known to affect impedance, including muscle activation and joint angles, have not been carefully controlled across studies. The goal of this study was to contrast knee impedance during continuous volitional movements with that during maintained postures spanning a similar range of joint angles and muscle activations and to explore physiological mechanisms likely to contribute to the observed differences. We found that knee impedance was substantially lower during movement than during matched postural tasks, even for matched muscle activations. At times, the impedance during movement was even lower than that measured during isometric tasks with no volitional muscle activity. These decreases in impedance could be attributed in part to reduced stretch reflexes during movement and to an effect of movement itself on reducing knee impedance.

Consequences of biomechanically constrained tasks in the design and interpretation of synergy analyses.

Matrix factorization algorithms are commonly used to analyze muscle activity and provide insight into neuromuscular control. These algorithms identify low-dimensional subspaces, commonly referred to as synergies, which can describe variation in muscle activity during a task. Synergies are often interpreted as reflecting underlying neural control; however, it is unclear how these analyses are influenced by biomechanical and task constraints, which can also lead to low-dimensional patterns of muscle activation. The aim of this study was to evaluate whether commonly used algorithms and experimental methods can accurately identify synergy-based control strategies. This was accomplished by evaluating synergies from five common matrix factorization algorithms using muscle activations calculated from 1) a biomechanically constrained task using a musculoskeletal model and 2) without task constraints using random synergy activations. Algorithm performance was assessed by calculating the similarity between estimated synergies and those imposed during the simulations; similarities ranged from 0 (random chance) to 1 (perfect similarity). Although some of the algorithms could accurately estimate specified synergies without biomechanical or task constraints (similarity >0.7), with these constraints the similarity of estimated synergies decreased significantly (0.3-0.4). The ability of these algorithms to accurately identify synergies was negatively impacted by correlation of synergy activations, which are increased when substantial biomechanical or task constraints are present. Increased variability in synergy activations, which can be captured using robust experimental paradigms that include natural variability in motor activation patterns, improved identification accuracy but did not completely overcome effects of biomechanical and task constraints. These results demonstrate that a biomechanically constrained task can reduce the accuracy of estimated synergies and highlight the importance of using experimental protocols with physiological variability to improve synergy analyses.

Arm dominance affects feedforward strategy more than feedback sensitivity during a postural task.

Handedness is a feature of human motor control that is still not fully understood. Recent work has demonstrated that the dominant and nondominant arm each excel at different behaviors and has proposed that this behavioral asymmetry arises from lateralization in the cerebral cortex: the dominant side specializes in predictive trajectory control, while the nondominant side is specialized for impedance control. Long-latency stretch reflexes are an automatic mechanism for regulating posture and have been shown to contribute to limb impedance. To determine whether long-latency reflexes also contribute to asymmetric motor behavior in the upper limbs, we investigated the effect of arm dominance on stretch reflexes during a postural task that required varying degrees of impedance control. Our results demonstrated slightly but significantly larger reflex responses in the biarticular muscles of the nondominant arm, as would be consistent with increased impedance control. These differences were attributed solely to higher levels of voluntary background activity in the nondominant biarticular muscles, indicating that feedforward strategies for postural stability may differ between arms. Reflex sensitivity, which was defined as the magnitude of the reflex response for matched levels of background activity, was not significantly different between arms for a broad subject population ranging from 23 to 51 years of age. These results indicate that inter-arm differences in feedforward strategies are more influential during posture than differences in feedback sensitivity, in a broad subject population. Interestingly, restricting our analysis to subjects under 40 years of age revealed a small increase in long-latency reflex sensitivity in the nondominant arm relative to the dominant arm. Though our subject numbers were small for this secondary analysis, it suggests that further studies may be required to assess the influence of reflex lateralization throughout development.

Withdrawal reflexes in the upper limb adapt to arm posture and stimulus location.

INTRODUCTION: Withdrawal reflexes in the leg adapt in a context-appropriate manner to remove the limb from noxious stimuli, but the extent to which withdrawal reflexes adapt in the arm remains unknown. METHODS: We examined the adaptability of withdrawal reflexes in response to nociceptive stimuli applied in different arm postures and to different digits. Reflexes were elicited at rest, and kinetic and electromyographic responses were recorded under isometric conditions, thereby allowing motorneuron pool excitability to be controlled. RESULTS: Endpoint force changed from a posterior-lateral direction in a flexed posture to predominantly a posterior direction in a more extended posture [change in force angle (mean ± standard deviation) 35.6 ± 5.0°], and the force direction changed similarly with digit I stimulation compared with digit V (change = 22.9 ± 2.9°). CONCLUSIONS: The withdrawal reflex in the human upper limb adapts in a functionally relevant manner when elicited at rest.

Aging Does Not Alter Ankle, Muscle, and Tendon Stiffness at Low Loads Relevant to Stance.

Older adults have difficulty maintaining balance when faced with postural disturbances, a task that is influenced by the stiffness of the triceps surae and Achilles tendon. Age-related changes in Achilles tendon stiffness have been reported at matched levels of effort, but measures typically have not been made at matched loads, which is important due to age-dependent changes in strength. Moreover, there has been limited investigation into age-dependent changes in muscle stiffness. Here, we investigate how age alters muscle and tendon stiffness and their influence on ankle stiffness. We hypothesized that age-related changes in muscle and tendon contribute to reduced ankle stiffness in older adults and evaluated this hypothesis when either load or effort were matched. We used B-mode ultrasound with joint-level perturbations to quantify ankle, muscle, and tendon stiffness across a range of loads and efforts in seventeen healthy younger and older adults. At matched loads relevant to standing and the stance phase of walking, there was no significant difference in ankle, muscle, or tendon stiffness between groups (all p > 0.13). However, at matched effort, older adults exhibited a significant decrease in ankle (27%; p = 0.008), muscle (37%; p = 0.02), and tendon stiffness (22%; p = 0.03) at 30% of maximum effort. This is consistent with our finding that older adults were 36% weaker than younger adults in plantarflexion (p = 0.004). Together, these results indicate that, at the loads tested in this study, there are no age-dependent changes in the mechanical properties of muscle or tendon, only differences in strength that result in altered ankle, muscle, and tendon stiffness at matched levels of effort.

The Simultaneous Model-Based Estimation of Joint, Muscle, and Tendon Stiffness is Highly Sensitive to the Tendon Force-Strain Relationship.

OBJECTIVE: Accurate estimation of stiffness across anatomical levels (i.e., joint, muscle, and tendon) in vivo has long been a challenge in biomechanics. Recent advances in electromyography (EMG)-driven musculoskeletal modeling have allowed the non-invasive estimation of stiffness during dynamic joint rotations. Nevertheless, validation has been limited to the joint level due to a lack of simultaneous in vivo experimental measurements of muscle and tendon stiffness. METHODS: With a focus on the triceps surae, we employed a novel perturbation-based experimental technique informed by dynamometry and ultrasonography to derive reference stiffness at the joint, muscle, and tendon levels simultaneously. Here, we propose a new EMG-driven model-based approach that does not require external joint perturbation, nor ultrasonography, to estimate multi-level stiffness. We present a novel set of closed-form equations that enables the person-specific tuning of musculoskeletal parameters dictating biological stiffness, including passive force-length relationships in modeled muscles and tendons. RESULTS: Calibrated EMG-driven musculoskeletal models estimated the reference data with average normalized root-mean-square error ≈ 20%. Moreover, only when calibrated tendons were approximately four times more compliant than typically modeled, our approach could estimate multi-level reference stiffness. CONCLUSION: EMG-driven musculoskeletal models can be calibrated on a larger set of reference data to provide more realistic values for the biomechanical variables across multiple anatomical levels. Moreover, the tendon models that are typically used in musculoskeletal modeling are too stiff. SIGNIFICANCE: Calibrated musculoskeletal models informed by experimental measurements give access to an augmented range of biomechanical variables that might not be easily measured with sensors alone.

Older age is associated with decreased overall shoulder strength but not direction-specific differences in the three-dimensional feasible torque space.

Shoulder strength is reduced in older adults but has only been assessed in planar motions that do not reflect the diverse requirements of daily tasks. We quantified the impact of age on strength spanning the three degrees of freedom relevant to shoulder function, referred to as the feasible torque space. We hypothesized that the feasible torque space would differ with age and expected this age-effect to reflect direction-specific deficits. We measured strength in 32 directions to characterize the feasible torque space of the shoulder in participants without shoulder pain or tendinous pathology (n = 39, 19-86 years). We modeled the feasible torque space for each participant as an ellipsoid, computed the ellipsoid size and direction-specific metrics (ellipsoid position, orientation, and shape), and then tested the effect of age on each metric. Age was negatively associated with ellipsoid size (a measure of overall strength magnitude; -0.0033 ± 0.0007 (Nm/kg)/year, p < 0.0001). Contrary to our expectation, the effect of age on the direction-specific metrics did not reach statistical significance. The effect of age did not differ significantly between male and female participants. Three-dimensional strength measurements allowed us to constrain the direction of participants' maximum torque production and characterize the entire feasible torque space. Our findings support a generalized shoulder strengthening program to address age-related shoulder weakness in those without pain or pathology. Clinical exam findings of imbalanced weakness may suggest underlying pathology beyond an effect of age. Longitudinal studies are needed to determine the positive or negative impact of our results.

External Rotation Strength After TSA in Osteoarthritic Shoulders with Eccentric Deformity Is Not Impacted by Posterior Rotator Cuff Deficiency.

Background: Patients with persistent glenohumeral osteoarthritis symptoms despite nonoperative management may pursue anatomic total shoulder arthroplasty (TSA). TSA revision rates are higher in patients with preoperative eccentric (asymmetric posterior erosion) compared with concentric (symmetric) glenoid deformity. If posterior rotator cuff deficiency demonstrated preoperatively in patients with eccentric deformity persists after TSA, it may manifest as relative weakness in external compared with internal rotation secondary to deficient activity of the shoulder external rotator muscles. Persistent posterior rotator cuff deficiency is hypothesized to contribute to TSA failures. However, it remains unknown whether rotational strength is impaired after TSA in patients with eccentric deformity. Our goal was to determine if patients with eccentric deformity exhibit relative external rotation weakness that may be explained by posterior rotator cuff deficiency after TSA. Methods: Patients who were >1 year after TSA for primary glenohumeral osteoarthritis and had had preoperative eccentric or concentric deformity were prospectively recruited. Torque was measured and electromyography was performed during maximal isometric contractions in 26 three-dimensional direction combinations. Relative strength in opposing directions (strength balance) and muscle activity of 6 shoulder rotators were compared between groups. Results: The internal (+) and external (-) rotation component of strength balance did not differ in patients with eccentric (mean internal-external rotation component of strength balance: -7.6% ± 7.4%) compared with concentric deformity (-10.3% ± 6.8%) (mean difference: 2.7% [95% confidence interval (CI), -1.3% to 6.7%]; p = 0.59), suggesting no relative external rotation weakness. Infraspinatus activity was reduced in patients with eccentric (43.9% ± 10.4% of maximum voluntary contraction [MVC]) compared with concentric (51.3% ± 10.4% of MVC) deformity (mean difference: -7.4% [95% CI, -13.4% to -1.4%] of MVC; p = 0.04). Conclusions: A relative external rotation strength deficit following TSA was not found, despite evidence of reduced infraspinatus activity, in the eccentric-deformity group. Reduced infraspinatus activity suggests that posterior rotator cuff deficiencies may persist following TSA in patients with eccentric deformities. Longitudinal study is necessary to evaluate muscle imbalance as a contributor to higher TSA failure rates. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Grand Challenges at the Interface of Engineering and Medicine.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating "avatars" (herein defined as an extension of "digital twins") of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.