A patient-centered 'test-drive' strategy for ankle-foot orthosis prescription: Protocol for a randomized participant-blinded trial.

BACKGROUND: Ankle-foot orthoses (AFOs) are commonly used to overcome mobility limitations related to lower limb musculoskeletal injury. Despite a multitude of AFOs to choose from, there is scant evidence to guide AFO prescription and limited opportunities for AFO users to provide experiential input during the process. To address these limitations in the current prescription process, this study evaluates a novel, user-centered and personalized 'test-drive' strategy using a robotic exoskeleton ('AFO emulator') to emulate commercial AFO mechanical properties (i.e., stiffness). The study will determine if brief, in-lab trials (with emulated or actual AFOs) can predict longer term preference, satisfaction, and mobility outcomes after community trials (with the actual AFOs). Secondarily, it will compare the in-lab experience of walking between actual vs. emulated AFOs. METHODS AND ANALYSIS: In this participant-blinded, randomized crossover study we will recruit up to fifty-eight individuals with lower limb musculoskeletal injuries who currently use an AFO. Participants will walk on a treadmill with three actual AFOs and corresponding emulated AFOs for the "in-lab" assessments. For the community trial assessment, participants will wear each of the actual AFOs for a two-week period during activities of daily living. Performance-based and user-reported measures of preference and mobility will be compared between short- and long-term trials (i.e., in-lab vs. two-week community trials), and between in-lab trials (emulated vs. actual AFOs). TRIAL REGISTRATION: The study was prospectively registered at www.clininicaltrials.gov (Clinical Trials Study ID: NCT06113159). Date: November 1st 2023. https://classic.clinicaltrials.gov/ct2/show/NCT06113159.

Compromised neuromuscular function of walking in people with diabetes: A narrative review.

AIM: This review summarizes recent studies that have investigated the neuromuscular dysfunction of walking in people with diabetes and its relationship to ulcer formation. METHODS: A comprehensive electronic search in the database (Scopus, Web of Science, PsycINFO, ProQuest, and PubMed) was performed for articles pertaining to diabetes and gait biomechanics. RESULTS: The Achilles tendon is thicker and stiffer in those with diabetes. People with diabetes demonstrate changes in walking kinematics and kinetics, including slower self-selected gait speed, shorter stride length, longer stance phase duration, and decreased ankle, knee, and metatarsophalangeal (MTP) joint range of motion. EMG is altered during walking and may reflect diabetes-induced changes in muscle synergies. Synergies are notable because they provide a more holistic pattern of muscle activations and can help develop better tools for characterizing disease progression. CONCLUSION: Diabetes compromises neuromuscular coordination and function. The mechanisms contributing to ulcer formation are incompletely understood. Diabetes-related gait impairments may be a significant independent risk factor for the development of foot ulcers.

Comparison of five different methodologies for evaluating ankle-foot orthosis stiffness.

BACKGROUND: The mechanical properties of an ankle-foot orthosis (AFO) play an important role in the gait mechanics of the end user. However, testing methodologies for evaluating these mechanical properties are not standardized. The purpose of this study was to compare five different evaluation frameworks to assess AFO stiffness. METHOD: The same 13 carbon composite AFOs were tested with five different methods. Four previously reported custom test fixtures (the BRUCE, KST, SMApp, and EMPIRE) rotated an AFO into dorsiflexion about a defined axis in the sagittal plane. The fifth method involved quasi-static deflection of AFOs into dorsiflexion by hanging weights (HW) from the footplate. AFO rotational stiffness was calculated as the linear fit of the AFO resistive torque and angular deflection. Differences between methods were assessed using descriptive statistics and a repeated measures Friedman with post-hoc Bonferroni-Holm adjusted Wilcoxon signed-rank tests. RESULTS: There were significant differences in measured AFO stiffnesses between test methods. Specifically, the BRUCE and HW methods measured lower stiffness than both the EMPIRE and the KST. Stiffnesses measured by the SMApp were not significantly different than any test method. Stiffnesses were lowest in the HW method, where motion was not constrained to a single plane. The median difference in absolute AFO stiffness across methods was 1.03 Nm/deg with a range of [0.40 to 2.35] Nm/deg. The median relative percent difference, measured as the range of measured stiffness from the five methods over the average measured stiffness was 62% [range 13% to 156%]. When the HW method was excluded, the four previously reported test fixtures produced a median difference in absolute AFO stiffness of 0.52 [range 0.38 to 2.17] Nm/deg with a relative percent difference between the methods of 27% [range 13% to 89%]. CONCLUSIONS: This study demonstrates the importance of developing mechanical testing standards, similar to those that exist for lower limb prosthetics. Lacking standardization, differences in methodology can result in large differences in measured stiffness, particularly for different constraints on motion. Non-uniform measurement practices may limit the clinical utility of AFO stiffness as a metric in AFO prescription and future research.

Uneven Treadmill Training for Rehabilitation of Lateral Ankle Sprains and Chronic Ankle Instability: Protocol for a Pragmatic Randomized Controlled Trial.

BACKGROUND: Lateral ankle sprains (LASs) are common injuries among military service members. Approximately 40% of individuals with an LAS progress to develop chronic ankle instability (CAI), a condition that results in substantial mechanical and neurophysiological impairment and activity limitation. Since proprioceptive and balance training improve functional outcomes and prevent secondary injury following LAS, they are recommended in clinical practice. Uneven treadmills are an innovative modality that challenge the sensorimotor system while performing an ecologically valid task simulating environments frequently encountered by service members with LAS and CAI. OBJECTIVE: The aim of this study is to evaluate whether the inclusion of uneven treadmill training in standard rehabilitation can improve clinical, functional, biomechanical, and patient-reported outcomes compared with the standard of care alone in service members with LAS and CAI. The prophylactic effects of treatment on secondary injury and identification of any contributing or mediating factors that influence outcomes following treatment will also be evaluated. We hypothesize that service members receiving uneven treadmill training will demonstrate greater improvements in clinical and instrumented measures of impairment, patient-reported function, and lower risk of injury recurrence than the control group immediately post and 18 months following treatment. METHODS: A multisite, parallel randomized clinical trial will be performed among service members aged 18-49 years being treated for LAS and CAI in military treatment facilities in the United States. Participants randomly assigned and allocated to receive the experimental intervention will be provided up to 12 sessions of training on an uneven terrain treadmill over a 6-week treatment course to supplement standard rehabilitation care. Treatment intensity of the rehabilitation exercises and treadmill training will be progressed on the basis of patient-perceived intensity and treatment responses. Outcome measures will include patient-reported outcomes, functional assessments, performance measures, and biomechanical measures. Investigators collecting outcome measures will be blinded to treatment allocation. Reinjury rates and patient-reported outcomes of function will be tracked over 18 months following treatment. RESULTS: The project was funded in September 2020. Patient recruitment began in November 2021, with 3 participants enrolled as of February 2022. Dissemination of the main study findings is anticipated in 2024. CONCLUSIONS: This study will assess the impact of an innovative uneven-terrain treadmill on treatment outcomes in the rehabilitation of service members with LAS and CAI. The results of this study will be used to inform rehabilitation practices and to potentially improve functional outcomes and secondary prevention in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04999904; https://clinicaltrials.gov/ct2/show/NCT04999904?term=NCT04999904. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38442.

Multiplanar Stiffness of Commercial Carbon Composite Ankle-Foot Orthoses.

The mechanical properties of an ankle-foot orthosis (AFO) can impact how a user's movement is either restricted or augmented by the device. However, standardized methods for assessing stiffness properties of AFOs are lacking, posing a challenge for comparing between devices and across vendors. Therefore, the purpose of this study was to quantify the rotational stiffness of thirteen commercial, nonarticulated, carbon composite ankle-foot orthoses. A custom, instrumented test fixture, for evaluating mechanical properties in rotating exoskeletons (EMPIRE), deflected an AFO through 20 deg of plantar/dorsiflexion motion about a specified, but adjustable, ankle axis. Sagittal, frontal, and transverse plane rotational stiffness were calculated, and reliability was assessed between cycles, sessions, and testers. The EMPIRE demonstrated good-to-excellent reliability between testers, sessions, and cycles (intraclass correlation coefficients all ≥0.95 for sagittal plane stiffness measures). Sagittal plane AFO stiffness ranged from 0.58 N·m/deg to 3.66 N·m/deg. AFOs with a lateral strut demonstrated frontal plane stiffnesses up to 0.71 N·m/deg of eversion while those with a medial strut demonstrated frontal plane stiffnesses up to 0.53 N·m/deg of inversion. Transverse plane stiffnesses were less than 0.30 N·m/deg of internal or external rotation. These results directly compare AFOs of different models and from different manufacturers using consistent methodology and are intended as a resource for clinicians in identifying a device with stiffness properties for individual patients.

Muscle synergy structure and gait patterns in children with spastic cerebral palsy.

AIM: To determine if muscle synergy structure (activations and weights) differs between gait patterns in children with spastic cerebral palsy (CP). METHOD: In this cross-sectional study, we classified 188 children with unilateral (n=82) or bilateral (n=106) spastic CP (mean age: 9y 5mo, SD: 4y 3mo, range: 3y 9mo-17y 7mo; 75 females; Gross Motor Function Classification System [GMFCS] level I: 106, GMFCS level II: 55, GMFCS level III: 27) into a minor deviations (n=34), drop foot (n=16), genu recurvatum (n=26), apparent equinus (n=53), crouch (n=39), and jump gait pattern (n=20). Surface electromyography recordings from eight lower limb muscles of the most affected side were used to calculate synergies with weighted non-negative matrix factorization. We compared synergy activations and weights between the patterns. RESULTS: Synergy structure was similar between gait patterns, although weights differed in the more impaired children (crouch and jump gait) when compared to the other patterns. Variability in synergy structure between participants was high. INTERPRETATION: The similarity in synergy structure between gait patterns suggests a generic motor control strategy to compensate for the brain lesion. However, the differences in weights and high variability between participants indicate that this generic motor control strategy might be individualized and dependent on impairment level.

Muscle weakness has a limited effect on motor control of gait in Duchenne muscular dystrophy.

AIM: Our aim was to determine if synergy weights and activations are altered in Duchenne muscular dystrophy (DMD) and if these alterations could be linked to muscle weakness. METHODS: In 22 children with DMD and 22 typical developing (TD) children of a similar age, surface electromyography (sEMG) of the gluteus medius, rectus femoris (REF), medial hamstrings, tibialis anterior, and medial gastrocnemius (GAS) were recorded during gait. Muscle weakness was assessed with maximal voluntary isometric contractions (MVIC). Synergies were calculated with non-negative matrix factorization. The number of synergies explaining ≥90% of the variance in the sEMG signals (N90), were extracted and grouped with k-means cluster analysis. We verified differences in weights with a Mann-Whitney U test. Statistical non-parametric mapping (Hotelling's T2 test and two-tailed t-test) was used to assess group differences in synergy activations. We used Spearman's rank correlation coefficients and canonical correlation analysis to assess if weakness was related to modifications in weights and activations, respectively. RESULTS: For both groups, average N90 was three. In synergy one, characterized by activity at the beginning of stance, the DMDs showed an increased REF weight (p = 0.001) and decreased GAS weight (p = 0.007). Synergy activations were similar, with only a small difference detected in mid-swing in the combined activations (p<0.001). Weakness was not associated with these differences. CONCLUSION: Despite the apparent weakness in DMD, synergy weights and activations were similar between the two groups. Our findings are in line with previous research suggesting non-neural alterations have limited influence on muscle synergies.

Muscle synergies demonstrate only minimal changes after treatment in cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) have altered synergies compared to typically-developing peers, reflecting different neuromuscular control strategies used to move. While these children receive a variety of treatments to improve gait, whether synergies change after treatment, or are associated with treatment outcomes, remains unknown. METHODS: We evaluated synergies for 147 children with CP before and after three common treatments: botulinum toxin type-A injection (n = 52), selective dorsal rhizotomy (n = 38), and multi-level orthopaedic surgery (n = 57). Changes in synergy complexity were measured by the number of synergies required to explain > 90% of the total variance in electromyography data and total variance accounted for by one synergy. Synergy weights and activations before and after treatment were compared using the cosine similarity relative to average synergies of 31 typically-developing (TD) peers. RESULTS: There were minimal changes in synergies after treatment despite changes in walking patterns. Number of synergies did not change significantly for any treatment group. Total variance accounted for by one synergy increased (i.e., moved further from TD peers) after botulinum toxin type-A injection (1.3%) and selective dorsal rhizotomy (1.9%), but the change was small. Synergy weights did not change for any treatment group (average 0.001 ± 0.10), but synergy activations after selective dorsal rhizotomy did change and were less similar to TD peers (- 0.03 ± 0.07). Only changes in synergy activations were associated with changes in gait kinematics or walking speed after treatment. Children with synergy activations more similar to TD peers after treatment had greater improvements in gait. CONCLUSIONS: While many of these children received significant surgical procedures and prolonged rehabilitation, the minimal changes in synergies after treatment highlight the challenges in altering neuromuscular control in CP. Development of treatment strategies that directly target impaired control or are optimized to an individual's unique control may be required to improve walking function.

Muscle Synergy Constraints Do Not Improve Estimates of Muscle Activity From Static Optimization During Gait for Unimpaired Children or Children With Cerebral Palsy.

Neuromusculoskeletal simulation provides a promising platform to inform the design of assistive devices or inform rehabilitation. For these applications, a simulation must be able to accurately represent the person of interest, such as an individual with a neurologic injury. If a simulation fails to predict how an individual recruits and coordinates their muscles during movement, it will have limited utility for informing design or rehabilitation. While inverse dynamic simulations have previously been used to evaluate anticipated responses from interventions, like orthopedic surgery or orthoses, they frequently struggle to accurately estimate muscle activations, even for tasks like walking. The simulated muscle activity often fails to represent experimentally measured muscle activity from electromyographic (EMG) recordings. Research has theorized that the nervous system may simplify the range of possible activations used during dynamic tasks, by constraining activations to weighted groups of muscles, referred to as muscle synergies. Synergies are altered after neurological injury, such as stroke or cerebral palsy (CP), and may provide a method for improving subject-specific models of neuromuscular control. The aim of this study was to test whether constraining simulation to synergies could improve estimated muscle activations compared to EMG data. We evaluated modeled muscle activations during gait for six typically developing (TD) children and six children with CP. Muscle activations were estimated with: (1) static optimization (SO), minimizing muscle activations squared, and (2) synergy SO (SynSO), minimizing synergy activations squared using the weights identified from EMG data for two to five synergies. While SynSO caused changes in estimated activations compared to SO, the correlation to EMG data was not higher in SynSO than SO for either TD or CP groups. The correlations to EMG were higher in CP than TD for both SO (CP: 0.48, TD: 0.36) and SynSO (CP: 0.46, TD: 0.26 for five synergies). Constraining activations to SynSO caused the simulated muscle stress to increase compared to SO for all individuals, causing a 157% increase with two synergies. These results suggest that constraining simulated activations in inverse dynamic simulations to subject-specific synergies alone may not improve estimation of muscle activations during gait for generic musculoskeletal models.

Repeatability of electromyography recordings and muscle synergies during gait among children with cerebral palsy.

BACKGROUND: Clinical gait analysis is commonly used in the evaluation and treatment of children with cerebral palsy (CP). While the repeatability of kinematic and kinetic measures of gait has previously been evaluated, the repeatability of electromyography (EMG) recordings or measures calculated from EMG data, such as muscle synergies, remains unclear for this population. RESEARCH QUESTION: Are EMG recordings and muscle synergies from clinical gait analysis repeatable between visits for children with CP? METHODS: We recruited 20 children with bilateral CP who had been referred for clinical gait analysis. The children completed two visits less than six weeks apart with EMG data collected bilaterally from five muscles (rectus femoris, medial hamstrings, vastus lateralis, anterior tibialis, and medial gastrocnemius). Variance ratio and cosine similarity were used to evaluate repeatability of EMG waveforms between visits. Nonnegative matrix factorization was used to calculate synergies from EMG data at each visit to compare synergy weights and activations. RESULTS & SIGNIFICANCE: The inter-visit variance ratios of EMG data for children with CP were similar to previously reported results for typically-developing children and unimpaired adults (range: 0.39 for vastus lateralis to 0.66 for rectus femoris). The average cosine similarity of the EMG waveforms between visits was greater than 0.9 for all muscles, while synergy weights and activations also had high similarity - greater than 0.8 and 0.9 between visits, respectively. These results demonstrate that EMG repeatability between visits during clinical gait analysis for children with CP is similar to unimpaired individuals. These results provide a baseline for evaluating whether observed changes in EMG recordings between visits reflect real changes in muscle activity or are within the range of inter-visit variability.

Associations Between Muscle Synergies and Treatment Outcomes in Cerebral Palsy Are Robust Across Clinical Centers.

OBJECTIVE: To determine whether patient-specific differences in motor control quantified using muscle synergy analysis were associated with changes in gait after treatment of cerebral palsy (CP) across 2 clinical centers with different treatments and clinical protocols. DESIGN: Retrospective cohort study. SETTING: Clinical medical center. PARTICIPANTS: Center 1: children with CP (n=473) and typically developing (TD) children (n=84). Center 2: children with CP (n=163) and TD children (n=12). INTERVENTIONS: Standard clinical care at each center. MAIN OUTCOME MEASURES: The Dynamic Motor Control Index During Walking (walk-DMC) was computed from electromyographic data during gait using muscle synergy analysis. Regression analysis was used to evaluate whether pretreatment walking speed or kinematics, muscle synergies, treatment group, prior treatment, or age were associated with posttreatment changes in gait at both clinical centers. RESULTS: Walk-DMC was significantly associated with changes in speed and kinematics after treatment with similar regression models at both centers. Children with less impaired motor control were more likely to have improvements in walking speed and gait kinematics after treatment, independent of treatment group. CONCLUSIONS: Dynamic motor control evaluated with synergy analysis was associated with changes in gait after treatment at both centers, despite differences in treatments and clinical protocols. This study further supports the finding that walk-DMC provides additional information, not captured in traditional gait analysis, that may be useful for treatment planning.

Non-neural Muscle Weakness Has Limited Influence on Complexity of Motor Control during Gait.

Cerebral palsy (CP) and Duchenne muscular dystrophy (DMD) are neuromuscular disorders characterized by muscle weakness. Weakness in CP has neural and non-neural components, whereas in DMD, weakness can be considered as a predominantly non-neural problem. Despite the different underlying causes, weakness is a constraint for the central nervous system when controlling gait. CP demonstrates decreased complexity of motor control during gait from muscle synergy analysis, which is reflected by a higher total variance accounted for by one synergy (tVAF1). However, it remains unclear if weakness directly contributes to higher tVAF1 in CP, or whether altered tVAF1 reflects mainly neural impairments. If muscle weakness directly contributes to higher tVAF1, then tVAF1 should also be increased in DMD. To examine the etiology of increased tVAF1, muscle activity data of gluteus medius, rectus femoris, medial hamstrings, medial gastrocnemius, and tibialis anterior were measured at self-selected walking speed, and strength data from knee extensors, knee flexors, dorsiflexors and plantar flexors, were analyzed in 15 children with CP [median (IQR) age: 8.9 (2.2)], 15 boys with DMD [8.7 (3.1)], and 15 typical developing (TD) children [8.6 (2.7)]. We computed tVAF1 from 10 concatenated steps with non-negative matrix factorization, and compared tVAF1 between the three groups with a Mann-Whiney U-test. Spearman's rank correlation coefficients were used to determine if weakness in specific muscle groups contributed to altered tVAF1. No significant differences in tVAF1 were found between DMD [tVAF1: 0.60 (0.07)] and TD children [0.65 (0.07)], while tVAF1 was significantly higher in CP [(0.74 (0.09)] than in the other groups (both p < 0.005). In CP, weakness in the plantar flexors was related to higher tVAF1 (r = -0.72). In DMD, knee extensor weakness related to increased tVAF1 (r = -0.50). These results suggest that the non-neural weakness in DMD had limited influence on complexity of motor control during gait and that the higher tVAF1 in children with CP is mainly related to neural impairments caused by the brain lesion.

Crouch severity is a poor predictor of elevated oxygen consumption in cerebral palsy.

Children with cerebral palsy (CP) expend more energy to walk compared to typically-developing peers. One of the most prevalent gait patterns among children with CP, crouch gait, is often singled out as especially exhausting. The dynamics of crouch gait increase external flexion moments and the demand on extensor muscles. This elevated demand is thought to dramatically increase energy expenditure. However, the impact of crouch severity on energy expenditure has not been investigated among children with CP. We evaluated oxygen consumption and gait kinematics for 573 children with bilateral CP. The average net nondimensional oxygen consumption during gait of the children with CP (0.18±0.06) was 2.9 times that of speed-matched typically-developing peers. Crouch severity was only modestly related to oxygen consumption, with measures of knee flexion angle during gait explaining only 5-20% of the variability in oxygen consumption. While knee moment and muscle activity were moderately to strongly correlated with crouch severity (r2=0.13-0.73), these variables were only weakly correlated with oxygen consumption (r2=0.02-0.04). Thus, although the dynamics of crouch gait increased muscle demand, these effects did not directly result in elevated energy expenditure. In clinical gait analysis, assumptions about an individual's energy expenditure should not be based upon kinematics or kinetics alone. Identifying patient-specific factors that contribute to increased energy expenditure may provide new pathways to improve gait for children with CP.

Muscle recruitment and coordination with an ankle exoskeleton.

Exoskeletons have the potential to assist and augment human performance. Understanding how users adapt their movement and neuromuscular control in response to external assistance is important to inform the design of these devices. The aim of this research was to evaluate changes in muscle recruitment and coordination for ten unimpaired individuals walking with an ankle exoskeleton. We evaluated changes in the activity of individual muscles, cocontraction levels, and synergistic patterns of muscle coordination with increasing exoskeleton work and torque. Participants were able to selectively reduce activity of the ankle plantarflexors with increasing exoskeleton assistance. Increasing exoskeleton net work resulted in greater reductions in muscle activity than increasing exoskeleton torque. Patterns of muscle coordination were not restricted or constrained to synergistic patterns observed during unassisted walking. While three synergies could describe nearly 95% of the variance in electromyography data during unassisted walking, these same synergies could describe only 85-90% of the variance in muscle activity while walking with the exoskeleton. Synergies calculated with the exoskeleton demonstrated greater changes in synergy weights with increasing exoskeleton work versus greater changes in synergy activations with increasing exoskeleton torque. These results support the theory that unimpaired individuals do not exclusively use central pattern generators or other low-level building blocks to coordinate muscle activity, especially when learning a new task or adapting to external assistance, and demonstrate the potential for using exoskeletons to modulate muscle recruitment and coordination patterns for rehabilitation or performance.

Electromyography Data Processing Impacts Muscle Synergies during Gait for Unimpaired Children and Children with Cerebral Palsy.

Muscle synergies calculated from electromyography (EMG) data identify weighted groups of muscles activated together during functional tasks. Research has shown that fewer synergies are required to describe EMG data of individuals with neurologic impairments. When considering potential clinical applications of synergies, understanding how EMG data processing impacts results and clinical interpretation is important. The aim of this study was to evaluate how EMG signal processing impacts synergy outputs during gait. We evaluated the impacts of two common processing steps for synergy analyses: low pass (LP) filtering and unit variance scaling. We evaluated EMG data collected during barefoot walking from five muscles of 113 children with cerebral palsy (CP) and 73 typically-developing (TD) children. We applied LP filters to the EMG data with cutoff frequencies ranging from 4 to 40 Hz (reflecting the range reported in prior synergy research). We also evaluated the impact of normalizing EMG amplitude by unit variance. We found that the total variance accounted for (tVAF) by a given number of synergies was sensitive to LP filter choice and decreased in both TD and CP groups with increasing LP cutoff frequency (e.g., 9.3 percentage points change for one synergy between 4 and 40 Hz). This change in tVAF can alter the number of synergies selected for further analyses. Normalizing tVAF to a z-score (e.g., dynamic motor control index during walking, walk-DMC) reduced sensitivity to LP cutoff. Unit variance scaling caused comparatively small changes in tVAF. Synergy weights and activations were impacted less than tVAF by LP filter choice and unit variance normalization. These results demonstrate that EMG signal processing methods impact outputs of synergy analysis and z-score based measures can assist in reporting and comparing results across studies and clinical centers.

Multistep model for predicting upper-limb 3D isometric force application from pre-movement electrocorticographic features.

Neural correlates of movement planning onset and direction may be present in human electrocorticography in the signal dynamics of both motor and non-motor cortical regions. We use a three-stage model of jPCA reduced-rank hidden Markov model (jPCA-RR-HMM), regularized shrunken-centroid discriminant analysis (RDA), and LASSO regression to extract direction-sensitive planning information and movement onset in an upper-limb 3D isometric force task in a human subject. This mode achieves a relatively high true positive force-onset prediction rate of 60% within 250ms, and an above-chance 36% accuracy (17% chance) in predicting one of six planned 3D directions of isometric force using pre-movement signals. We also find direction-distinguishing information up to 400ms before force onset in the pre-movement signals, captured by electrodes placed over the limb-ipsilateral dorsal premotor regions. This approach can contribute to more accurate decoding of higher-level movement goals, at earlier timescales, and inform sensor placement. Our results also contribute to further understanding of the spatiotemporal features of human motor planning.

Flow mechanotransduction regulates traction forces, intercellular forces, and adherens junctions.

Endothelial cells respond to fluid shear stress through mechanotransduction responses that affect their cytoskeleton and cell-cell contacts. Here, endothelial cells were grown as monolayers on arrays of microposts and exposed to laminar or disturbed flow to examine the relationship among traction forces, intercellular forces, and cell-cell junctions. Cells under laminar flow had traction forces that were higher than those under static conditions, whereas cells under disturbed flow had lower traction forces. The response in adhesion junction assembly matched closely with changes in traction forces since adherens junctions were larger in size for laminar flow and smaller for disturbed flow. Treating the cells with calyculin-A to increase myosin phosphorylation and traction forces caused an increase in adherens junction size, whereas Y-27362 cause a decrease in their size. Since tugging forces across cell-cell junctions can promote junctional assembly, we developed a novel approach to measure intercellular forces and found that these forces were higher for laminar flow than for static or disturbed flow. The size of adherens junctions and tight junctions matched closely with intercellular forces for these flow conditions. These results indicate that laminar flow can increase cytoskeletal tension while disturbed flow decreases cytoskeletal tension. Consequently, we found that changes in cytoskeletal tension in response to shear flow conditions can affect intercellular tension, which in turn regulates the assembly of cell-cell junctions.