Two motor neuron synergies, invariant across ankle joint angles, activate the triceps surae during plantarflexion.

Recent studies have suggested that the nervous system generates movements by controlling groups of motor neurons (synergies) that do not always align with muscle anatomy. In this study, we determined whether these synergies are robust across tasks with different mechanical constraints. We identified motor neuron synergies using principal component analysis (PCA) and cross-correlations between smoothed discharge rates of motor neurons. In part 1, we used simulations to validate these methods. The results suggested that PCA can accurately identify the number of common inputs and their distribution across active motor neurons. Moreover, the results confirmed that cross-correlation can separate pairs of motor neurons that receive common inputs from those that do not receive common inputs. In part 2, 16 individuals performed plantarflexion at three ankle angles while we recorded EMG signals from the gastrocnemius lateralis (GL) and medialis (GM) and the soleus (SOL) with grids of surface electrodes. The PCA revealed two motor neuron synergies. These motor neuron synergies were relatively stable, with no significant differences in the distribution of motor neuron weights across ankle angles (P = 0.62). When the cross-correlation was calculated for pairs of motor units tracked across ankle angles, we observed that only 13.0% of pairs of motor units from GL and GM exhibited significant correlations of their smoothed discharge rates across angles, confirming the low level of common inputs between these muscles. Overall, these results highlight the modularity of movement control at the motor neuron level, suggesting a sensible reduction of computational resources for movement control. KEY POINTS: The CNS might generate movements by activating groups of motor neurons (synergies) with common inputs. We show here that two main sources of common inputs drive the motor neurons innervating the triceps surae muscles during isometric ankle plantarflexions. We report that the distribution of these common inputs is globally invariant despite changing the mechanical constraints of the tasks, i.e. the ankle angle. These results suggest the functional relevance of the modular organization of the CNS to control movements.

Automatic Detection of Magnetic Disturbances in Magnetic Inertial Measurement Unit Sensors Based on Recurrent Neural Networks.

This paper proposes a new methodology for the automatic detection of magnetic disturbances from magnetic inertial measurement unit (MIMU) sensors based on deep learning. The proposed approach considers magnetometer data as input to a long short-term memory (LSTM) neural network and obtains a labeled time series output with the posterior probabilities of magnetic disturbance. We trained our algorithm on a data set that reproduces a wide range of magnetic perturbations and MIMU motions in a repeatable and reproducible way. The model was trained and tested using 15 folds, which considered independence in sensor, disturbance direction, and signal type. On average, the network can adequately detect the disturbances in 98% of the cases, which represents a significant improvement over current threshold-based detection algorithms.

Classification of Kinematic and Electromyographic Signals Associated with Pathological Tremor Using Machine and Deep Learning.

Peripheral Electrical Stimulation (PES) of afferent pathways has received increased interest as a solution to reduce pathological tremors with minimal side effects. Closed-loop PES systems might present some advantages in reducing tremors, but further developments are required in order to reliably detect pathological tremors to accurately enable the stimulation only if a tremor is present. This study explores different machine learning (K-Nearest Neighbors, Random Forest and Support Vector Machines) and deep learning (Long Short-Term Memory neural networks) models in order to provide a binary (Tremor; No Tremor) classification of kinematic (angle displacement) and electromyography (EMG) signals recorded from patients diagnosed with essential tremors and healthy subjects. Three types of signal sequences without any feature extraction were used as inputs for the classifiers: kinematics (wrist flexion-extension angle), raw EMG and EMG envelopes from wrist flexor and extensor muscles. All the models showed high classification scores (Tremor vs. No Tremor) for the different input data modalities, ranging from 0.8 to 0.99 for the f1 score. The LSTM models achieved 0.98 f1 scores for the classification of raw EMG signals, showing high potential to detect tremors without any processed features or preliminary information. These models may be explored in real-time closed-loop PES strategies to detect tremors and enable stimulation with minimal signal processing steps.

Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction.

INTRODUCTION: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. OBJECTIVE: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. METHODS: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. RESULTS: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. CONCLUSIONS: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

INTRODUCCIÓN: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. OBJETIVO: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. MÉTODOS: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. RESULTADOS: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. CONCLUSIONES: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

A unified scheme for the benchmarking of upper limb functions in neurological disorders.

BACKGROUND: In neurorehabilitation, we are witnessing a growing awareness of the importance of standardized quantitative assessment of limb functions. Detailed assessments of the sensorimotor deficits following neurological disorders are crucial. So far, this assessment has relied mainly on clinical scales, which showed several drawbacks. Different technologies could provide more objective and repeatable measurements. However, the current literature lacks practical guidelines for this purpose. Nowadays, the integration of available metrics, protocols, and algorithms into one harmonized benchmarking ecosystem for clinical and research practice is necessary. METHODS: This work presents a benchmarking framework for upper limb capacity. The scheme resulted from a multidisciplinary and iterative discussion among several partners with previous experience in benchmarking methodology, robotics, and clinical neurorehabilitation. We merged previous knowledge in benchmarking methodologies for human locomotion and direct clinical and engineering experience in upper limb rehabilitation. The scheme was designed to enable an instrumented evaluation of arm capacity and to assess the effectiveness of rehabilitative interventions with high reproducibility and resolution. It includes four elements: (1) a taxonomy for motor skills and abilities, (2) a list of performance indicators, (3) a list of required sensor modalities, and (4) a set of reproducible experimental protocols. RESULTS: We proposed six motor primitives as building blocks of most upper-limb daily-life activities and combined them into a set of functional motor skills. We identified the main aspects to be considered during clinical evaluation, and grouped them into ten motor abilities categories. For each ability, we proposed a set of performance indicators to quantify the proposed ability on a quantitative and high-resolution scale. Finally, we defined the procedures to be followed to perform the benchmarking assessment in a reproducible and reliable way, including the definition of the kinematic models and the target muscles. CONCLUSIONS: This work represents the first unified scheme for the benchmarking of upper limb capacity. To reach a consensus, this scheme should be validated with real experiments across clinical conditions and motor skills. This validation phase is expected to create a shared database of human performance, necessary to have realistic comparisons of treatments and drive the development of new personalized technologies.

Effects of gravity and kinematic constraints on muscle synergies in arm cycling.

Arm cycling is a bimanual motor task used in medical rehabilitation and in sports training. Understanding how muscle coordination changes across different biomechanical constraints in arm cycling is a step toward improved rehabilitation approaches. This exploratory study aims to get new insights on motor control during arm cycling. To achieve our main goal, we used the muscle synergies analysis to test three hypotheses: 1) body position with respect to gravity (sitting and supine) has an effect on muscle synergies; 2) the movement size (crank length) has an effect on the synergistic behavior; 3) the bimanual cranking mode (asynchronous and synchronous) requires different synergistic control. Thirteen able-bodied volunteers performed arm cranking on a custom-made device with unconnected cranks, which allowed testing three different conditions: body position (sitting vs. supine), crank length (10 cm vs. 15 cm), and cranking mode (synchronous vs. asynchronous). For each of the eight possible combinations, subjects cycled for 30 s while electromyography of eight muscles (four from each arm) were recorded: biceps brachii, triceps brachii, anterior deltoid, and posterior deltoid. Muscle synergies in this eight-dimensional muscle space were extracted by nonnegative matrix factorization. Four synergies accounted for over 90% of muscle activation variances in all conditions. Results showed that synergies were affected by body position and cranking mode but practically unaffected by movement size. These results suggest that the central nervous system may employ different motor control strategies in response to external constraints such as cranking mode and body position during arm cycling.NEW & NOTEWORTHY Recent studies analyzed muscle synergies in lower limb cycling. Here, we examine upper limb cycling and specifically the effect of body position with respect to gravity, movement size, and cranking mode on muscle coordination during arm cranking tasks. We show that altered body position and cranking mode affects modular organization of muscle activities. To our knowledge, this is the first study assessing motor control through muscle synergies framework during upper limb cycling with different constraints.

EEG hyperscanning in motor rehabilitation: a position paper.

Studying the human brain during interpersonal interaction allows us to answer many questions related to motor control and cognition. For instance, what happens in the brain when two people walking side by side begin to change their gait and match cadences? Adapted from the neuroimaging techniques used in single-brain measurements, hyperscanning (HS) is a technique used to measure brain activity from two or more individuals simultaneously. Thus far, HS has primarily focused on healthy participants during social interactions in order to characterize inter-brain dynamics. Here, we advocate for expanding the use of this electroencephalography hyperscanning (EEG-HS) technique to rehabilitation paradigms in individuals with neurological diagnoses, namely stroke, spinal cord injury (SCI), Parkinson's disease (PD), and traumatic brain injury (TBI). We claim that EEG-HS in patient populations with impaired motor function is particularly relevant and could provide additional insight on neural dynamics, optimizing rehabilitation strategies for each individual patient. In addition, we discuss future technologies related to EEG-HS that could be developed for use in the clinic as well as technical limitations to be considered in these proposed settings.

Human-machine-human interaction in motor control and rehabilitation: a review.

BACKGROUND: Human-human (HH) interaction mediated by machines (e.g., robots or passive sensorized devices), which we call human-machine-human (HMH) interaction, has been studied with increasing interest in the last decade. The use of machines allows the implementation of different forms of audiovisual and/or physical interaction in dyadic tasks. HMH interaction between two partners can improve the dyad's ability to accomplish a joint motor task (task performance) beyond either partner's ability to perform the task solo. It can also be used to more efficiently train an individual to improve their solo task performance (individual motor learning). We review recent research on the impact of HMH interaction on task performance and individual motor learning in the context of motor control and rehabilitation, and we propose future research directions in this area. METHODS: A systematic search was performed on the Scopus, IEEE Xplore, and PubMed databases. The search query was designed to find studies that involve HMH interaction in motor control and rehabilitation settings. Studies that do not investigate the effect of changing the interaction conditions were filtered out. Thirty-one studies met our inclusion criteria and were used in the qualitative synthesis. RESULTS: Studies are analyzed based on their results related to the effects of interaction type (e.g., audiovisual communication and/or physical interaction), interaction mode (collaborative, cooperative, co-active, and competitive), and partner characteristics. Visuo-physical interaction generally results in better dyadic task performance than visual interaction alone. In cases where the physical interaction between humans is described by a spring, there are conflicting results as to the effect of the stiffness of the spring. In terms of partner characteristics, having a more skilled partner improves dyadic task performance more than having a less skilled partner. However, conflicting results were observed in terms of individual motor learning. CONCLUSIONS: Although it is difficult to draw clear conclusions as to which interaction type, mode, or partner characteristic may lead to optimal task performance or individual motor learning, these results show the possibility for improved outcomes through HMH interaction. Future work that focuses on selecting the optimal personalized interaction conditions and exploring their impact on rehabilitation settings may facilitate the transition of HMH training protocols to clinical implementations.

Peripheral electrical stimulation to reduce pathological tremor: a review.

Interventions to reduce tremor in essential tremor (ET) and Parkinson's disease (PD) clinical populations often utilize pharmacological or surgical therapies. However, there can be significant side effects, decline in effectiveness over time, or clinical contraindications for these interventions. Therefore, alternative approaches must be considered and developed. Some non-pharmacological strategies include assistive devices, orthoses and mechanical loading of the tremorgenic limb, while others propose peripheral electrical stimulation. Specifically, peripheral electrical stimulation encompasses strategies that activate motor and sensory pathways to evoke muscle contractions and impact sensorimotor function. Numerous studies report the efficacy of peripheral electrical stimulation to alter tremor generation, thereby opening new perspectives for both short- and long-term tremor reduction. Therefore, it is timely to explore this promising modality in a comprehensive review. In this review, we analyzed 27 studies that reported the use of peripheral electrical stimulation to reduce tremor and discuss various considerations regarding peripheral electrical stimulation: the stimulation strategies and parameters, electrodes, experimental designs, results, and mechanisms hypothesized to reduce tremor. From our review, we identified a high degree of disparity across studies with regard to stimulation patterns, experimental designs and methods of assessing tremor. Having standardized experimental methodology is a critical step in the field and is needed in order to accurately compare results across studies. With this review, we explore peripheral electrical stimulation as an intervention for tremor reduction, identify the limitations and benefits of the current state-of-the-art studies, and provide ideas to guide the development of novel approaches based on the neural circuitries and mechanical properties implied in tremor generation.

Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease.

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).

Stroke in Patients With Peripheral Artery Disease.

Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients. Methods- EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Results- A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups. Conclusions- In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.

Voluntary and tremorogenic inputs to motor neuron pools of agonist/antagonist muscles in essential tremor patients.

Pathological tremor is an oscillation of body parts at 3-10 Hz, determined by the output of spinal motor neurons (MNs), which receive synaptic inputs from supraspinal centers and muscle afferents. The behavior of spinal MNs during tremor is not well understood, especially in relation to the activation of the multiple muscles involved. Recent studies on patients with essential tremor have shown that antagonist MN pools receive shared input at the tremor frequency. In this study, we investigated the synaptic inputs related to tremor and voluntary movement, and their coordination across antagonist muscles. We analyzed the spike trains of motor units (MUs) identified from high-density surface electromyography from the forearm extensor and flexor muscles in 15 patients with essential tremor during postural tremor. The shared synaptic input was quantified by coherence and phase difference analysis of the spike trains. All pairs of spike trains in each muscle showed coherence peaks at the voluntary drive frequency (1-3 Hz, 0.2 ± 0.2, mean ± SD) and tremor frequency (3-10 Hz, 0.6 ± 0.3) and were synchronized with small phase differences (3.3 ± 25.2° and 3.9 ± 22.0° for the voluntary drive and tremor frequencies, respectively). The coherence between MN spike trains of antagonist muscle groups at the tremor frequency was significantly smaller than intramuscular coherence. We predominantly observed in-phase activation of MUs between agonist/antagonist muscles at the voluntary frequency band (0.6 ± 48.8°) and out-of-phase activation at the tremor frequency band (126.9 ± 75.6°). Thus MNs innervating agonist/antagonist muscles concurrently receive synaptic inputs with different phase shifts in the voluntary and tremor frequency bands.NEW & NOTEWORTHY Although the mechanical characteristics of tremor have been widely studied, the activation of the affected muscles is still poorly understood. We analyzed the behavior of motor units of pairs of antagonistic wrist muscle groups in patients with essential tremor and studied their activity at voluntary movement- and tremor-related frequencies. We found that the phase relation between inputs to antagonistic muscles is different at the voluntary and tremor frequency bands.

Voluntary control of wearable robotic exoskeletons by patients with paresis via neuromechanical modeling.

BACKGROUND: Research efforts in neurorehabilitation technologies have been directed towards creating robotic exoskeletons to restore motor function in impaired individuals. However, despite advances in mechatronics and bioelectrical signal processing, current robotic exoskeletons have had only modest clinical impact. A major limitation is the inability to enable exoskeleton voluntary control in neurologically impaired individuals. This hinders the possibility of optimally inducing the activity-driven neuroplastic changes that are required for recovery. METHODS: We have developed a patient-specific computational model of the human musculoskeletal system controlled via neural surrogates, i.e., electromyography-derived neural activations to muscles. The electromyography-driven musculoskeletal model was synthesized into a human-machine interface (HMI) that enabled poststroke and incomplete spinal cord injury patients to voluntarily control multiple joints in a multifunctional robotic exoskeleton in real time. RESULTS: We demonstrated patients' control accuracy across a wide range of lower-extremity motor tasks. Remarkably, an increased level of exoskeleton assistance always resulted in a reduction in both amplitude and variability in muscle activations as well as in the mechanical moments required to perform a motor task. Since small discrepancies in onset time between human limb movement and that of the parallel exoskeleton would potentially increase human neuromuscular effort, these results demonstrate that the developed HMI precisely synchronizes the device actuation with residual voluntary muscle contraction capacity in neurologically impaired patients. CONCLUSIONS: Continuous voluntary control of robotic exoskeletons (i.e. event-free and task-independent) has never been demonstrated before in populations with paretic and spastic-like muscle activity, such as those investigated in this study. Our proposed methodology may open new avenues for harnessing residual neuromuscular function in neurologically impaired individuals via symbiotic wearable robots.

Compliant lower limb exoskeletons: a comprehensive review on mechanical design principles.

Exoskeleton technology has made significant advances during the last decade, resulting in a considerable variety of solutions for gait assistance and rehabilitation. The mechanical design of these devices is a crucial aspect that affects the efficiency and effectiveness of their interaction with the user. Recent developments have pointed towards compliant mechanisms and structures, due to their promising potential in terms of adaptability, safety, efficiency, and comfort. However, there still remain challenges to be solved before compliant lower limb exoskeletons can be deployed in real scenarios. In this review, we analysed 52 lower limb wearable exoskeletons, focusing on three main aspects of compliance: actuation, structure, and interface attachment components. We highlighted the drawbacks and advantages of the different solutions, and suggested a number of promising research lines. We also created and made available a set of data sheets that contain the technical characteristics of the reviewed devices, with the aim of providing researchers and end-users with an updated overview on the existing solutions.

Influences of the biofeedback content on robotic post-stroke gait rehabilitation: electromyographic vs joint torque biofeedback.

BACKGROUND: Add-on robot-mediated therapy has proven to be more effective than conventional therapy alone in post-stroke gait rehabilitation. Such robot-mediated interventions routinely use also visual biofeedback tools. A better understanding of biofeedback content effects when used for robotic locomotor training may improve the rehabilitation process and outcomes. METHODS: This randomized cross-over pilot trial aimed to address the possible impact of different biofeedback contents on patients' performance and experience during Lokomat training, by comparing a novel biofeedback based on online biological electromyographic information (EMGb) versus the commercial joint torque biofeedback (Rb) in sub-acute non ambulatory patients. 12 patients were randomized into two treatment groups, A and B, based on two different biofeedback training. For both groups, study protocol consisted of 12 Lokomat sessions, 6 for each biofeedback condition, 40 min each, 3 sessions per week of frequency. All patients performed Lokomat trainings as an add-on therapy to the conventional one that was the same for both groups and consisted of 40 min per day, 5 days per week. The primary outcome was the Modified Ashworth Spasticity Scale, and secondary outcomes included clinical, neurological, mechanical, and personal experience variables collected before and after each biofeedback training. RESULTS: Lokomat training significantly improved gait/daily living activity independence and trunk control, nevertheless, different effects due to biofeedback content were remarked. EMGb was more effective to reduce spasticity and improve muscle force at the ankle, knee and hip joints. Robot data suggest that Rb induces more adaptation to robotic movements than EMGb. Furthermore, Rb was perceived less demanding than EMGb, even though patient motivation was higher for EMGb. Robot was perceived to be effective, easy to use, reliable and safe: acceptability was rated as very high by all patients. CONCLUSIONS: Specific effects can be related to biofeedback content: when muscular-based information is used, a more direct effect on lower limb spasticity and muscle activity is evidenced. In a similar manner, when biofeedback treatment is based on joint torque data, a higher patient compliance effect in terms of force exerted is achieved. Subjects who underwent EMGb seemed to be more motivated than those treated with Rb.

Volition-adaptive control for gait training using wearable exoskeleton: preliminary tests with incomplete spinal cord injury individuals.

BACKGROUND: Gait training for individuals with neurological disorders is challenging in providing the suitable assistance and more adaptive behaviour towards user needs. The user specific adaptation can be defined based on the user interaction with the orthosis and by monitoring the user intentions. In this paper, an adaptive control model, commanded by the user intention, is evaluated using a lower limb exoskeleton with incomplete spinal cord injury individuals (SCI). METHODS: A user intention based adaptive control model has been developed and evaluated with 4 incomplete SCI individuals across 3 sessions of training per individual. The adaptive control model modifies the joint impedance properties of the exoskeleton as a function of the human-orthosis interaction torques and the joint trajectory evolution along the gait sequence, in real time. The volitional input of the user is identified by monitoring the neural signals, pertaining to the user's motor activity. These volitional inputs are used as a trigger to initiate the gait movement, allowing the user to control the initialization of the exoskeleton movement, independently. A Finite-state machine based control model is used in this set-up which helps in combining the volitional orders with the gait adaptation. RESULTS: The exoskeleton demonstrated an adaptive assistance depending on the patients' performance without guiding them to follow an imposed trajectory. The exoskeleton initiated the trajectory based on the user intention command received from the brain machine interface, demonstrating it as a reliable trigger. The exoskeleton maintained the equilibrium by providing suitable assistance throughout the experiments. A progressive change in the maximum flexion of the knee joint was observed at the end of each session which shows improvement in the patient performance. Results of the adaptive impedance were evaluated by comparing with the application of a constant impedance value. Participants reported that the movement of the exoskeleton was flexible and the walking patterns were similar to their own distinct patterns. CONCLUSIONS: This study demonstrates that user specific adaptive control can be applied on a wearable robot based on the human-orthosis interaction torques and modifying the joints' impedance properties. The patients perceived no external or impulsive force and felt comfortable with the assistance provided by the exoskeleton. The main goal of such a user dependent control is to assist the patients' needs and adapt to their characteristics, thus maximizing their engagement in the therapy and avoiding slacking. In addition, the initiation directly controlled by the brain allows synchronizing the user's intention with the afferent stimulus provided by the movement of the exoskeleton, which maximizes the potentiality of the system in neuro-rehabilitative therapies.

Global Kalman filter approaches to estimate absolute angles of lower limb segments.

BACKGROUND: In this paper we propose the use of global Kalman filters (KFs) to estimate absolute angles of lower limb segments. Standard approaches adopt KFs to improve the performance of inertial sensors based on individual link configurations. In consequence, for a multi-body system like a lower limb exoskeleton, the inertial measurements of one link (e.g., the shank) are not taken into account in other link angle estimations (e.g., foot). Global KF approaches, on the other hand, correlate the collective contribution of all signals from lower limb segments observed in the state-space model through the filtering process. We present a novel global KF (matricial global KF) relying only on inertial sensor data, and validate both this KF and a previously presented global KF (Markov Jump Linear Systems, MJLS-based KF), which fuses data from inertial sensors and encoders from an exoskeleton. We furthermore compare both methods to the commonly used local KF. RESULTS: The results indicate that the global KFs performed significantly better than the local KF, with an average root mean square error (RMSE) of respectively 0.942° for the MJLS-based KF, 1.167° for the matrical global KF, and 1.202° for the local KFs. Including the data from the exoskeleton encoders also resulted in a significant increase in performance. CONCLUSION: The results indicate that the current practice of using KFs based on local models is suboptimal. Both the presented KF based on inertial sensor data, as well our previously presented global approach fusing inertial sensor data with data from exoskeleton encoders, were superior to local KFs. We therefore recommend to use global KFs for gait analysis and exoskeleton control.

The phase difference between neural drives to antagonist muscles in essential tremor is associated with the relative strength of supraspinal and afferent input.

The pathophysiology of essential tremor (ET), the most common movement disorder, is not fully understood. We investigated which factors determine the variability in the phase difference between neural drives to antagonist muscles, a long-standing observation yet unexplained. We used a computational model to simulate the effects of different levels of voluntary and tremulous synaptic input to antagonistic motoneuron pools on the tremor. We compared these simulations to data from 11 human ET patients. In both analyses, the neural drive to muscle was represented as the pooled spike trains of several motor units, which provides an accurate representation of the common synaptic input to motoneurons. The simulations showed that, for each voluntary input level, the phase difference between neural drives to antagonist muscles is determined by the relative strength of the supraspinal tremor input to the motoneuron pools. In addition, when the supraspinal tremor input to one muscle was weak or absent, Ia afferents provided significant common tremor input due to passive stretch. The simulations predicted that without a voluntary drive (rest tremor) the neural drives would be more likely in phase, while a concurrent voluntary input (postural tremor) would lead more frequently to an out-of-phase pattern. The experimental results matched these predictions, showing a significant change in phase difference between postural and rest tremor. They also indicated that the common tremor input is always shared by the antagonistic motoneuron pools, in agreement with the simulations. Our results highlight that the interplay between supraspinal input and spinal afferents is relevant for tremor generation.

Advances in selective activation of muscles for non-invasive motor neuroprostheses.

Non-invasive neuroprosthetic (NP) technologies for movement compensation and rehabilitation remain with challenges for their clinical application. Two of those major challenges are selective activation of muscles and fatigue management. This review discusses how electrode arrays improve the efficiency and selectivity of functional electrical stimulation (FES) applied via transcutaneous electrodes. In this paper we review the principles and achievements during the last decade on techniques for artificial motor unit recruitment to improve the selective activation of muscles. We review the key factors affecting the outcome of muscle force production via multi-pad transcutaneous electrical stimulation and discuss how stimulation parameters can be set to optimize external activation of body segments. A detailed review of existing electrode array systems proposed by different research teams is also provided. Furthermore, a review of the targeted applications of existing electrode arrays for control of upper and lower limb NPs is provided. Eventually, last section demonstrates the potential of electrode arrays to overcome the major challenges of NPs for compensation and rehabilitation of patient-specific impairments.