Quality of Life: The Interplay between Human Behaviour, Technology and the Environment.

Quality of life is an umbrella term for the quality of the various domains in life [...].

Early Shortening of Wrist Flexor Muscles Coincides With Poor Recovery After Stroke.

BACKGROUND: The mechanism and time course of increased wrist joint stiffness poststroke and clinically observed wrist flexion deformity is still not well understood. The components contributing to increased joint stiffness are of neural reflexive and peripheral tissue origin and quantified by reflexive torque and muscle slack length and stiffness coefficient parameters. OBJECTIVE: To investigate the time course of the components contributing to wrist joint stiffness during the first 26 weeks poststroke in a group of patients, stratified by prognosis and functional recovery of the upper extremity. METHODS: A total of 36 stroke patients were measured on 8 occasions within the first 26 weeks poststroke using ramp-and-hold rotations applied to the wrist joint by a robot manipulator. Neural reflexive and peripheral tissue components were estimated using an electromyography-driven antagonistic wrist model. Outcome was compared between groups cross-sectionally at 26 weeks poststroke and development over time was analyzed longitudinally. RESULTS: At 26 weeks poststroke, patients with poor recovery (Action Research Arm Test [ARAT] ≤9 points) showed a higher predicted reflexive torque of the flexors ( P < .001) and reduced predicted slack length ( P < .001) indicating shortened muscles contributing to higher peripheral tissue stiffness ( P < .001), compared with patients with good recovery (ARAT ≥10 points). Significant differences in peripheral tissue stiffness between groups could be identified around weeks 4 and 5; for neural reflexive stiffness, this was the case around week 12. CONCLUSIONS: We found onset of peripheral tissue stiffness to precede neural reflexive stiffness. Temporal identification of components contributing to joint stiffness after stroke may prompt longitudinal interventional studies to further evaluate and eventually prevent these phenomena.

Perturbation velocity affects linearly estimated neuromechanical wrist joint properties.

The dynamic behavior of the wrist joint is governed by nonlinear properties, yet applied mathematical models, used to describe the measured input-output (perturbation-response) relationship, are commonly linear. Consequently, the linearly estimated model parameters will depend on properties of the applied perturbation properties (such perturbation amplitude and velocity). We aimed to systematically address the effects of perturbation velocity on linearly estimated neuromechanical parameters. Using a single axis manipulator ramp and hold perturbations were applied to the wrist joint. Effects of perturbation velocity (0.5, 1 and 3 rad/s) were investigated at multiple background torque levels (0, 0.5 and 1 N·m). With increasing perturbation velocity, estimated joint stiffness remained constant, while damping and reflex gain decreased. This variation in model parameters is dependent on background torque levels, i.e. muscle contraction. These observations support the future development of nonlinear models that are capable of describing wrist joint behavior over a larger range of loading conditions, exceeding the restricted range of operation that is required for linearization.

Cocontraction measured with short-range stiffness was higher in obstetric brachial plexus lesions patients compared to healthy subjects.

We suggest short range stiffness (SRS) at the elbow joint as an alternative diagnostic for EMG to assess cocontraction. Elbow SRS is compared between obstetric brachial plexus lesion (OBPL) patients and healthy subjects (cross-sectional study design). Seven controls (median 28years) and five patients (median 31years) isometrically flexed and extended the elbow at rest and three additional torques [2.1,4.3,6.4Nm] while a fast stretch stimulus was applied. SRS was estimated in silico using a neuromechanical elbow model simulating the torque response from the imposed elbow angle. SRS was higher in patients (250±36Nm/rad) than in controls (150±21Nm/rad, p=0.014), except for the rest condition. Higher elbow SRS suggested greater cocontraction in patients compared to controls. SRS is a promising mechanical alternative to assess cocontraction, which is a frequently encountered clinical problem in OBPL due to axonal misrouting.

Manipulation of visual information affects control strategy during a visuomotor tracking task.

Proper understanding of motor control requires insight into the extent and manner in which task performance and control strategy are influenced by various aspects of visual information. We therefore systematically manipulated the visual presentation (i.e., scaling factor and optical flow density) of a visuomotor tracking task without changing the task itself, and investigated the effect on performance, effort, motor control strategy (i.e., anticipatory or corrective steering) and underlying neuromechanical parameters (i.e., intrinsic muscle stiffness and damping, and proprioceptive and visual feedback). Twenty healthy participants controlled the left-right position of a virtual car (by means of wrist rotations in a haptic robot) to track a slightly curved virtual road (presented on a 60" LED screen), while small torque perturbations were applied to the wrist (1.25-20Hz multisine) for quantification of the neuromechanical parameters. This visuomotor tracking task was performed in conditions with low/medium/high scaling factor and low/high optical flow density. Task performance was high in all conditions (tracking accuracy 96.6%-100%); a higher scaling factor was associated with slightly better performance. As expected, participants did adapt their control strategy and the use of proprioceptive and visual feedback in response to changes in the visual presentation. These findings indicate that effects of visual representation on motor behavior should be taken into consideration in designing, interpreting and comparing experiments on motor control in health and disease. In future studies, these insights might be exploited to assess the sensory-motor adaptability in various clinical conditions.

Estimation of tissue stiffness, reflex activity, optimal muscle length and slack length in stroke patients using an electromyography driven antagonistic wrist model.

BACKGROUND: About half of all chronic stroke patients experience loss of arm function coinciding with increased stiffness, reduced range of motion and a flexed wrist due to a change in neural and/or structural tissue properties. Quantitative assessment of these changes is of clinical importance, yet not trivial. The goal of this study was to quantify the neural and structural properties contributing to wrist joint stiffness and to compare these properties between healthy subjects and stroke patients. METHODS: Stroke patients (n=32) and healthy volunteers (n=14) were measured using ramp-and-hold rotations applied to the wrist joint by a haptic manipulator. Neural (reflexive torque) and structural (connective tissue stiffness and slack lengths and (contractile) optimal muscle lengths) parameters were estimated using an electromyography driven antagonistic wrist model. Kruskal-Wallis analysis with multiple comparisons was used to compare results between healthy subjects, stroke patients with modified Ashworth score of zero and stroke patients with modified Ashworth score of one or more. FINDINGS: Stroke patients with modified Ashworth score of one or more differed from healthy controls (P<0.05) by increased tissue stiffness, increased reflexive torque, decreased optimal muscle length and decreased slack length of connective tissue of the flexor muscles. INTERPRETATION: Non-invasive quantitative analysis, including estimation of optimal muscle lengths, enables to identify neural and non-neural changes in chronic stroke patients. Monitoring these changes in time is important to understand the recovery process and to optimize treatment.

Effects of Unilateral Upper Limb Training in Two Distinct Prognostic Groups Early After Stroke: The EXPLICIT-Stroke Randomized Clinical Trial.

Background and Objective Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered neuromuscular stimulation (EMG-NMS) on upper limb capacity early poststroke. Methods A total of 159 ischemic stroke patients were included: 58 patients with a favorable prognosis (>10° of FE) were randomly allocated to 3 weeks of mCIMT or usual care only; 101 patients with an unfavorable prognosis were allocated to 3-week EMG-NMS or usual care only. Both interventions started within 14 days poststroke, lasted up until 5 weeks, focused at preservation or return of FE. Results Upper limb capacity was measured with the Action Research Arm Test (ARAT), assessed weekly within the first 5 weeks poststroke and at postassessments at 8, 12, and 26 weeks. Clinically relevant differences in ARAT in favor of mCIMT were found after 5, 8, and 12 weeks poststroke (respectively, 6, 7, and 7 points; P < .05), but not after 26 weeks. We did not find statistically significant differences between mCIMT and usual care on impairment measures, such as the Fugl-Meyer assessment of the arm (FMA-UE). EMG-NMS did not result in significant differences. Conclusions Three weeks of early mCIMT is superior to usual care in terms of regaining upper limb capacity in patients with a favorable prognosis; 3 weeks of EMG-NMS in patients with an unfavorable prognosis is not beneficial. Despite meaningful improvements in upper limb capacity, no evidence was found that the time-dependent neurological improvements early poststroke are significantly influenced by either mCIMT or EMG-NMS.

NeuroControl of movement: system identification approach for clinical benefit.

Progress in diagnosis and treatment of movement disorders after neurological diseases like stroke, cerebral palsy (CP), dystonia and at old age requires understanding of the altered capacity to adequately respond to physical obstacles in the environment. With posture and movement disorders, the control of muscles is hampered, resulting in aberrant force generation and improper impedance regulation. Understanding of this improper regulation not only requires the understanding of the role of the neural controller, but also attention for: (1) the interaction between the neural controller and the "plant", comprising the biomechanical properties of the musculaskeletal system including the viscoelastic properties of the contractile (muscle) and non-contractile (connective) tissues: neuromechanics; and (2) the closed loop nature of neural controller and biomechanical system in which cause and effect interact and are hence difficult to separate. Properties of the neural controller and the biomechanical system need to be addressed synchronously by the combination of haptic robotics, (closed loop) system identification (SI), and neuro-mechanical modeling. In this paper, we argue that assessment of neuromechanics in response to well defined environmental conditions and tasks may provide for key parameters to understand posture and movement disorders in neurological diseases and for biomarkers to increase accuracy of prediction models for functional outcome and effects of intervention.

The validity and reliability of modelled neural and tissue properties of the ankle muscles in children with cerebral palsy.

Spastic cerebral palsy (CP) is characterized by increased joint resistance, caused by a mix of increased tissue stiffness, as well as involuntary reflex and background muscle activity. These properties can be quantified using a neuromechanical model of the musculoskeletal complex and instrumented assessment. The construct validity of the neuromechanical parameters was examined (i.e. the internal model validity, effect of knee angle, speed and age, sensitivity to patients versus controls, spasticity severity and treatment), together with the repeatability. We included 38 children with CP and 35 controls. A motor driven footplate applied two slow (15°/s) and two fast (100°/s) rotations around the ankle joint, at two different knee angles. Ankle angle, torque and EMG of the gastrocnemius (GA), soleus (SO) and tibialis anterior (TA) muscle were used to optimize a nonlinear neuromuscular model. Outcome measures were tissue stiffness, reflex and background activity for GA, SO and TA. The internal model validity showed medium to high parameter confidence and good model fits. All parameter could discriminate between patients with CP and controls according to CP pathology. Other measures of external model validity (effect of test position, speed and age) showed behaviour along the lines of current knowledge of physiology. GA/SO background activity was sensitive to spasticity severity, but reflex activity was not. Preliminary data indicated that reflex activity was reduced after spasticity treatment. The between-trial and -day repeatability was moderate to good. The large variance between patients in the ratio of stiffness and neural resistance indicates that the method could potentially contribute to patient-specific treatment selection.

Comprehensive neuromechanical assessment in stroke patients: reliability and responsiveness of a protocol to measure neural and non-neural wrist properties.

BACKGROUND: Understanding movement disorder after stroke and providing targeted treatment for post stroke patients requires valid and reliable identification of biomechanical (passive) and neural (active and reflexive) contributors. Aim of this study was to assess test-retest reliability of passive, active and reflexive parameters and to determine clinical responsiveness in a cohort of stroke patients with upper extremity impairments and healthy volunteers. METHODS: Thirty-two community-residing chronic stroke patients with an impairment of an upper limb and fourteen healthy volunteers were assessed with a comprehensive neuromechanical assessment protocol consisting of active and passive tasks and different stretch reflex-eliciting measuring velocities, using a haptic manipulator and surface electromyography of wrist flexor and extensor muscles (Netherlands Trial Registry number NTR1424). Intraclass correlation coefficients (ICC) and Standard Error of Measurement were calculated to establish relative and absolute test-retest reliability of passive, active and reflexive parameters. Clinical responsiveness was tested with Kruskal Wallis test for differences between groups. RESULTS: ICC of passive parameters were fair to excellent (0.45 to 0.91). ICC of active parameters were excellent (0.88-0.99). ICC of reflexive parameters were fair to good (0.50-0.74). Only the reflexive loop time of the extensor muscles performed poor (ICC 0.18). Significant differences between chronic stroke patients and healthy volunteers were found in ten out of fourteen parameters. CONCLUSIONS: Passive, active and reflexive parameters can be assessed with high reliability in post-stroke patients. Parameters were responsive to clinical status. The next step is longitudinal measurement of passive, active and reflexive parameters to establish their predictive value for functional outcome after stroke.

Nonlinear 2D arm dynamics in response to continuous and pulse-shaped force perturbations.

Ample evidence exists regarding the nonlinearity of the neuromuscular system but linear models are widely applied to capture postural dynamics. This study quantifies the nonlinearity of human arm postural dynamics applying 2D continuous force perturbations (0.2-40 Hz) inducing three levels of hand displacement (5, 15, 45 mm RMS) followed by force-pulse perturbations inducing large hand displacements (up to 250 mm) in a position task (PT) and a relax task (RT) recording activity of eight shoulder and elbow muscles. The continuous perturbation data were used to analyze the 2D endpoint dynamics in the frequency domain and to identify reflexive and intrinsic parameters of a linear neuromuscular shoulder-elbow model. Subsequently, it was assessed to what extent the large displacements in response to force pulses could be predicted from the 'small amplitude' linear neuromuscular model. Continuous and pulse perturbation responses with varying amplitudes disclosed highly nonlinear effects. In PT, a larger continuous perturbation induced stiffening with a factor of 1.5 attributed to task adaptation evidenced by increased co-contraction and reflexive activity. This task adaptation was even more profound in the pulse responses where reflexes and displacements were strongly affected by the presence and amplitude of preceding continuous perturbations. In RT, a larger continuous perturbation resulted in yielding with a factor of 3.8 attributed to nonlinear mechanical properties as no significant reflexive activity was found. Pulse perturbations always resulted in yielding where a model fitted to the preceding 5-mm continuous perturbations predicted only 37% of the recorded peak displacements in RT and 79% in PT. This demonstrates that linear neuromuscular models, identified using continuous perturbations with small amplitudes, strongly underestimate displacements in pulse-shaped (e.g., impact) loading conditions. The data will be used to validate neuromuscular models including nonlinear muscular (e.g., Hill and Huxley) and reflexive components.

Perturbation amplitude affects linearly estimated neuromechanical wrist joint properties.

System identification techniques have been used to separate intrinsic muscular and reflexive contributions to joint impedance, which is an essential step in the proper choice of patient specific treatment. These techniques are, however, only well developed for linear systems. Assuming linearity prescribes the neuromuscular system to be perturbed only around predefined operating points. In this study, we test the validity of a commonly used linear model by analyzing the effects of flexion-extension displacement amplitude (2(°), 4(°), and 8(°)) on damping, stiffness, and reflex gain of the wrist joint, at different background torque levels (0, 1, and 2 N · m). With displacement amplitude, intrinsic damping increased, while intrinsic stiffness and reflex gains decreased. These changes were dependent on the level of wrist torque. The dependency of the neuromuscular system properties on even small variations in angular displacement is evident and has to be accounted for when comparing different studies and clinical interpretations using linear identification techniques. Knowledge of the behavior of the neuromuscular system around operating points is an essential step toward the development of nonlinear models that allow for discrimination between patients and controls in a larger range of loading conditions.

Differentiation between non-neural and neural contributors to ankle joint stiffness in cerebral palsy.

BACKGROUND: Spastic paresis in cerebral palsy (CP) is characterized by increased joint stiffness that may be of neural origin, i.e. improper muscle activation caused by e.g. hyperreflexia or non-neural origin, i.e. altered tissue viscoelastic properties (clinically: "spasticity" vs. "contracture"). Differentiation between these components is hard to achieve by common manual tests. We applied an assessment instrument to obtain quantitative measures of neural and non-neural contributions to ankle joint stiffness in CP. METHODS: Twenty-three adolescents with CP and eleven healthy subjects were seated with their foot fixated to an electrically powered single axis footplate. Passive ramp-and-hold rotations were applied over full ankle range of motion (RoM) at low and high velocities. Subject specific tissue stiffness, viscosity and reflexive torque were estimated from ankle angle, torque and triceps surae EMG activity using a neuromuscular model. RESULTS: In CP, triceps surae reflexive torque was on average 5.7 times larger (p = .002) and tissue stiffness 2.1 times larger (p = .018) compared to controls. High tissue stiffness was associated with reduced RoM (p < .001). Ratio between neural and non-neural contributors varied substantially within adolescents with CP. Significant associations of SPAT (spasticity test) score with both tissue stiffness and reflexive torque show agreement with clinical phenotype. CONCLUSIONS: Using an instrumented and model based approach, increased joint stiffness in CP could be mainly attributed to higher reflexive torque compared to control subjects. Ratios between contributors varied substantially within adolescents with CP. Quantitative differentiation of neural and non-neural stiffness contributors in CP allows for assessment of individual patient characteristics and tailoring of therapy.

Reduction of the linear reflex gain explained from the M1-M2 refractory period.

Linear system identification methods combined with neuromechanical modeling enable the quantification of reflex gains from recorded joint angular perturbation, torque, and/or electromyography (EMG). However, the stretch reflex response as recorded by EMG consists of multiple consecutive activation volleys (M1 and M2 responses) separated by a period of reduced activity and is nonlinearly related to joint perturbation. The goal of this study is to assess to what extent linear assumptions hold when quantifying these reflexive responses. Series of ramp-and-hold angular perturbations with fixed velocity but different ramp durations (and, therefore, different amplitudes) were applied to the wrist joint of seven healthy volunteers. Evoked EMG responses were compared to the reflex response estimated from a common linear reflex model relating EMG to perturbation velocity. Model fits described the measured EMG responses best when the perturbation and M1 response durations were equivalent. With increasing perturbation duration, i.e., amplitude, EMG response increased but reflex gain decreased due to the inert period after M1, which is believed to be related to alignment of the refractory period of the motoneurons. For angular joint perturbations exceeding the M1 duration (coinciding with 2 (°) of wrist joint rotation in this study), reflex gain variation may be largely explained from a shortcoming of the linear model in describing the nonlinear reflex response, and in particular the period of low reflexive activity after M1.

Clonus is explained from increased reflex gain and enlarged tissue viscoelasticity.

Upper motor neuron diseases (UMND), such as stroke and spinal cord injury (SCI), are assumed to produce alterations in muscle tissue in association with neural damage. Distinguishing between these two factors is of clinical importance in choosing appropriate therapy. We studied the effect of changes in the gain of the Ia reflex pathway and tissue viscoelasticity on the emergence, frequency, and persistence of ankle clonus: a clinically significant, involuntary oscillatory movement disorder. Monte Carlo simulations were performed to explain our experimental observations in patients with stroke (n = 3) and SCI (n = 4) using a nonlinear antagonistic muscle model of the human ankle joint. Ia reflex gain was varied by changing motor unit pool threshold and gain, and passive tissue viscosity and elasticity were varied by changing optimal muscle length. Tissue viscoelasticity appeared to have a strong effect on the emergence and persistence of clonus. Observed frequencies of ankle movement, prior to and after the experimental intervention of a sudden damper, was predicted by the model. The simulations revealed that reflex gains were largest in patients with the largest tissue viscoelasticity. We conclude that ankle clonus in stroke and SCI is the result of a combination of, and suggests a relation between, (i) a decrease in threshold and an increase in gain of the motor unit pool and (ii) a decrease in optimal muscle length.

Parameter estimation of the Huxley cross-bridge muscle model in humans.

The Huxley model has the potential to provide more accurate muscle dynamics while affording a physiological interpretation at cross-bridge level. By perturbing the wrist at different velocities and initial force levels, reliable Huxley model parameters were estimated in humans in vivo using a Huxley muscle-tendon complex. We conclude that these estimates may be used to investigate and monitor changes in microscopic elements of muscle functioning from experiments at joint level.

Short range stiffness elastic limit depends on joint velocity.

Muscles behave as elastic springs during the initial strain phase, indicated as short range stiffness (SRS). Beyond a certain amount of strain the muscle demonstrates a more viscous behavior. The strain at which the muscle transits from elastic- to viscous-like behavior is called the elastic limit and is believed to be the result of breakage of cross-bridges between the contractile filaments. The aim of this study was to test whether the elastic limit, measured in vivo at the wrist joint, depended on the speed of lengthening. Brief extension rotations were imposed to the wrist joint (n=8) at four different speeds and at three different levels of voluntary torque using a servo controlled electrical motor. Using a recently published identification scheme, we quantified the elastic limit from measured joint angle and torque. The results showed that the elastic limit significantly increased with speed in a linear way, indicating to a constant time of approximately 30 ms before cross-bridges break. The implications for movement control of the joint are discussed.

The relation between neuromechanical parameters and Ashworth score in stroke patients.

BACKGROUND: Quantifying increased joint resistance into its contributing factors i.e. stiffness and viscosity ("hypertonia") and stretch reflexes ("hyperreflexia") is important in stroke rehabilitation. Existing clinical tests, such as the Ashworth Score, do not permit discrimination between underlying tissue and reflexive (neural) properties. We propose an instrumented identification paradigm for early and tailor made interventions. METHODS: Ramp-and-Hold ankle dorsiflexion rotations of various durations were imposed using a manipulator. A one second rotation over the Range of Motion similar to the Ashworth condition was included. Tissue stiffness and viscosity and reflexive torque were estimated using a nonlinear model and compared to the Ashworth Score of nineteen stroke patients and seven controls. RESULTS: Ankle viscosity moderately increased, stiffness was indifferent and reflexive torque decreased with movement duration. Compared to controls, patients with an Ashworth Score of 1 and 2+ were significantly stiffer and had higher viscosity and patients with an Ashworth Score of 2+ showed higher reflexive torque. For the one second movement, stiffness correlated to Ashworth Score (r2 = 0.51, F = 32.7, p < 0.001) with minor uncorrelated reflexive torque. Reflexive torque correlated to Ashworth Score at shorter movement durations (r2 = 0.25, F = 11, p = 0.002). CONCLUSION: Stroke patients were distinguished from controls by tissue stiffness and viscosity and to a lesser extent by reflexive torque from the soleus muscle. These parameters were also sensitive to discriminate patients, clinically graded by the Ashworth Score. Movement duration affected viscosity and reflexive torque which are clinically relevant parameters. Full evaluation of pathological joint resistance therefore requires instrumented tests at various movement conditions.

In vivo estimation of the short-range stiffness of cross-bridges from joint rotation.

Short-range stiffness (SRS) is a mechanical property of muscles that is characterized by a disproportionally high stiffness within a short length range during both lengthening and shortening movements. SRS is attributed to the cross-bridges and is beneficial for stabilizing a joint during, e.g., postural conditions. Thus far, SRS has been estimated mainly on isolated mammalian muscles. In this study we presented a method to estimate SRS in vivo in the human wrist joint. SRS was estimated at joint level in the angular domain (Nm/rad) for both flexion and extension rotations of the human wrist in nine healthy subjects. Wrist rotations of 0.15rad at 3rad/s were imposed at eight levels of voluntary contraction ranging from 0 to 2.1Nm by means of a single axis manipulator. Flexion and extension SRS of the wrist joint was estimated consistently and accurately using a dynamic nonlinear model that was fitted onto the recorded wrist torque. SRS increased monotonically with torque in a way consistent with previous studies on isolated muscles. It is concluded that in vivo measurement of joint SRS represents the population of coupled cross-bridges in wrist flexor and extensor muscles. In its current form, the presented technique can be used for clinical applications in many neurological and muscular diseases where altered joint torque and (dissociated) joint stiffness are important clinical parameters.

Muscle weakness and lack of reflex gain adaptation predominate during post-stroke posture control of the wrist.

BACKGROUND: Instead of hyper-reflexia as sole paradigm, post-stroke movement disorders are currently considered the result of a complex interplay between neuronal and muscular properties, modified by level of activity. We used a closed loop system identification technique to quantify individual contributors to wrist joint stiffness during an active posture task. METHODS: Continuous random torque perturbations applied to the wrist joint by a haptic manipulator had to be resisted maximally. Reflex provoking conditions were applied i.e. additional viscous loads and reduced perturbation signal bandwidth. Linear system identification and neuromuscular modeling were used to separate joint stiffness into the intrinsic resistance of the muscles including co-contraction and the reflex mediated contribution. RESULTS: Compared to an age and sex matched control group, patients showed an overall 50% drop in intrinsic elasticity while their reflexive contribution did not respond to provoking conditions. Patients showed an increased mechanical stability compared to control subjects. CONCLUSION: Post stroke, we found active posture tasking to be dominated by: 1) muscle weakness and 2) lack of reflex adaptation. This adds to existing doubts on reflex blocking therapy as the sole paradigm to improve active task performance and draws attention to muscle strength and power recovery and the role of the inability to modulate reflexes in post stroke movement disorders.