Examining the role of intrinsic and reflexive contributions to ankle joint hyper-resistance treated with botulinum toxin-A.

BACKGROUND: Spasticity, i.e. stretch hyperreflexia, increases joint resistance similar to symptoms like hypertonia and contractures. Botulinum neurotoxin-A (BoNT-A) injections are a widely used intervention to reduce spasticity. BoNT-A effects on spasticity are poorly understood, because clinical measures, e.g. modified Ashworth scale (MAS), cannot differentiate between the symptoms affecting joint resistance. This paper distinguishes the contributions of the reflexive and intrinsic pathways to ankle joint hyper-resistance for participants treated with BoNT-A injections. We hypothesized that the overall joint resistance and reflexive contribution decrease 6 weeks after injection, while returning close to baseline after 12 weeks. METHODS: Nine participants with spasticity after spinal cord injury or after stroke were evaluated across three sessions: 0, 6 and 12 weeks after BoNT-A injection in the calf muscles. Evaluation included clinical measures (MAS, Tardieu Scale) and motorized instrumented assessment using the instrumented spasticity test (SPAT) and parallel-cascade (PC) system identification. Assessments included measures for: (1) overall resistance from MAS and fast velocity SPAT; (2) reflexive resistance contribution from Tardieu Scale, difference between fast and slow velocity SPAT and PC reflexive gain; and (3) intrinsic resistance contribution from slow velocity SPAT and PC intrinsic stiffness/damping. RESULTS: Individually, the hypothesized BoNT-A effect, the combination of a reduced resistance (week 6) and return towards baseline (week 12), was observed in the MAS (5 participants), fast velocity SPAT (2 participants), Tardieu Scale (2 participants), SPAT (1 participant) and reflexive gain (4 participants). On group-level, the hypothesis was only confirmed for the MAS, which showed a significant resistance reduction at week 6. All instrumented measures were strongly correlated when quantifying the same resistance contribution. CONCLUSION: At group-level, the expected joint resistance reduction due to BoNT-A injections was only observed in the MAS (overall resistance). This observed reduction could not be attributed to an unambiguous group-level reduction of the reflexive resistance contribution, as no instrumented measure confirmed the hypothesis. Validity of the instrumented measures was supported through a strong association between different assessment methods. Therefore, further quantification of the individual contributions to joint resistance changes using instrumented measures across a large sample size are essential to understand the heterogeneous response to BoNT-A injections.

Disentangling acceleration-, velocity-, and duration-dependency of the short- and medium-latency stretch reflexes in the ankle plantarflexors.

Motorized assessment of the stretch reflex is instrumental to gain understanding of the stretch reflex, its physiological origin and to differentiate effects of neurological disorders, like spasticity. Both short-latency (M1) and medium-latency (M2) stretch reflexes have been reported to depend on the velocity and acceleration of an applied ramp-and-hold perturbation. In the upper limb, M2 has also been reported to depend on stretch duration. However, wrong conclusions might have been drawn in previous studies as the interdependence of perturbation parameters (amplitude, duration, velocity, and acceleration) possibly created uncontrolled, confounding effects. We disentangled the duration-, velocity-, and acceleration-dependence and their interactions of the M1 and M2 stretch reflex in the ankle plantarflexors. To disentangle the parameter interdependence, 49 unique ramp-and-hold joint perturbations elicited reflexes in 10 healthy volunteers during a torque control task. Linear mixed model analysis showed that M1 depended on acceleration, not velocity or duration, whereas M2 depended on acceleration, velocity, and duration. Simulations of the muscle spindle Ia afferents coupled to a motoneuron pool corroborated these experimental findings. In addition, this simulation model did show a nonlinear M1 velocity- and duration-dependence for perturbation parameters outside the experimental scope. In conclusion, motorized assessment of the stretch reflex or spasticity using ramp-and-hold perturbations should be systematically executed and reported. Our systematic motorized and simulation assessments showed that M1 and M2 depend on acceleration, velocity, and duration of the applied perturbation. The simulation model suggested that these dependencies emerge from: muscle-tendon unit and muscle cross-bridge dynamics, Ia sensitivity to force and yank, and motoneuron synchronization.NEW & NOTEWORTHY Previous research and definitions of the stretch reflex and spasticity have focused on velocity-dependence. We showed that perturbation acceleration, velocity, and duration all shape the M1 and M2 response, often via nonlinear or interacting dependencies. Consequently, systematic execution and reporting of stretch reflex and spasticity studies, avoiding uncontrolled parameter interdependence, is essential for proper understanding of the reflex neurophysiology.

Neurophysiological validation of simultaneous intrinsic and reflexive joint impedance estimates.

BACKGROUND: People with brain or neural injuries, such as cerebral palsy or spinal cord injury, commonly have joint hyper-resistance. Diagnosis and treatment of joint hyper-resistance is challenging due to a mix of tonic and phasic contributions. The parallel-cascade (PC) system identification technique offers a potential solution to disentangle the intrinsic (tonic) and reflexive (phasic) contributions to joint impedance, i.e. resistance. However, a simultaneous neurophysiological validation of both intrinsic and reflexive joint impedances is lacking. This simultaneous validation is important given the mix of tonic and phasic contributions to joint hyper-resistance. Therefore, the main goal of this paper is to perform a group-level neurophysiological validation of the PC system identification technique using electromyography (EMG) measurements. METHODS: Ten healthy people participated in the study. Perturbations were applied to the ankle joint to elicit reflexes and allow for system identification. Participants completed 20 hold periods of 60 seconds, assumed to have constant joint impedance, with varying magnitudes of intrinsic and reflexive joint impedances across periods. Each hold period provided a paired data point between the PC-based estimates and neurophysiological measures, i.e. between intrinsic stiffness and background EMG, and between reflexive gain and reflex EMG. RESULTS: The intrinsic paired data points, with all subjects combined, were strongly correlated, with a range of [Formula: see text] in both ankle plantarflexors and dorsiflexors. The reflexive paired data points were moderately correlated, with [Formula: see text] in the ankle plantarflexors only. CONCLUSION: An agreement with the neurophysiological basis on which PC algorithms are built is necessary to support its clinical application in people with joint hyper-resistance. Our results show this agreement for the PC system identification technique on group-level. Consequently, these results show the validity of the use of the technique for the integrated assessment and training of people with joint hyper-resistance in clinical practice.

Reducing the Soleus Stretch Reflex With Conditioning: Exploring Game- and Impedance-Based Biofeedback.

People with spasticity, i.e., stretch hyperreflexia, have a limited functional independence and mobility. While a broad range of spasticity treatments is available, many treatments are invasive, non-specific, or temporary and might have negative side effects. Operant conditioning of the stretch reflex is a promising non-invasive paradigm with potential long-term sustained effects. Within this conditioning paradigm, seated participants have to reduce the mechanically elicited reflex response using biofeedback of reflex magnitude quantified using electromyography (EMG). Before clinical application of the conditioning paradigm, improvements are needed regarding the time-intensiveness and slow learning curve. Previous studies have shown that gamification of biofeedback can improve participant motivation and long-term engagement. Moreover, quantification of reflex magnitude for biofeedback using reflexive joint impedance may obtain similar effectiveness within fewer sessions. Nine healthy volunteers participated in the study, split in three groups. First, as a reference the "Conventional" group received EMG- and bar-based biofeedback similar to previous research. Second, we explored feasibility of game-based biofeedback with the "Gaming" group receiving EMG- and game-based biofeedback. Third, we explored feasibility of game- and impedance-based biofeedback with the "Impedance" group receiving impedance and game-based biofeedback. Participants completed five baseline sessions (without reflex biofeedback) and six conditioning sessions (with reflex biofeedback). Participants were instructed to reduce reflex magnitude without modulating background activity. The Conventional and Gaming groups showed feasibility of the protocol in 2 and 3 out of 3 participants, respectively. These participants achieved a significant Soleus short-latency (M1) within-session reduction in at least -15% in the 4th-6th conditioning session. None of the Impedance group participants showed any within-session decrease in Soleus reflex magnitude. The feasibility in the EMG- and game-based biofeedback calls for further research on gamification of the conditioning paradigm to obtain improved participant motivation and engagement, while achieving long-term conditioning effects. Before clinical application, the time-intensiveness and slow learning curve of the conditioning paradigm remain an open challenge.

Estimation of Time-Varying Ankle Joint Stiffness Under Dynamic Conditions via System Identification Techniques.

An important goal in the design of next-generation exoskeletons and limb prostheses is to replicate human limb dynamics. Joint impedance determines the dynamic relation between joint displacement and torque. Joint stiffness is the position-dependent component of joint impedance and is key in postural control and movement. However, the mechanisms to modulate joint stiffness are not fully understood yet. The goal of this study is to conduct a systematic analysis on how humans modulate ankle stiffness. Time-varying stiffness was estimated for six healthy subjects under isometric, as well as quick and slow dynamic conditions via system identification techniques; specifically, an ensemble-based algorithm using short segments of ankle torque and position recordings. Our results show that stiffness had the lowest magnitude under quick dynamic conditions. Under isometric conditions, with fixed position and varying muscle activity, stiffness exhibited a higher magnitude. Finally, under slow dynamic conditions, stiffness was found to be the highest. Our results highlight, for the first time, the variability in stiffness modulation strategies across conditions, especially across movement velocity.

Model-Based Estimation of Ankle Joint Stiffness During Dynamic Tasks: a Validation-Based Approach.

Joint stiffness estimation under dynamic conditions still remains a challenge. Current stiffness estimation methods often rely on the external perturbation of the joint. In this study, a novel 'perturbation-free' stiffness estimation method via electromyography (EMG)-driven musculoskeletal modeling was validated for the first time against system identification techniques. EMG signals, motion capture, and dynamic data of the ankle joint were collected in an experimental setup to study the ankle joint stiffness in a controlled way, i.e. at a movement frequency of 0.6 Hz as well as in the presence and absence of external perturbations. The model-based joint stiffness estimates were comparable to system identification techniques. The ability to estimate joint stiffness at any instant of time, with no need to apply joint perturbations, might help to fill the gap of knowledge between the neural and the muscular systems and enable the subsequent development of tailored neurorehabilitation therapies and biomimetic prostheses and orthoses.