Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, and spastic paralysis due to involuntary muscle contraction in the hands and fingers can severely restrict skilled hand movements. However, the underlying neurological mechanisms remain unknown. Using a mouse model of spasticity after stroke, we demonstrate changes in neuronal activity with and without electrostimulation of the afferent nerve to induce the stretch reflex, measured using quantitative activation-induced manganese-enhanced magnetic resonance imaging. Neuronal activity increased within the ventral medullary reticular formation (MdV) in the contralesional brainstem during the acute post-stroke phase, and this increase was characterised by activation of circuits involved in spasticity. Interestingly, ascending electrostimulation inhibited the MdV activity on the stimulation side in normal conditions. Moreover, immunohistochemical staining showed that, in the acute phase, the density of GluA1, one of the α-amino-3 hydroxy‑5 methyl -4 isoxazolepropionic acid receptor (AMPAR) subunits, at the synapses of MdV neurons was significantly increased. In addition, the GluA1/GluA2 ratio in these receptors was altered at 2 weeks post-stroke, confirming homeostatic plasticity as the underlying mechanisms of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity at the acute post-stroke phase.

The primary motor cortex does not uniquely or directly produce alpha motoneurone (α-MN) drive to muscles during voluntary movement. Rather, α-MN drive emerges from the synthesis and competition among excitatory and inhibitory inputs from multiple descending tracts, spinal interneurons, sensory inputs, and proprioceptive afferents. One such fundamental input is velocity-dependent stretch reflexes in lengthening muscles, which should be inhibited to enable voluntary movement. It remains an open question, however, the extent to which unmodulated stretch reflexes disrupt voluntary movement, and whether and how they are inhibited in limbs with numerous multiarticular muscles. We used a computational model of a Rhesus Macaque arm to simulate movements with feedforward α-MN commands only, and with added velocity-dependent stretch reflex feedback. We found that velocity-dependent stretch reflex caused movement-specific, typically large and variable disruptions to arm movements. These disruptions were greatly reduced when modulating velocity-dependent stretch reflex feedback (i) as per the commonly proposed (but yet to be clarified) idealized alpha-gamma (α-γ) coactivation or (ii) an alternative α-MN collateral projection to homonymous γ-MNs. We conclude that such α-MN collaterals are a physiologically tenable propriospinal circuit in the mammalian fusimotor system. These collaterals could still collaborate with α-γ coactivation, and the few skeletofusimotor fibers (β-MNs) in mammals, to create a flexible fusimotor ecosystem to enable voluntary movement. By locally and automatically regulating the highly nonlinear neuro-musculo-skeletal mechanics of the limb, these collaterals could be a critical low-level enabler of learning, adaptation, and performance via higher-level brainstem, cerebellar, and cortical mechanisms.

The Tonic Stretch Reflex Threshold (TSRT) is the joint angle or muscle length (λ) at which muscle activation begins. In spasticity, the TSRT abnormally lies inside the biomechanical joint range. It is determined by measuring the Dynamic Stretch Reflex Thresholds (DSRTs) by stretching the resting muscle at different velocities. The metric μ, characterizes the velocity-sensitivity of the DSRTs and is expressed as the time required to lengthen the passive muscles from DSRT to TSRT at the respective stretch velocity. The original formulation of the TSRT, DSRT and μ is summarized. Then, a thorough search of literature prior to December 2023 was conducted that returned 25 papers that have used the technique. Eleven of these papers come from the research group of the authors, including 1 reporting on treatment effects. Of the remaining 14 papers, 11 report variations of the methodology with different populations and 3 report on the effects of an intervention. The review discusses how specific modifications to data collection and analysis procedures have either improved the methodology or, in some cases, led to uninterpretable results. The influence of modifications to the data collection and analysis procedures is discussed.

Reaching movements generally show smooth kinematic profiles that are invariant across varying movement speeds even as interaction torques and muscle properties vary nonlinearly with speed. How the brain brings about these invariant profiles is an open question. We developed an analytical inverse dynamics method to estimate descending activation patterns directly from observed joint angle trajectories based on a simple model of the stretch reflex, and of muscle and biomechanical dynamics. We estimated descending activation patterns for experimental data from eight different planar two-joint movements performed at two movement times (fast: 400 ms; slow: 800 ms). The temporal structure of descending activation differed qualitatively across speeds, consistent with the idea that the nervous system uses an internal model to generate anticipatory torques during fast movement. This temporal structure also depended on the cocontraction level of antagonistic muscle groups. Comparing estimated muscle activation and descending activation revealed the contribution of the stretch reflex to movement generation that was found to set in after about 20% of movement time.NEW & NOTEWORTHY By estimating descending activation patterns directly from observed movement kinematics based on a model of the dynamics of the stretch reflex, of muscle force generation, and of the biomechanics of the limb, we observed how brain signals must be temporally structured to enable fast movement.

BACKGROUND: Diabetic peripheral neuropathy is the most common complication of diabetes producing metabolic disruptions in the peripheral nervous system. Alteration in the predictable nature of tendon reflexes is the most common indicator suggesting the possibility of diabetic neuropathy. Evaluation of tendon reflexes is a part of various clinical scoring systems that assess neuropathy. The conventional reflex grading scales are subjective, lack temporal data, and have high inter-rater variability. Hence, an indigenous quantification tool was developed to evaluate the tendon reflexes in order to assess diabetic peripheral neuropathy.
METHODS: A cross-sectional study was carried out in 140 healthy volunteers and 140 patients with type 2 diabetes. The mean age of controls and diabetics (49.1 ± 8.9, 50.7 ± 7.5) years, weight (66.9 ± 9.4, 69.8 ± 11.5) kilograms and BMI (24.5 ± 3.8, 26.1 ± 4.7), respectively. All of them are subjected to evaluation of tendon reflexes using the reflex quantification tool comprised of surface mechanomyography and electrogoniometry that can provide various static and dynamic variables of tendon reflex.
RESULTS: The dynamic variables such as reflex amplitude, muscle velocity and angular velocity were significantly low in diabetic patients (p: <0.001) whereas latency and duration (p: <0.001) were prolonged. Furthermore, no significant difference was observed in the application of tendon striking force (p: 0.934) among the participants.
CONCLUSIONS: The current study demonstrates that the proposed reflex quantification tool provides several dynamic variables of patellar tendon reflex, which are significantly affected and altered in diabetic patients suggesting the involvement of peripheral neurons.

Amyotrophic lateral sclerosis (ALS) diagnosis relies on signs of progressive damage to both lower motoneuron (LMN), given by clinical examination and electromyography (EMG), and upper motoneuron (UMN), given by clinical examination only. Recognition of UMN involvement, however, is still difficult, so that diagnostic delay often remains too long. Shortening the time to clinical and genetic diagnosis is essential in order to provide accurate information to patients and families, avoid time-consuming investigations and for appropriate care management. This study investigates whether combined patellar tendon reflex recording with motor-evoked potentials to the lower limbs (T-MEP-LL) is relevant to assess corticospinal function in ALS, so that it might serve as a tool improving diagnosis. T-MEP-LL were recorded in 135 patients with suspected motor neuron disease (MND) from February 2010 to March 2021. The sensitivity, specificity, and ability to improve diagnosis when added to Awaji and Gold Coast criteria were determined. The main finding of the study is that T-MEP-LL can detect UMN dysfunction with a 70% sensitivity and 63% specificity when UMN clinical signs are lacking. The sensitivity reaches 82% when considering all MND patients. Moreover, at first evaluation, using T-MEP-LL to quantify reflex briskness and to measure central conduction time, can improve the diagnostic accuracy. T-MEP-LL is easy to perform and does not need any electrical stimulation, making the test rapid, and painless. By the simultaneous quantification of both UMN and LMN system, it could also help to identify different phenotype with more accuracy than clinical examination in this broad-spectrum pathology. The question whether T-MEP-LL could further be a real biomarker need further prospective studies.

Spasticity attributable to exaggerated stretch reflex pathways, particularly affecting the ankle plantar flexors, often impairs overground walking in persons with incomplete spinal cord injury. Compelling evidence from rodent models underscores how exposure to acute intermittent hypoxia (AIH) can provide a unique medium to induce spinal plasticity in key inhibitory pathways mediating stretch reflex excitability and potentially affect spasticity. In this study, we quantify the effects of a single exposure to AIH on the stretch reflex in able-bodied individuals. We hypothesized that a single sequence of AIH will increase the stretch reflex excitability of the soleus muscle during ramp-and-hold angular perturbations applied to the ankle joint while participants perform passive and volitionally matched contractions. Our results revealed that a single AIH exposure did not significantly change the stretch reflex excitability during both passive and active matching conditions. Furthermore, we found that able-bodied individuals increased their stretch reflex response from passive to active matching conditions after both sham and AIH exposures. Together, these findings suggest that a single AIH exposure might not engage inhibitory pathways sufficiently to alter stretch reflex responses in able-bodied persons. However, the generalizability of our present findings requires further examination during repetitive exposures to AIH along with potential reflex modulation during functional movements, such as overground walking.

Arthrogenic muscle inhibition (AMI) is induced by pathological knee conditions. The present study aimed to investigate the effect of tactile stimulation on reflex changes induced by simulated AMI during unpredictable landing performances. Twenty participants performed six unilateral landing tasks: 15 cm normal landing (15NL), 30 cm normal landing (30NL), surprise landing (SL), 30 cm normal landing following vibration (30NLV), SL following vibration (SLV), and SL following vibration with Kinesiology tape (SLK). For SL, the solid landing platform (15 cm) was removed and replaced by a false floor. Since the false floor dislodged easily under load, participants unpredictably fell through the platform to the actual landing surface 15 cm below. After completing 15NL, 30NL, and SL, vibration was applied to participants\' knees to induce neurological changes similar to AMI. After vibration, participants performed 30NLV, SLV, and SLK in a random order. EMG signals in the post-landing short latency (31-60 ms) and medium latency (61-90 ms) periods were examined. EMG signals from the vastus lateralis (VL), vastus medialis (VM), and biceps femoris (BF) were recorded and compared between tasks. EMG signals of all muscles in SL were significantly enhanced in the medium latency period as compared with 30NL. Enhanced EMG signals in SL were suppressed by vibration stimulation in the VL, but the suppressed EMG signals were restored after cutaneous stimulation with Kinesiology tape (p < 0.01). Our findings suggest that AMI could alter motor control patterns during unpredictable landing and that tactile stimulation could restore the altered motor control to a normal state.

Spasticity might affect gait in children with cerebral palsy. Quantifying its occurrence during locomotion is challenging. One approach is to determine kinematic stretch reflex thresholds, usually on the velocity, during passive assessment and to search for their exceedance during gait. These thresholds are determined through EMG-Onset detection algorithms, which are variable in performance and sensitive to noisy data, and can therefore lack consistency. This study aimed to evaluate the feasibility of determining the velocity stretch reflex threshold from maximal musculotendon acceleration. Eighteen children with CP were recruited and underwent clinical gait analysis and a full instrumented assessment of their soleus, gastrocnemius lateralis, semitendinosus, and rectus femoris spasticity, with EMG, kinematics, and applied forces being measured simultaneously. Using a subject-scaled musculoskeletal model, the acceleration-based stretch reflex velocity thresholds were determined and compared to those based on EMG-Onset determination. Their consistencies according to physiological criteria, i.e., if the timing of the threshold was between the beginning of the stretch and the spastic catch, were evaluated. Finally, two parameters designed to evaluate the occurrence of spasticity during gait, i.e., the proportion of the gait trial time with a gait velocity above the velocity threshold and the number of times the threshold was exceeded, were compared. The proposed method produces velocity stretch reflex thresholds close to the EMG-based ones. For all muscles, no statistical difference was found between the two parameters designed to evaluate the occurrence of spasticity during gait. Contrarily to the EMG-based methods, the proposed method always provides physiologically consistent values, with median electromechanical delays of between 50 and 130 ms. For all subjects, the semitendinosus velocity during gait usually exceeded its stretch reflex threshold, while it was less frequent for the three other muscles. We conclude that a velocity stretch reflex threshold, based on musculotendon acceleration, is a reliable substitute for EMG-based ones.

Spasticity is characterized by a velocity-dependent increase in the tonic stretch reflex. Evidence suggests that spasticity originates from hyperactivity in the descending tract or reflex loop. To pinpoint the source of hyperactivity, however, is difficult due to lack of human data in-vivo. Thus, we implemented a neuromorphic model to revive the neurodynamics with spiking neuronal activity. Two types of input were modeled: (1) the additive condition (ADD) to apply tonic synaptic inputs directly into the reflex loop; (2) the multiplicative (MUL) condition to adjust the loop gains within the reflex loop. Results show that both conditions produced antagonist EMG responses resembling patient data. The timing of spasticity is more sensitive to the ADD condition, whereas the amplitude of spastic EMG is more sensitive to the MUL condition. In conclusion, our model shows that both additive and multiplicative hyperactivities suffice to elicit velocity-dependent spastic electromyographic signals (EMG), but with different sensitivities. This simulation study suggests that spasticity caused by different origins may be discernable by the progression of severity, which may help individualized goalsetting and parameter-selection in rehabilitation.Clinical Relevance-Potential application of neuromorphic modeling on spasticity includes selection of parameters for therapeutic plans, such as movement range, repetition, and load.