Spinal Stretch Reflex Research Articles

Self-modulation of rectus femoris reflex excitability in humans

Hyperreflexia is common after neurological injury such as stroke, yet clinical interventions have had mixed success. Our previous research has shown that hyperreflexia of the rectus femoris (RF) during pre-swing is closely associated with reduced swing phase knee flexion in those with post-stroke Stiff-Knee gait (SKG). Thus, reduction of RF hyperreflexia may improve walking function in those with post-stroke SKG. A non-pharmacological procedure for reducing hyperreflexia has emerged based on operant conditioning of H-reflex, an electrical analog of the spinal stretch reflex. It is currently unknown whether operant conditioning can be applied to the RF. This feasibility study trained 7 participants (5 neurologically intact, 2 post-stroke) to down-condition the RF H-reflex using visual feedback. We found an overall decrease in average RF H-reflex amplitude among all 7 participants (44% drop, p < 0.001, paired t-test), of which the post-stroke individuals contributed (49% drop). We observed a generalized training effect across quadriceps muscles. Post-stroke individuals exhibited improvements in peak knee-flexion velocity, reflex excitability during walking, and clinical measures of spasticity. These outcomes provide promising initial results that operant RF H-reflex conditioning is feasible, encouraging expansion to post-stroke individuals. This procedure could provide a targeted alternative in spasticity management.

Molecular Identification of Pro-Excitogenic Receptor and Channel Phenotypes of the Deafferented Lumbar Motoneurons in the Early Phase after SCT in Rats.

Spasticity impacts the quality of life of patients suffering spinal cord injury and impedes the recovery of locomotion. At the cellular level, spasticity is considered to be primarily caused by the hyperexcitability of spinal α-motoneurons (MNs) within the spinal stretch reflex circuit. Here, we hypothesized that after a complete spinal cord transection in rats, fast adaptive molecular responses of lumbar MNs develop in return for the loss of inputs. We assumed that early loss of glutamatergic afferents changes the expression of glutamatergic AMPA and NMDA receptor subunits, which may be the forerunners of the developing spasticity of hindlimb muscles. To better understand its molecular underpinnings, concomitant expression of GABA and Glycinergic receptors and serotoninergic and noradrenergic receptors, which regulate the persistent inward currents crucial for sustained discharges in MNs, were examined together with voltage-gated ion channels and cation-chloride cotransporters. Using quantitative real-time PCR, we showed in the tracer-identified MNs innervating extensor and flexor muscles of the ankle joint multiple increases in transcripts coding for AMPAR and 5-HTR subunits, along with a profound decrease in GABAAR, GlyR subunits, and KCC2. Our study demonstrated that both MNs groups similarly adapt to a more excitable state, which may increase the occurrence of extensor and flexor muscle spasms.

Spinal stretch reflexes support efficient control of reaching.

Efficiently controlling the movement of our hand requires coordinating the motion of multiple joints of the arm. Although it is widely assumed that this type of efficient control is implemented by processing that occurs in the cerebral cortex and brainstem, recent work has shown that spinal circuits can generate efficient motor output that supports keeping the hand in a static location. Here, we show that a spinal pathway can also efficiently control the hand during reaching. In our first experiment, we applied multijoint mechanical perturbations to participants' elbow and wrist as they began reaching toward a target. We found that spinal stretch reflexes evoked in elbow muscles were not proportional to how much the elbow muscles were stretched but instead were dependent on the hand's location relative to the target. In our second experiment, we applied the same elbow and wrist perturbations but had participants change how they grasped the manipulandum, diametrically altering how the same wrist perturbation moved the hand relative to the reach target. We found that changing the arm's orientation diametrically altered how spinal reflexes in the elbow muscles were evoked, and in such a way that were again dependent on the hand's location relative to the target. These findings demonstrate that spinal circuits can help efficiently control the hand during dynamic reaching actions and show that efficient and flexible motor control is not exclusively dependent on processing that occurs within supraspinal regions of the nervous system.NEW & NOTEWORTHY We have previously shown that spinal circuits can rapidly generate reflex responses that efficiently engage multiple joints to support postural hand control of the upper limb. Here, we show that spinal circuits can also rapidly generate such efficient responses during reaching actions.

The Effect of Cold on the Trigeminal Reflexes

Objective: Effects of muscle cooling on the spinal stretch and monosynaptic reflexes have been studied to describe the properties of Group I and II afferents of muscle spindles. Masseter muscle differs from extremity muscles in structural and numerical features of the muscle spindles. The aim of this study was to examine the muscle spindle afferent features of masseter muscle by applying cold to understand the role of Group I and II afferents in reflexes of masseter. Patients and Methods: We included 12 healthy subjects (7 females and 5 males) in the study. Masseter inhibitory reflex (MIR), jaw tendon reflex (JTR), trigeminal motor evoked potential (MEP), and trigeminal somatosensory evoked potential (SEP) were studied before and after cold application. Left masseter muscle was cooled down to 18°C. We compared the data obtained before and after cold application. Results: After cold application, the mean total duration of MIR was shortened and it was absent in four subjects. The mean amplitude of JTR was higher after cold application (P = 0.018) without any significant change in latency. The mean latency of MEP was delayed without any change in amplitude (P = 0.003). There was no significant difference in SEPs. Conclusions: Changes observed in MIR, JTR, and MEP could not be ascribed to any specific type of muscle spindle afferents. Delayed mean reflex latencies were attributed to the effect of cold on nerve conduction. Summation of peripheral cold and pain receptor features, spindle afferents, and cortical mechanisms might have caused cold-associated changes.

Assessing Neural Connectivity and Associated Time Delays of Muscle Responses to Continuous Position Perturbations.

Both linear and nonlinear electromyographic (EMG) connectivity has been reported during the expression of stretch reflexes, though it is not clear whether they are generated by the same neural pathways. To answer this question, we aim to distinguish linear and nonlinear connectivity, as well as their delays in muscle responses, resulting from continuous elbow joint perturbations. We recorded EMG from Biceps Brachii muscle when eight able-bodied participants were performing a steady elbow flexion torque while simultaneously receiving a continuous position perturbation. Using a recently developed phase coupling metric, we estimated linear and nonlinear connectivity as well as their associated delays between Biceps EMG responses and perturbations. We found that the time delay for linear connectivity (24.5 ± 5.4ms) is in the range of short-latency stretch reflex period (< 35ms), while that for nonlinear connectivity (53.8 ± 3.2ms) is in the range of long-latency stretch reflex period (40-70ms). These results suggest that the estimated linear connectivity between EMG and perturbations is very likely generated by the mono-synaptic spinal stretch reflex loop, while the nonlinear connectivity may be associated with multi-synaptic supraspinal stretch reflex loops. As such, this study provides new evidence of the nature of neural connectivity related to the stretch reflex.

Upregulation of spinal stretch reflexes during upper-limb posture control task

Background: Sensory feedback from receptors in the eyes, skin, vestibular organs and muscles allows us to build accurate representations of the position and motion of our body within the environment. In unpredictable situations, such as when holding an umbrella in gusting winds, studies have suggested the nervous system upregulates the sensitivity of sensory organs to counter disturbances and increase the probability of success. To date, studies have focused exclusively on the upregulation of feedback mechanisms in the lower-limbs during standing balance. We know comparatively little about whether and how sensory upregulation contributes to the control of upper limb motor actions.&#x0D; Objectives: Examine the upregulation and adaptation of upper limb muscle activity and spinal stretch reflexes when interacting with unpredictable mechanical environments.&#x0D; Methods: Ten healthy, right-handed adults (age range: 20 – 27 years) performed a postural control task where the goal was to maintain their hand within a fixed target. Participants performed the task while seated with their arm supported in an exoskeleton robot that can sense and disturb arm motion. They received real-time feedback of their movements on a virtual reality system. The protocol was delivered in three phases. The baseline phase consisted of 50 trials where subjects maintained their hand in the target in the absence of mechanical disturbances. Subjects then performed a peri-exposure phase that consisted of 100 null trials (no forces applied), 100 step-torque perturbations that produced rapid elbow flexion (+2Nm), and 100 perturbations that caused rapid elbow extension (-2Nm). We then unexpectedly removed the perturbations and subjects performed 75 trials to determine whether muscle activity returned to baseline levels. Kinematics and muscle activity were recorded throughout the experiment.&#x0D; Results: Preliminary results show that background muscle activity and spinal stretch reflexes were the largest when first exposed to unpredictable mechanical perturbations and adapted systematically with repeated exposure.&#x0D; Conclusions: Similar to results observed in the lower-limbs during standing balance experiments, we observed upregulation of background muscle activity and spinal stretch reflexes when interacting with unpredictable mechanical environments with the upper-limb. The amplitude of spinal stretch responses and background muscle activity decayed systematically with repeated exposure to unpredictable mechanical perturbations.

Acquisition of a simple motor skill: task-dependent adaptation and long-term changes in the human soleus stretch reflex.

Changing the H reflex through operant conditioning leads to CNS multisite plasticity and can affect previously learned skills. To further understand the mechanisms of this plasticity, we operantly conditioned the initial component (M1) of the soleus stretch reflex. Unlike the H reflex, the stretch reflex is affected by fusimotor control, comprises several bursts of activity resulting from temporally dispersed afferent inputs, and may activate spinal motoneurons via several different spinal and supraspinal pathways. Neurologically normal participants completed 6 baseline sessions and 24 operant conditioning sessions in which they were encouraged to increase (M1up) or decrease (M1down) M1 size. Five of eight M1up participants significantly increased M1; the final M1 size of those five participants was 143 ± 15% (mean ± SE) of the baseline value. All eight M1down participants significantly decreased M1; their final M1 size was 62 ± 6% of baseline. Similar to the previous H-reflex conditioning studies, conditioned reflex change consisted of within-session task-dependent adaptation and across-session long-term change. Task-dependent adaptation was evident in conditioning session 1 with M1up and by session 4 with M1down. Long-term change was evident by session 10 with M1up and by session 16 with M1down. Task-dependent adaptation was greater with M1up than with the previous H-reflex upconditioning. This may reflect adaptive changes in muscle spindle sensitivity, which affects the stretch reflex but not the H reflex. Because the stretch reflex is related to motor function more directly than the H reflex, M1 conditioning may provide a valuable tool for exploring the functional impact of reflex conditioning and its potential therapeutic applications. NEW & NOTEWORTHY Since the activity of stretch reflex pathways contributes to locomotion, changing it through training may improve locomotor rehabilitation in people with CNS disorders. Here we show for the first time that people can change the size of the soleus spinal stretch reflex through operant conditioning. Conditioned stretch reflex change is the sum of task-dependent adaptation and long-term change, consistent with H-reflex conditioning yet different from it in the composition and amount of the two components.

Sustained involuntary muscle activity in cerebral palsy and stroke: same symptom, diverse mechanisms.

Individuals with lesions of central motor pathways frequently suffer from sustained involuntary muscle activity. This symptom shares clinical characteristics with dystonia but is observable in individuals classified as spastic. The term spastic dystonia has been introduced, although the underlying mechanisms of involuntary activity are not clarified and vary between individuals depending on the disorder. This study aimed to investigate the nature and pathophysiology of sustained involuntary muscle activity in adults with cerebral palsy and stroke. Seventeen adults with cerebral palsy (Gross Motor Function Classification System I–V), 8 adults with chronic stroke and 14 control individuals participated in the study. All individuals with cerebral palsy or stroke showed increased resistance to passive movement with Modified Ashworth Scale >1. Two-minute surface EMG recordings were obtained from the biceps muscle during attempted rest in three positions of the elbow joint; a maximally flexed position, a 90-degree position and a maximally extended position. Cross-correlation analysis of sustained involuntary muscle activity from individuals with cerebral palsy and stroke, and recordings of voluntary isometric contractions from control individuals were performed to examine common synaptic drive. In total, 13 out of 17 individuals with cerebral palsy and all 8 individuals with stroke contained sustained involuntary muscle activity. In individuals with cerebral palsy, the level of muscle activity was not affected by the joint position. In individuals with stroke, the level of muscle activity significantly (P < 0.05) increased from the flexed position to the 90 degree and extended position. Cumulant density function indicated significant short-term synchronization of motor unit activities in all recordings. All groups exhibited significant coherence in the alpha (6–15 Hz), beta (16–35 Hz) and early gamma band (36–60 Hz). The cerebral palsy group had lower alpha band coherence estimates, but higher gamma band coherence estimates compared with the stroke group. Individuals with increased resistance to passive movement due to cerebral palsy or stroke frequently suffer sustained involuntary muscle activity, which cannot exclusively be described by spasticity. The sustained involuntary muscle activity in both groups originated from a common synaptic input to the motor neuron pool, but the generating mechanisms could differ between groups. In cerebral palsy it seemed to originate more from central mechanisms, whereas peripheral mechanisms likely play a larger role in stroke. The sustained involuntary muscle activity should not be treated simply like the spinal stretch reflex mediated symptom of spasticity and should not either be treated identically in both groups.

The Effects of Acute Lipopolysaccharide Induced Inflammation on Spinal Cord Excitability

Peripheral inflammation alters the excitability of dorsal horn interneurons and increases flexor reflex strength (Dubner & Ruda, 1992); however, its effect on the spinal stretch reflex is not well understood. The stretch reflex is a muscle contraction in response to muscle stretch. We hypothesize that the acute inflammation caused by an injection of lipopolysaccharide (LPS) will cause an increase in spinal cord excitability. To test this hypothesis, we measured Hoffman’s (H) reflex, the electric analog of the stretch reflex in adult mice receiving an injection of LPS (.5mg/kg) or saline (200μl). Adult male and female mice (C57Bl/6) were anesthetized; then, the sciatic nerve was exposed and stimulated at current strengths from H-wave threshold (T) to 8T (20 x 0.1 ms pulses at 0.1 Hz). Recording electrodes were placed in the foot. We measured the maximum M wave amplitude (Mmax), maximum H wave amplitude (Hmax) and latencies of both waves. We compared the ratio of the maximal H wave over the maximal M wave (Hmax/Mmax), which reports the percentage of motor neurons activated by electrical stimulation of Group Ia muscle sensory neurons. Increased spinal cord excitability would be reflected in a larger Hmax/Mmax. We found that LPS-induced inflammation does not alter the Hmax/Mmax. While we found no evidence of changes in spinal cord excitability, inflammation could be altering Group Ia muscle spindle afferent responses to stretch. Future studies will test whether stretch reflex strength is altered by inflammation.

Characteristics of Rest and Postural Tremors in Parkinson's Disease: An Analysis of Motor Unit Firing Synchrony and Patterns.

The neural mechanisms responsible for resting and postural tremor in Parkinson’s disease (PD) have been the object of considerable study, much of it focusing on supraspinal sites. Here, we adopted an alternative approach that emphasizes motor unit (MU) firing synchrony and patterns of discharge. To explore if these could account for known features of PD tremor, we recorded the instantaneous acceleration of the upper limb of 23 PD patients at rest or while they tried to hold a stable posture together with surface EMG and single MU discharges of upper limb muscles. Spectral, coherence and cross-correlation analyses of the recorded signals demonstrated alternating epoch-I and epoch-II intervals in PD patients both at rest and while they held a stable posture. Epoch-II intervals are characterized by the presence of 4–8 Hz overt tremor, enhanced MU synchrony and spike-doublets or triplets bearing a one-to-one relation to each tremor cycle. Epoch-I resembled physiological tremor in that it was characterized by 6–10 Hz non-overt tremor, lower MU synchrony and rhythmical MU firing at the intrinsic rate of the unit. The frequency of overt and non-overt tremor remained the same whether the patient was at rest or held a stable posture and the same was true of the remaining characteristics of epoch-I and epoch-II. The mean interval between spikes of a doublet/triplet varied between 30 and 50 ms and, for any given patient, remained roughly constant throughout measurements. This is the first time that enhanced MU synchrony and spike doublets/triplets characterized by relatively stable interspike intervals, are shown to accompany the overt tremor of PD patients. To account for our findings we propose that a two-state oscillatory spinal stretch reflex loop generates overt parkinsonian tremor in response to intermittent, descending, relatively high frequency oscillatory signals.

Role of axial and support unloading in development of hypogravitational motor syndrome

Event Abstract Back to Event Role of axial and support unloading in development of hypogravitational motor syndrome Elena S. Tomilovskaya1*, Ilya V. Rukavishnikov1, Tatiana A. Shigueva1, Tatyana B. Kukoba1, Inna S. Sosnina1, Lyubov E. Amirova1 and Inessa B. Kozlovskaya1 1 Institute of Biomedical Problems (RAS), Russia Dry Immersion (DI) studies that were performed for years at the Institute of Biomedical Problems have shown that support withdrawal is followed by the development of hypogravitational motor syndrome signs (HMS), similar to those observed after space flights: postural muscle atonia and atrophy, hyperreflexia of spinal reflexes, voluntary movement discoordination, postural and locomotor alterations, back pain etc. (Kozlovskaya et al., 1988; 2007; Miller et al., 2004; Shenkman et al., 2017). Daily mechanical stimulation of the soles during DI eliminates the mentioned effects almost to full extent (Grigoriev et al., 2004; Kozlovskaya et al., 2007). Basing on these results it was concluded that support afferentation plays the role of trigger in development of HMS. However it is necessary to take into account that withdrawal of weight in weightlessness and DI is followed not only by supportlessness but also by axial unloading. So the aim of this work was to study the effects of supportlessness coupled with axial loading to define the role of axial load on HMS development. Twenty healthy volunteers divided into 2 groups took part in the study. No influences except 5-days DI was used in the group which served as a control. The subjects of experimental group in DI every day for 4 hours were wearing "Penguin" axial loading suit that provided the 16-18 kg axial load on the body – from the shoulders to the ankles. Parameters of the postural and locomotor activities, the spinal stretch reflexes, the accuracy of voluntary movements, intervertebral discs height, back pain intensity, tone and force-velocity properties of leg and back muscles have been studied. All the mentioned signs of HMS were observed in the control group: the tone of postural muscles sharply decreased, hypereflexia of stretch reflexes was observed, muscle strength and endurance decreased, postural stability was altered, voluntary movement coordination declined. Results of the experiments confirmed our previous suggestion that muscular atonia provides the development of movement disorders, back pain and other phenomena such as increase of height, elongation of the spine and height of intervertebral disks, etc. (Rukavishnikov et al., 2016; Treffel et al., 2016). Back extensor muscles atonia and significant increase in the intervertebral disk height were registered in the lumbar spine projection; at the same localization all test subjects reported the symptoms of back pain. In the experimental group the intensity of back pain was significantly lower (p=0.0028 for DI1, p=0.006 for DI2 and p=0.0004 for DI3 – by ANOVA repeated measures with Bonferroni correction) (Fig.1). Figure 1. Back pain intensity in the course of Dry Immersion in 2 groups. * - significant difference compared to the baseline; @ - significant difference between groups (p<0.01). Height increase and the decline of force-velocity properties of back and neck muscles were also significantly lower than in the group without countermeasures (p<0.05). However for the leg muscles the changes were similar to the control group. Spinal reflex facilitation (Fig.2), accuracy of hand voluntary movements’ decrease and other HMS signs were not significant in this group. Slight tendency to H-reflex threshold decrease was registered in this group, however the changes were not significant (p=0.062). Figure 2. Changes of spinal reflex characteristics in 2 groups in the course of Dry Immesion. A – Changes in the threshold of H-reflex; B – Changes in peak amplitude of H-response. Blue lines – the group of “pure” immersion with no countermeasures; red dotted lines – the group of 4 hours daily axial loading in the course of Dry immersion. * - p<0.05 compared to baseline values; @ - significant difference between group (p<0.05). There were not revealed significant difference between groups in parameters of postural and locomotor coordination. The results of the study have shown that axial unloading in microgravity plays significant role in development of HMS. However it reveals more tight connections of avail loading to muscles of the body when the support reactions are involved to a great extent in the control of leg muscles state and locomotor and postural functions. Figure 1 Figure 2 Acknowledgements The study is supported by RFBR № 16-29-08320-OFI-m.

Nonlinear Connectivity in the Human Stretch Reflex Assessed by Cross-Frequency Phase Coupling.

Communication between neuronal populations is facilitated by synchronization of their oscillatory activity. Although nonlinearity has been observed in the sensorimotor system, its nonlinear connectivity has not been widely investigated yet. This study investigates nonlinear connectivity during the human stretch reflex based on neuronal synchronization. Healthy participants generated isotonic wrist flexion while receiving a periodic mechanical perturbation to the wrist. Using a novel cross-frequency phase coupling metric, we estimate directional nonlinear connectivity, including time delay, from the perturbation to brain and to muscle, as well as from brain to muscle. Nonlinear phase coupling is significantly stronger from the perturbation to the muscle than to the brain, with a shorter time delay. The time delay from the perturbation to the muscle is 33 ms, similar to the reported latency of the spinal stretch reflex at the wrist. Source localization of nonlinear phase coupling from the brain to the muscle suggests activity originating from the motor cortex, although its effect on the stretch reflex is weak. As such nonlinear phase coupling between the perturbation and muscle activity is dominated by the spinal reflex loop. This study provides new evidence of nonlinear neuronal synchronization in the stretch reflex at the wrist joint with respect to spinal and transcortical loops.

New insights into the pathophysiology of post-stroke spasticity.

Spasticity is one of many consequences after stroke. It is characterized by a velocity-dependent increase in resistance during passive stretch, resulting from hyperexcitability of the stretch reflex. The underlying mechanism of the hyperexcitable stretch reflex, however, remains poorly understood. Accumulated experimental evidence has supported supraspinal origins of spasticity, likely from an imbalance between descending inhibitory and facilitatory regulation of spinal stretch reflexes secondary to cortical disinhibition after stroke. The excitability of reticulospinal (RST) and vestibulospinal tracts (VSTs) has been assessed in stroke survivors with spasticity using non-invasive indirect measures. There are strong experimental findings that support the RST hyperexcitability as a prominent underlying mechanism of post-stroke spasticity. This mechanism can at least partly account for clinical features associated with spasticity and provide insightful guidance for clinical assessment and management of spasticity. However, the possible role of VST hyperexcitability cannot be ruled out from indirect measures. In vivo measure of individual brainstem nuclei in stroke survivors with spasticity using advanced fMRI techniques in the future is probably able to provide direct evidence of pathogenesis of post-stroke spasticity.

Electrocorticographic activity over sensorimotor cortex and motor function in awake behaving rats.

Sensorimotor cortex exerts both short-term and long-term control over the spinal reflex pathways that serve motor behaviors. Better understanding of this control could offer new possibilities for restoring function after central nervous system trauma or disease. We examined the impact of ongoing sensorimotor cortex (SMC) activity on the largely monosynaptic pathway of the H-reflex, the electrical analog of the spinal stretch reflex. In 41 awake adult rats, we measured soleus electromyographic (EMG) activity, the soleus H-reflex, and electrocorticographic activity over the contralateral SMC while rats were producing steady-state soleus EMG activity. Principal component analysis of electrocorticographic frequency spectra before H-reflex elicitation consistently revealed three frequency bands: μβ (5-30 Hz), low γ (γ1; 40-85 Hz), and high γ (γ2; 100-200 Hz). Ongoing (i.e., background) soleus EMG amplitude correlated negatively with μβ power and positively with γ1 power. In contrast, H-reflex size correlated positively with μβ power and negatively with γ1 power, but only when background soleus EMG amplitude was included in the linear model. These results support the hypothesis that increased SMC activation (indicated by decrease in μβ power and/or increase in γ1 power) simultaneously potentiates the H-reflex by exciting spinal motoneurons and suppresses it by decreasing the efficacy of the afferent input. They may help guide the development of new rehabilitation methods and of brain-computer interfaces that use SMC activity as a substitute for lost or impaired motor outputs.

Targeted neuroplasticity for rehabilitation.

An operant-conditioning protocol that bases reward on the electromyographic response produced by a specific CNS pathway can change that pathway. For example, in both animals and people, an operant-conditioning protocol can increase or decrease the spinal stretch reflex or its electrical analog, the H-reflex. Reflex change is associated with plasticity in the pathway of the reflex as well as elsewhere in the spinal cord and brain. Because these pathways serve many different behaviors, the plasticity produced by this conditioning can change other behaviors. Thus, in animals or people with partial spinal cord injuries, appropriate reflex conditioning can improve locomotion. Furthermore, in people with spinal cord injuries, appropriate reflex conditioning can trigger widespread beneficial plasticity. This wider plasticity appears to reflect an iterative process through which the multiple behaviors in the individual's repertoire negotiate the properties of the spinal neurons and synapses that they all use. Operant-conditioning protocols are a promising new therapeutic method that could complement other rehabilitation methods and enhance functional recovery. Their successful use requires strict adherence to appropriately designed procedures, as well as close attention to accommodating and engaging the individual subject in the conditioning process.

Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury.

Hyperreflexia and spasticity are chronic complications in spinal cord injury (SCI), with limited options for safe and effective treatment. A central mechanism in spasticity is hyperexcitability of the spinal stretch reflex, which presents symptomatically as a velocity-dependent increase in tonic stretch reflexes and exaggerated tendon jerks. In this study we tested the hypothesis that dendritic spine remodeling within motor reflex pathways in the spinal cord contributes to H-reflex dysfunction indicative of spasticity after contusion SCI. Six weeks after SCI in adult Sprague-Dawley rats, we observed changes in dendritic spine morphology on α-motor neurons below the level of injury, including increased density, altered spine shape, and redistribution along dendritic branches. These abnormal spine morphologies accompanied the loss of H-reflex rate-dependent depression (RDD) and increased ratio of H-reflex to M-wave responses (H/M ratio). Above the level of injury, spine density decreased compared with below-injury spine profiles and spine distributions were similar to those for uninjured controls. As expected, there was no H-reflex hyperexcitability above the level of injury in forelimb H-reflex testing. Treatment with NSC23766, a Rac1-specific inhibitor, decreased the presence of abnormal dendritic spine profiles below the level of injury, restored RDD of the H-reflex, and decreased H/M ratios in SCI animals. These findings provide evidence for a novel mechanistic relationship between abnormal dendritic spine remodeling in the spinal cord motor system and reflex dysfunction in SCI.

Operant conditioning of the soleus H-reflex does not induce long-term changes in the gastrocnemius H-reflexes and does not disturb normal locomotion in humans.

In normal animals, operant conditioning of the spinal stretch reflex or the H-reflex has lesser effects on synergist muscle reflexes. In rats and people with incomplete spinal cord injury (SCI), soleus H-reflex operant conditioning can improve locomotion. We studied in normal humans the impact of soleus H-reflex down-conditioning on medial (MG) and lateral gastrocnemius (LG) H-reflexes and on locomotion. Subjects completed 6 baseline and 30 conditioning sessions. During conditioning trials, the subject was encouraged to decrease soleus H-reflex size with the aid of visual feedback. Every sixth session, MG and LG H-reflexes were measured. Locomotion was assessed before and after conditioning. In successfully conditioned subjects, the soleus H-reflex decreased 27.2%. This was the sum of within-session (task dependent) adaptation (13.2%) and across-session (long term) change (14%). The MG H-reflex decreased 14.5%, due mainly to task-dependent adaptation (13.4%). The LG H-reflex showed no task-dependent adaptation or long-term change. No consistent changes were detected across subjects in locomotor H-reflexes, EMG activity, joint angles, or step symmetry. Thus, in normal humans, soleus H-reflex down-conditioning does not induce long-term changes in MG/LG H-reflexes and does not change locomotion. In these subjects, task-dependent adaptation of the soleus H-reflex is greater than it is in people with SCI, whereas long-term change is less. This difference from results in people with SCI is consistent with the fact that long-term change is beneficial in people with SCI, since it improves locomotion. In contrast, in normal subjects, long-term change is not beneficial and may necessitate compensatory plasticity to preserve satisfactory locomotion.

S11-3. Neurophysiological basis of body-weight supported step training

The body-weight supported step training (BWSS) has been originally applied to individuals with spinal cord injury (SCI) on the basis of numerous experimental evidences indicating that the central pattern generator (CPG) of quadruped animals can be reorganized and allows those animals walk independently after BWSS training. However, beside the fact that the CPG alone cannot provide full weight-bearing force and stepping in human, it is not known whether the other factors such as central command and sensory afferent information are involved in restoration of bipedal walking especially after incomplete SCI. To address this issue we have conducted a series of experiments, which aimed to reveal effects of both sensory inputs and descending commands on excitability modulation of neural circuits involving human bipedal locomotion. By using the Lokomat robotic gait trainer, we tested effects of sensory inputs on corticospinal (CS) excitabilities during assisted stepping. The results so far demonstrate that sensory inputs, especially body-weight related somatosensory input, have a facilitatory effect on CS pathway of an ankle flexor muscle, whereas those sensory inputs regardless of body-weight related or not have an inhibitory effect on spinal stretch reflex circuits of upper and lower limb muscles during the assisted stepping.

Effects of postural threat on spinal stretch reflexes: evidence for increased muscle spindle sensitivity?

Standing balance is often threatened in everyday life. These threats typically involve scenarios in which either the likelihood or the consequence of falling is higher than normal. When cats are placed in these scenarios they respond by increasing the sensitivity of muscle spindles imbedded in the leg muscles, presumably to increase balance-relevant afferent information available to the nervous system. At present, it is unknown whether humans also respond to such postural threats by altering muscle spindle sensitivity. Here we present two studies that probed the effects of postural threat on spinal stretch reflexes. In study 1 we manipulated the threat associated with an increased consequence of a fall by having subjects stand at the edge of an elevated surface (3.2 m). In study 2 we manipulated the threat by increasing the likelihood of a fall by occasionally tilting the support surface on which subjects stood. In both scenarios we used Hoffmann (H) and tendon stretch (T) reflexes to probe the spinal stretch reflex circuit of the soleus muscle. We observed increased T-reflex amplitudes and unchanged H-reflex amplitudes in both threat scenarios. These results suggest that the synaptic state of the spinal stretch reflex is unaffected by postural threat and that therefore the muscle spindles activated in the T-reflexes must be more sensitive in the threatening conditions. We propose that this increase in sensitivity may function to satisfy the conflicting needs to restrict movement with threat, while maintaining a certain amount of sensory information related to postural control.

Detection of knee‐joint motions using two linear accelerometers for pendulum test

AbstractIn order to solve nonlinear differential equations concerning spinal stretch reflexes in the pendulum test, mutually synchronized values of the angle, angular velocity, and angular acceleration in the knee joint are frequently used as initial values. In this study, we propose a method which can detect both the angle and angular acceleration in the knee joint at the same time by simple operations on the outputs of two accelerometers. The principle of knee‐joint motion detection, the evaluation of amplitude accuracy in the measured waveforms, and the evaluation of synchronization accuracy are successively described. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(7): 41–48, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11383