ABSTRACT
This study aimed to investigate changes in the H-reflex recruitment curve in compressive radiculopathy, specifically assessing differences between symptomatic and asymptomatic limbs in patients with unilateral S1 radiculopathy through derived parameters. A total of 24 volunteers (15 male and 9 female, aged between 22 and 60 years) with confirmed nerve root compression in the L5/S1 segment participated. Nerve root compression was verified through clinical MRI examination and attributed to disc protrusion, spinal canal stenosis, or isthmic spondylolisthesis of L5/S1. Analysis revealed no difference in M-wave threshold intensity between symptomatic and non-symptomatic limbs. However, the H-reflex exhibited a trend toward increased threshold intensity in the symptomatic limb. Notably, a significant decrease in the slope of the H-reflex was observed on the symptomatic side, and the maximal H-reflex amplitude proved to be markedly different between the two limbs. The Hmax/Mmax ratio demonstrated a significant decrease in the symptomatic limb, indicating reduced effectiveness of signal translation. In conclusion, our findings emphasize the importance of H-reflex parameters in evaluating altered recruitment curves, offering valuable insights for neurological examinations. The observed differences in maximal values of M-wave, H-reflex, and their ratio in affected and unaffected limbs can enhance the diagnostic process for lumbosacral unilateral radiculopathy and contribute to a standardized approach in clinical assessments.
Subject(s)
H-Reflex , Radiculopathy , Humans , H-Reflex/physiology , Female , Male , Radiculopathy/physiopathology , Radiculopathy/diagnosis , Adult , Middle Aged , Young Adult , ElectromyographyABSTRACT
Although recent studies in nonhuman primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brain stem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitudes of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs were unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.NEW & NOTEWORTHY Early and late portions of the response to transcranial magnetic stimulation (TMS) in a lower limb postural muscle are modulated independently by cortical suppression, late motor evoked potentials (MEPs) being facilitated during cortical inhibition. These results suggest a cortico-brain stem transmission pathway for late portions of the TMS-induced MEP.
Subject(s)
Evoked Potentials, Motor , Lower Extremity , Muscle, Skeletal , Transcranial Magnetic Stimulation , Male , Humans , Muscle, Skeletal/physiology , Evoked Potentials, Motor/physiology , Adult , Female , Lower Extremity/physiology , Motor Cortex/physiology , H-Reflex/physiology , Young Adult , Pyramidal Tracts/physiologyABSTRACT
Evaluating reciprocal inhibition of the thigh muscles is important to investigate the neural circuits of locomotor behaviors. However, measurements of reciprocal inhibition of thigh muscles using spinal reflex, such as H-reflex, have never been systematically established owing to methodological limitations. The present study aimed to clarify the existence of reciprocal inhibition in the thigh muscles using transcutaneous spinal cord stimulation (tSCS). Twenty able-bodied male individuals were enrolled. We evoked spinal reflex from the biceps femoris muscle (BF) by tSCS on the lumber posterior root. We examined whether the tSCS-evoked BF reflex was reciprocally inhibited by the following conditionings: (1) single-pulse electrical stimulation on the femoral nerve innervating the rectus femoris muscle (RF) at various inter-stimulus intervals in the resting condition; (2) voluntary contraction of the RF; and (3) vibration stimulus on the RF. The BF reflex was significantly inhibited when the conditioning electrical stimulation was delivered at 10 and 20 ms prior to tSCS, during voluntary contraction of the RF, and during vibration on the RF. These data suggested a piece of evidence of the existence of reciprocal inhibition from the RF to the BF muscle in humans and highlighted the utility of methods for evaluating reciprocal inhibition of the thigh muscles using tSCS.
Subject(s)
Spinal Cord Stimulation , Thigh , Humans , Male , Spinal Cord Stimulation/methods , Adult , Thigh/physiology , Thigh/innervation , Muscle, Skeletal/physiology , Muscle, Skeletal/innervation , Muscle Contraction/physiology , Transcutaneous Electric Nerve Stimulation/methods , Young Adult , H-Reflex/physiology , Femoral Nerve/physiology , Neural Inhibition/physiology , Quadriceps Muscle/physiology , Quadriceps Muscle/innervation , Hamstring Muscles/physiology , ElectromyographyABSTRACT
Considering the growing interest in clinical applications of neuromodulation, assessing effects of various modulatory approaches is increasingly important. Monosynaptic spinal reflexes undergo depression following repeated activation, offering a means to quantify neuromodulatory influences. Following spinal cord injury (SCI), changes in reflex modulation are associated with spasticity and impaired motor control. To assess disrupted reflex modulation, low-frequency depression (LFD) of Hoffman (H)-reflex excitability is examined, wherein the amplitudes of conditioned reflexes are compared to an unconditioned control reflex. Alternatively, some studies utilize paired-pulse depression (PPD) in place of the extended LFD train. While both protocols induce similar amounts of H-reflex depression in neurologically intact individuals, this may not be the case for persons with neuropathology. We compared the H-reflex depression elicited by PPD and by trains of 3-10 pulses to an 11-pulse LFD protocol in persons with incomplete SCI. The amount of depression produced by PPD was less than an 11-pulse train (mean difference = 0.137). When compared to the 11-pulse train, the 5-pulse train had a Pearson's correlation coefficient (R) of 0.905 and a coefficient of determination (R2) of 0.818. Therefore, a 5-pulse train for assessing LFD elicits modulation similar to the 11-pulse train and thus we recommend its use in lieu of longer trains.
Subject(s)
H-Reflex , Spinal Cord Injuries , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/complications , Humans , H-Reflex/physiology , Male , Adult , Female , Middle Aged , Electric StimulationABSTRACT
We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H-reflex increase. Up-conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p-p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H-reflex down-conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG-IR, and stronger p-p38-IR. More GABAergic terminals and weaker AnkG-IR correlated with greater H-reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H-reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H-reflex down-conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H-reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. KEY POINTS: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown. Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H-reflex up-conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down-conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p-p38 protein kinase. The associations between AIS plasticity and successful H-reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature. Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons.
Subject(s)
Axon Initial Segment , H-Reflex , Motor Neurons , Rats, Sprague-Dawley , Animals , Motor Neurons/physiology , Rats , Male , H-Reflex/physiology , Axon Initial Segment/physiology , Learning/physiology , Spinal Cord/physiology , Spinal Cord/cytology , Axons/physiology , Neuronal Plasticity/physiology , Conditioning, Operant/physiology , Ankyrins/metabolismABSTRACT
BACKGROUND: Acute lateral ankle sprains (ALAS) are associated with long-term impairments and instability tied to altered neural excitability. Arthrogenic muscle inhibition (AMI) has been observed in this population; however, relationships with injury-related impairments are unclear, potentially due to the resting, prone position in which AMI is typically measured. Assessing AMI during bipedal stance may provide a better understanding of this relationship. METHODS: AMI was assessed in 38 young adults (19 ALAS within 72 h of injury: 10 males, 21.4 ± 2.7 years; 19 healthy controls: 10 males, 21.9 ± 2.2 years; mean ± SD) using the Hoffmann reflex (H-reflex) during bipedal stance. Electrical stimulation was administered to identify the maximal H-reflex (Hmax) and maximal motor response (Mmax) from the soleus, fibularis longus, and tibialis anterior muscles. The primary outcome measure was the Hmax/Mmax ratio. Secondary outcomes included acute symptoms (pain and swelling), postural control during bipedal stance, and self-reported function. RESULTS: No significant group-by-limb interactions were observed for any muscle. However, a significant group main effect was observed in the soleus muscle (F(1,35)â¯=â¯6.82, pâ¯=â¯0.013), indicating significantly lower Hmax/Mmax ratios following ALAS (0.38 ± 0.20) compared to healthy controls (0.53 ± 0.16). Furthermore, lower Hmax/Mmax ratios in the soleus significantly correlated with acute symptoms and self-reported function but not with postural control. CONCLUSION: This study supports previous evidence of AMI in patients with ALAS, providing insight into neurophysiologic impacts of musculoskeletal injury. Our results suggest that assessing AMI in a standing position following acute injury may provide valuable insight into how AMI develops and guide potential therapeutic options to curb and offset the formation of joint instability.
Subject(s)
Ankle Injuries , H-Reflex , Muscle, Skeletal , Postural Balance , Humans , Male , Muscle, Skeletal/physiopathology , Young Adult , Postural Balance/physiology , Ankle Injuries/physiopathology , Female , H-Reflex/physiology , Sprains and Strains/physiopathology , Electromyography , Electric Stimulation , Case-Control Studies , AdultABSTRACT
OBJECTIVES: To investigate changes in the H-reflex in patients with monoradiculopathies involving L5 or S1 levels by stimulating the sciatic nerve and recording simultaneously from the tibialis anterior (TA), peroneus longus (PL), and soleus (S) muscles. METHODS: Patients with unilateral radicular back pain with L5 or S1 root compression on MRI, participated in this cross-sectional study. The H-reflex over the TA, PL, and S muscles was simultaneously recorded by sciatic nerve stimulation. The H-reflex latency was compared with that of the contralateral extremity. RESULTS: Fifty-eight patients (29 patients L5; 29 patients S1 radiculopathy) were included in the study. There were significant delays in the latency of the H-reflex over TA (30.95±2.31-29.21±1.4) and PL (31.05±2.85-29.02±1.99) muscles on the affected side in patients with L5 radiculopathy. However, the latency of the S H-reflex was similar on both sides. In contrast, in patients with S1 radiculopathy, there was a significant delay in the latency of soleus H reflex (32.76±3.45-29.9±3.19), while the significant delay was not detected in the TA and PL muscles. However, the cutoff values for the H-reflex latency of all muscles were not found to have clinical significance. CONCLUSIONS: The study presents that the H-reflex study, recorded from the TA, PL, and S muscles by sciatic nerve stimulation, is of interest but has minimal contribution to radiculopathy diagnosis in conventional electrodiagnostic tests.
Subject(s)
Radiculopathy , Humans , Radiculopathy/diagnosis , Spinal Nerve Roots , Cross-Sectional Studies , Muscle, Skeletal , H-Reflex/physiologyABSTRACT
The enigmatic benefits of acute limb ischemic preconditioning (IP) in enhancing muscle force and exercise performance have intrigued researchers. This study sought to unravel the underlying mechanisms, focusing on increased neural drive and the role of spinal excitability while excluding peripheral factors. Soleus Hoffmann (H)-reflex /M-wave recruitment curves and unpotentiated supramaximal responses were recorded before and after IP or a low-pressure control intervention. Subsequently, the twitch interpolation technique was applied during maximal voluntary contractions to assess conventional parameters of neural output. Following IP, there was an increase in both maximum normalized force and voluntary activation (VA) for the plantar flexor group, with negligible peripheral alterations. Greater benefits were observed in participants with lower VA levels. Despite greater H-reflex gains, soleus volitional (V)-wave and sEMG amplitudes remained unchanged. In conclusion, IP improves muscle force via enhanced neural drive to the muscles. This effect appears associated, at least in part, to reduced presynaptic inhibition and/or increased motoneuron excitability. Furthermore, the magnitude of the benefit is inversely proportional to the skeletal muscle's functional reserve, making it particularly noticeable in under-recruited muscles. These findings have implications for the strategic application of the IP procedure across diverse populations.
Subject(s)
Ischemic Preconditioning , Muscle, Skeletal , Male , Humans , Electromyography/methods , Muscle, Skeletal/physiology , Muscle Contraction/physiology , Motor Neurons/physiology , Isometric Contraction/physiology , H-Reflex/physiology , Electric StimulationABSTRACT
This study investigates the effects of varying loading conditions on excitability in neural pathways and gait dynamics. We focussed on evaluating the magnitude of the Hoffman reflex (H-reflex), a neurophysiological measure representing the capability to activate motor neurons and the timing and placement of the foot during walking. We hypothesized that weight manipulation would alter H-reflex magnitude, footfall and lower body kinematics. Twenty healthy participants were recruited and subjected to various weight-loading conditions. The H-reflex, evoked by stimulating the tibial nerve, was assessed from the dominant leg during walking. Gait was evaluated under five conditions: body weight, 20% and 40% additional body weight, and 20% and 40% reduced body weight (via a harness). Participants walked barefoot on a treadmill under each condition, and the timing of electrical stimulation was set during the stance phase shortly after the heel strike. Results show that different weight-loading conditions significantly impact the timing and placement of the foot and gait stability. Weight reduction led to a 25% decrease in double limb support time and an 11% narrowing of step width, while weight addition resulted in an increase of 9% in step width compared to body weight condition. Furthermore, swing time variability was higher for both the extreme weight conditions, while the H-reflex reduced to about 45% between the extreme conditions. Finally, the H-reflex showed significant main effects on variability of both stance and swing phases, indicating that muscle-motor excitability might serve as feedback for enhanced regulation of gait dynamics under challenging conditions.
Subject(s)
Gait , H-Reflex , Walking , Weight-Bearing , Humans , Gait/physiology , H-Reflex/physiology , Male , Adult , Female , Weight-Bearing/physiology , Biomechanical Phenomena/physiology , Young Adult , Walking/physiology , Electric Stimulation/methods , Muscle, Skeletal/physiology , Tibial Nerve/physiology , Electromyography , Foot/physiology , Adaptation, Physiological/physiology , Motor Neurons/physiology , Body Weight/physiologyABSTRACT
Operant conditioning of neural activation has been researched for decades in humans and animals. Many theories suggest two parallel learning processes, implicit and explicit. The degree to which feedback affects these processes individually remains to be fully understood and may contribute to a large percentage of non-learners. Our goal is to determine the explicit decision-making processes in response to feedback representing an operant conditioning environment. We developed a simulated operant conditioning environment based on a feedback model of spinal reflex excitability, one of the simplest forms of neural operant conditioning. We isolated the perception of the feedback signal from self-regulation of an explicit unskilled visuomotor task, enabling us to quantitatively examine feedback strategy. Our hypothesis was that feedback type, biological variability, and reward threshold affect operant conditioning performance and operant strategy. Healthy individuals (N = 41) were instructed to play a web application game using keyboard inputs to rotate a virtual knob representative of an operant strategy. The goal was to align the knob with a hidden target. Participants were asked to "down-condition" the amplitude of the virtual feedback signal, which was achieved by placing the knob as close as possible to the hidden target. We varied feedback type (knowledge of performance, knowledge of results), biological variability (low, high), and reward threshold (easy, moderate, difficult) in a factorial design. Parameters were extracted from real operant conditioning data. Our main outcomes were the feedback signal amplitude (performance) and the mean change in dial position (operant strategy). We observed that performance was modulated by variability, while operant strategy was modulated by feedback type. These results show complex relations between fundamental feedback parameters and provide the principles for optimizing neural operant conditioning for non-responders.
Subject(s)
Conditioning, Operant , Learning , Animals , Humans , Feedback , Conditioning, Operant/physiology , H-Reflex/physiology , MotivationABSTRACT
The soleus H-reflex modulation pattern was investigated during stepping following transspinal stimulation over the thoracolumbar region at 15, 30, and 50 Hz with 10 kHz carry-over frequency above and below the paresthesia threshold. The soleus H-reflex was elicited by posterior tibial nerve stimulation with a single 1 ms pulse at an intensity that the M-wave amplitudes ranged from 0 to 15% of the maximal M-wave evoked 80 ms after the test stimulus, and the soleus H-reflex was half the size of the maximal H-reflex evoked on the ascending portion of the recruitment curve. During treadmill walking, the soleus H-reflex was elicited every 2 or 3 steps, and stimuli were randomly dispersed across the step cycle which was divided in 16 equal bins. For each subject and condition, the soleus M-wave and H-reflex were normalized to the maximal M-wave. The soleus background electromyographic (EMG) activity was estimated as the linear envelope for 50 ms duration starting at 100 ms before posterior tibial nerve stimulation for each bin. The gain was determined as the slope of the relationship between the soleus H-reflex and the soleus background EMG activity. The soleus H-reflex phase-dependent amplitude modulation remained unaltered during transspinal stimulation, regardless frequency, or intensity. Similarly, the H-reflex slope and intercept remained the same for all transspinal stimulation conditions tested. Locomotor EMG activity was increased in knee extensor muscles during transspinal stimulation at 30 and 50 Hz throughout the step cycle while no effects were observed in flexor muscles. These findings suggest that transspinal stimulation above and below the paresthesia threshold at 15, 30, and 50 Hz does not block or impair spinal integration of proprioceptive inputs and increases activity of thigh muscles that affect both hip and knee joint movement. Transspinal stimulation may serve as a neurorecovery strategy to augment standing or walking ability in upper motoneuron lesions.
Subject(s)
Electromyography , H-Reflex , Muscle, Skeletal , Walking , Humans , H-Reflex/physiology , Walking/physiology , Male , Muscle, Skeletal/physiology , Adult , Young Adult , Female , Electric Stimulation/methods , Tibial Nerve/physiology , Spinal Cord/physiologyABSTRACT
To adequately evaluate the corticospinal and spinal plasticity in health and disease, it is essential to understand whether and to what extent the corticospinal and spinal responses fluctuate systematically across multiple measurements. Thus, in this study, we examined the session-to-session variability of corticospinal excitability for the ankle dorsiflexor tibialis anterior (TA) in people with and without incomplete spinal cord injury (SCI). In neurologically normal participants, the following measures were obtained across 4 days at the same time of day (N = 13) or 4 sessions over a 12-h period (N = 9, at 8:00, 12:00, 16:00, and 20:00): maximum voluntary contraction (MVC), maximum M-wave and H-reflex (Mmax and Hmax), motor evoked potential (MEP) amplitude, and silent period (SP) after MEP. In participants with chronic incomplete SCI (N = 17), the same measures were obtained across 4 days. We found no clear diurnal variation in the spinal and corticospinal excitability of the TA in individuals with no known neurological conditions, and no systematic changes in any experimental measures of spinal and corticospinal excitability across four measurement days in individuals with or without SCI. Overall, mean deviations across four sessions remained in a range of 5-13% for all measures in participants with or without SCI. The study shows the limited extent of non-systematic session-to-session variability in the TA corticospinal excitability in individuals with and without chronic incomplete SCI, supporting the utility of corticospinal and spinal excitability measures in mechanistic investigation of neuromodulation interventions. The information provided through this study may serve as the reference in evaluating corticospinal plasticity across multiple experimental sessions.
Subject(s)
Ankle , Spinal Cord Injuries , Humans , Ankle Joint , Muscle, Skeletal , Evoked Potentials, Motor/physiology , H-Reflex/physiology , Pyramidal Tracts , Electromyography , Transcranial Magnetic StimulationABSTRACT
INTRODUCTION/PURPOSE: Recently, the use of transcutaneous spinal cord stimulation (TSCS) has been proposed as a viable alternative to the H-reflex. The aim of the current study was to investigate to what extent the two modes of spinal cord excitability investigation would be similarly sensitive to the well-known vibration-induced depression. METHODS: Fourteen healthy participants (8 men and 6 women; age: 26.7 ± 4.8 years) were engaged in the study. The right soleus H-reflex and TSCS responses were recorded at baseline (PRE), during right Achilles tendon vibration (VIB) and following 20 min of vibration exposure (POST-VIB). Care was taken to match H-reflex and TSCS responses amplitude at PRE and to maintain effective stimulus intensities constant throughout time points. RESULTS: The statistical analysis showed a significant effect of time for the H-reflex, with VIB (13 ± 5% of maximal M-wave (Mmax) and POST-VIB (36 ± 4% of Mmax) values being lower than PRE-values (48 ± 6% of Mmax). Similarly, TSCS responses changed over time, VIB (9 ± 5% of Mmax) and POST-VIB (27 ± 5% of Mmax) values being lower than PRE-values (46 ± 6% of Mmax). Pearson correlation analyses revealed positive correlation between H-reflex and TSCS responses PRE-to-VIB changes, but not for PRE- to POST-VIB changes. CONCLUSION: While the sensitivity of TSCS seems to be similar to the gold standard H-reflex to highlight the vibratory paradox, both responses showed different sensitivity to the effects of prolonged vibration, suggesting slightly different pathways may actually contribute to evoked responses of both stimulation modalities.
Subject(s)
Achilles Tendon , H-Reflex , Muscle, Skeletal , Spinal Cord Stimulation , Vibration , Humans , Achilles Tendon/physiology , H-Reflex/physiology , Male , Female , Adult , Spinal Cord Stimulation/methods , Muscle, Skeletal/physiology , Spinal Cord/physiology , Transcutaneous Electric Nerve Stimulation/methodsABSTRACT
INTRODUCTION/AIMS: In amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre- and post-synaptic modulation of spinal motor neuron excitability by studying the H reflex, to understand spinal interneuron function in ALS. METHODS: We evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H'RI ) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H'Pre ) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H'Pos ). RESULTS: Fifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H'RI 0.35 vs. 0.11, p = .036; H'Pre 1.0 vs. 5.0, p = .001; H'Pos 0.0 vs. 2.5, p = .031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition. DISCUSSION: Spinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS.
Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Middle Aged , H-Reflex/physiology , Motor Neurons/physiology , Muscle, Skeletal , SpineABSTRACT
Spasticity is a hyperexcitability disorder that adversely impacts functional recovery and rehabilitative efforts after spinal cord injury (SCI). The loss of evoked rate-dependent depression (RDD) of the monosynaptic H-reflex is indicative of hyperreflexia, a physiological sign of spasticity. Given the intimate relationship between astrocytes and neurons, that is, the tripartite synapse, we hypothesized that astrocytes might have a significant role in post-injury hyperreflexia and plasticity of neighboring neuronal synaptic dendritic spines. Here, we investigated the effect of selective Rac1KO in astrocytes (i.e., adult male and female mice, transgenic cre-flox system) on SCI-induced spasticity. Three weeks after a mild contusion SCI, control Rac1wt animals displayed a loss of H-reflex RDD, that is, hyperreflexia. In contrast, transgenic animals with astrocytic Rac1KO demonstrated near-normal H-reflex RDD similar to pre-injury levels. Reduced hyperreflexia in astrocytic Rac1KO animals was accompanied by a loss of thin-shaped dendritic spine density on α-motor neurons in the ventral horn. In SCI-Rac1wt animals, as expected, we observed the development of dendritic spine dysgenesis on α-motor neurons associated with spasticity. As compared with WT animals, SCI animals with astrocytic Rac1KO expressed increased levels of the glial-specific glutamate transporter, glutamate transporter-1 in the ventral spinal cord, potentially enhancing glutamate clearance from the synaptic cleft and reducing hyperreflexia in astrocytic Rac1KO animals. Taken together, our findings show for the first time that Rac1 activity in astrocytes can contribute to hyperreflexia underlying spasticity following SCI. These results reveal an opportunity to target cell-specific molecular regulators of H-reflex excitability to manage spasticity after SCI.Significance Statement Spinal cord injury leads to stretch reflex hyperexcitability, which underlies the clinical symptom of spasticity. This study shows for the first time that astrocytic Rac1 contributes to the development of hyperreflexia after SCI. Specifically, astrocytic Rac1KO reduced SCI-related H-reflex hyperexcitability, decreased dendritic spine dysgenesis on α-motor neurons, and elevated the expression of the astrocytic glutamate transporter-1 (GLT-1). Overall, this study supports a distinct role for astrocytic Rac1 signaling within the spinal reflex circuit and the development of SCI-related spasticity.
Subject(s)
Reflex, Abnormal , Spinal Cord Injuries , Mice , Male , Female , Animals , Astrocytes/metabolism , Motor Neurons/physiology , Spinal Cord/metabolism , Animals, Genetically Modified , H-Reflex , Amino Acid Transport System X-AG/metabolismABSTRACT
PURPOSE: This study aims at comparing acute responses in spinal excitability, as measured by H-reflex, between older and young individuals, following a single session of NMES superimposed onto voluntary isometric contractions of the ankle plantar-flexor muscles (NMES+), with respect to passive NMES (pNMES) and voluntary isometric contractions only (ISO). METHODS: Thirty-two volunteers, 16 older (OLDER) and 16 young (YOUNG), were asked to sustain a constant force at 20% of maximal voluntary isometric contraction (MVIC) of the ankle plantar-flexor muscles in the dominant limb during each of the 3 conditions (NMES+ , pNMES and ISO). Fifteen repetitions of 6 s were performed, with a resting interval of 6 s between repetitions. Before and after each condition, soleus H-reflexes were elicited by percutaneous electrical stimulation of the posterior tibial nerve and H-reflex amplitudes recorded by surface EMG. RESULTS: In OLDER, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.203; pNMES: p = 0.542; NMES+: p = 0.431) compared to baseline. On the contrary, in YOUNG, H-reflex amplitudes significantly increased (p < 0.000) and decreased (p = 0.001) following NMES+ and pNMES, respectively, while there was no significant change in reflex responses following ISO (p = 0.772). CONCLUSION: The lack of change in H-reflex responses following either NMES+ or pNMES might reflect a reduced ability of older people in modulating spinal excitability after the conditions. Specifically, an age-related alteration in controlling mechanisms at presynaptic level was suggested.
Subject(s)
Muscle, Skeletal , Tibial Nerve , Humans , Aged , Adolescent , Muscle, Skeletal/physiology , Electromyography/methods , Tibial Nerve/physiology , Reflex/physiology , Electric Stimulation/methods , H-Reflex/physiology , Muscle Contraction/physiologyABSTRACT
INTRODUCTION/AIMS: Long latency reflexes (LLRs) are late responses in nerve conduction studies seen after peripheral nerve stimulation during submaximal muscle contraction. They follow a short latency reflex, also known as the H reflex, and are thought to involve transcortical pathways, providing a measure of proximal nerve and central conduction. For this reason, they have been evaluated in several central nervous system diseases, but reference values are not widely published and are mostly based on old studies with very small numbers of participants. Therefore, in this work we aim to provide comprehensive reference values for LLR testing. METHODS: LLRs were tested in a cohort of 100 healthy participants, testing the median nerve bilaterally. RESULTS: Mean latencies for short latency reflex (SLR), LLR1, LLR2, and LLR3 were 27.00, 38.50, 47.60, and 67.34 milliseconds, respectively. The allowable side-to-side difference was approximately 3 to 4 milliseconds. No significant sex-related differences were seen. Height correlated moderately with the SLR latency, but only weakly with LLR1, LLR2, and LLR3. DISCUSSION: This work provides normal LLR values for comparison with future studies in disease. The technique used may allow for improved evaluation of central nervous system or proximal peripheral nerve disorders.
Subject(s)
Median Nerve , Reflex , Humans , Adult , Median Nerve/physiology , Reaction Time/physiology , Muscle Contraction/physiology , Reference Values , H-Reflex , Electric StimulationABSTRACT
Excitatory feedback from muscle spindles, and inhibitory feedback from Golgi tendon organs and recurrent inhibitory circuits are widely distributed within the spinal cord to modulate activity between human lower limb muscles. Heteronymous feedback is most commonly studied in humans by stimulating peripheral nerves, but the unique effect of non-spindle heteronymous feedback is difficult to determine due to the lower threshold of excitatory spindle axons. A few studies suggest stimulation of the muscle belly preferentially elicits non-spindle heteronymous feedback. However, there remains a lack of consensus on the differential effect of nerve and muscle stimulation onto the H-reflex, and the relation of the heteronymous effects onto H-reflex compared to that onto ongoing EMG has not been determined. In this cross-sectional study, we compared excitatory and inhibitory effects from femoral nerve and quadriceps muscle belly stimulation onto soleus H-reflex size in 15 able-bodied participants and in a subset also compared heteronymous effects onto ongoing soleus EMG at 10% and 20% max. Femoral nerve stimulation elicited greater excitation of the H-reflex compared to quadriceps stimulation. The differential effect was also observed onto ongoing soleus EMG at 20% max but not 10%. Femoral nerve and quadriceps stimulation elicited similar inhibition of the soleus H-reflexes, and these results were better associated with soleus EMG at 20%. The results support surface quadriceps muscles stimulation as a method to preferentially study heteronymous inhibition at least in healthy adults. The primary benefit of using muscle stimulation is expected to be in persons with abnormal, prolonged heteronymous excitation. These data further suggest heteronymous feedback should be evaluated with H-reflex or onto ongoing EMG of at least 20% max to identify group differences or modulation of heteronymous feedback in response to treatment or task.
Subject(s)
H-Reflex , Quadriceps Muscle , Adult , Humans , H-Reflex/physiology , Femoral Nerve/physiology , Feedback , Cross-Sectional Studies , Muscle, Skeletal/physiology , Electric Stimulation , ElectromyographyABSTRACT
Diabetes Mellitus is a public health problem associated with complications such as neuropathy; however, it has been proposed that these may begin to develop during prediabetes and may also be present in persons with obesity. Diabetic peripheral neuropathy is the presence of signs and/or symptoms of peripheral nerve dysfunction in people living with diabetes, which increases the risk of developing complications and has a deleterious impact on quality of life. As part of the therapeutic protocol for diabetes, screening tests to identify peripheral neuropathy are suggested, however, there are no recommendations for people with prediabetes and obesity without symptoms such as pain, numbness, or paresthesias. Moreover, clinical screening tests that are usually used to recognize this alteration, such as tendon reflex, temperature sensation, and pressure and vibration perception, might be subjective as they depend on the evaluator's experience thus the incorrect application of these tests may not recognize the damage to small or large-nerve fibers. Recent evidence suggests that an objective study such as the impairment of the rate-dependent depression of the H-reflex could be used as a biomarker of spinal disinhibition and hence may provide more information on sensorimotor integration.