Simulated operant reflex conditioning environment reveals effects of feedback parameters.

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.

Ischemic preconditioning increases spinal excitability and voluntary activation during maximal plantar flexion contractions in men.

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.

The Diagnostic Role of Adding the Hoffman Reflex for L5 Radiculopathy in the Electrodiagnostic Laboratory: A Cross-sectional Study.

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.

Variability of corticospinal and spinal reflex excitability for the ankle dorsiflexor tibialis anterior across repeated measurements in people with and without incomplete spinal cord injury.

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.

Segmental motor neuron dysfunction in amyotrophic lateral sclerosis: Insights from H reflex paradigms.

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.

Conditional Astrocyte Rac1KO Attenuates Hyperreflexia after Spinal Cord Injury.

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.

Comparison of acute responses in spinal excitability between older and young people after neuromuscular electrical stimulation.

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.

Long latency reflexes of the median nerves in healthy adults.

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.

Differential effect of heteronymous feedback from femoral nerve and quadriceps muscle stimulation onto soleus H-reflex.

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.

Methods for automated delineation and assessment of EMG responses evoked by peripheral nerve stimulation in diagnostic and closed-loop therapeutic applications.

Objective.Surface electromyography measurements of the Hoffmann (H-) reflex are essential in a wide range of neuroscientific and clinical applications. One promising emerging therapeutic application is H-reflex operant conditioning, whereby a person is trained to modulate the H-reflex, with generalized beneficial effects on sensorimotor function in chronic neuromuscular disorders. Both traditional diagnostic and novel realtime therapeutic applications rely on accurate definitions of the H-reflex and M-wave temporal bounds, which currently depend on expert case-by-case judgment. The current study automates such judgments.Approach.Our novel wavelet-based algorithm automatically determines temporal extent and amplitude of the human soleus H-reflex and M-wave. In each of 20 participants, the algorithm was trained on data from a preliminary 3 or 4 min recruitment-curve measurement. Output was evaluated on parametric fits to subsequent sessions' recruitment curves (92 curves across all participants) and on the conditioning protocol's subsequent baseline trials (∼1200 per participant) performed nearHmax. Results were compared against the original temporal bounds estimated at the time, and against retrospective estimates made by an expert 6 years later.Main results.Automatic bounds agreed well with manual estimates: 95% lay within ±2.5 ms. The resulting H-reflex magnitude estimates showed excellent agreement (97.5% average across participants) between automatic and retrospective bounds regarding which trials would be considered successful for operant conditioning. Recruitment-curve parameters also agreed well between automatic and manual methods: 95% of the automatic estimates of the current required to elicitHmaxfell within±1.4%of the retrospective estimate; for the 'threshold' current that produced an M-wave 10% of maximum, this value was±3.5%.Significance.Such dependable automation of M-wave and H-reflex definition should make both established and emerging H-reflex protocols considerably less vulnerable to inter-personnel variability and human error, increasing translational potential.

Evidence of impaired H-reflex and H-reflex rate-dependent depression in diabetes, prediabetes and obesity: a mini-review.

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.

Acute effects of a single neurodynamic mobilization session on range of motion and H-reflex in asymptomatic young subjects: A controlled study.

Neurodynamic techniques have yielded good clinical results in the treatment of various pathologies. The objective of this study is to examine the short-term effects of neurodynamic techniques of the sciatic nerve on hip ROM (range of motion) and on the amplitude and latency of the soleus H-reflex and M-waves, in young asymptomatic subjects. In a double-blind controlled trial design, 60 young asymptomatic participants were randomly assigned into six groups with different levels of manipulation of the sciatic nerve. The passive straight leg raise test was used to evaluate the hip ROM amplitude. All evaluations were performed before, 1 min after, and 30 min after intervention. For each time-point, spinal and muscle excitability were also tested. ROM increased in all groups, but none of the treatment groups had superior effects than the group with no treatment. This means that ROM testing maneuvers increased ROM amplitude, with no add-on effect of the proposed neurodynamic techniques. Neurophysiological responses changed similarly in all groups, showing that the aftereffects were not intervention-specific. We observed a significant negative association between the change in limb temperature and the change in latencies of all potentials. ROM-testing procedures performed repeatedly increase ROM amplitude. This observation should be considered when evaluating the aftereffects of therapeutic interventions on ROM amplitude. None of the explored neurodynamic techniques produced acute aftereffects on hip ROM amplitude, spinal or muscle excitability different to the induced by the ROM testing maneuver.

Motor resonance to non-visible postural adaptation: A novel aspect of the mirror mechanism.

The activation of the Mirror Neuron System (MNS) has been described to reflect visible movements, but not postural, non-visible, adaptations that accompany the observed movements. Since any motor act is the result of a well-tailored dialogue between these two components, we decided to investigate whether a motor resonance to nonvisible postural adaptations could be detected. Possible changes in soleus corticospinal excitability were investigated by eliciting the H-reflex during the observation of three videos, corresponding to three distinct experimental conditions: 'Chest pass', 'Standing' and 'Sitting', and comparing its size with that measured during observation of a control videoclip (a landscape). In the observed experimental conditions, the Soleus muscle has different postural roles: a dynamic role in postural adaptations during the Chest pass; a static role while Standing still; no role while Sitting. The H-reflex amplitude was significantly enhanced in the 'Chest pass' condition compared to the 'Sitting' and 'Standing' conditions. No significant difference was found between 'Sitting' and 'Standing' conditions. The increased corticospinal excitability of the Soleus during the 'Chest pass' condition suggests that the mirror mechanisms produce a resonance to postural components of an observed action, although they may not be visible. This observation highlights the fact that mirror mechanisms echo non intentional movements as well and points to a novel possible role of mirror neurons in motor recovery.

Effects of active and sham tDCS on the soleus H-reflex during standing.

Weak transcranial direct current stimulation (tDCS) is known to affect corticospinal excitability and enhance motor skill acquisition, whereas its effects on spinal reflexes in actively contracting muscles are yet to be established. Thus, in this study, we examined the acute effects of Active and Sham tDCS on the soleus H-reflex during standing. In fourteen adults without known neurological conditions, the soleus H-reflex was repeatedly elicited at just above M-wave threshold throughout 30 min of Active (N = 7) or Sham (N = 7) 2-mA tDCS over the primary motor cortex in standing. The maximum H-reflex (Hmax) and M-wave (Mmax) were also measured before and immediately after 30 min of tDCS. The soleus H-reflex amplitudes became significantly larger (by 6%) ≈1 min into Active or Sham tDCS and gradually returned toward the pre-tDCS values, on average, within 15 min. With Active tDCS, the amplitude reduction from the initial increase appeared to occur more swiftly than with Sham tDCS. An acute temporary increase in the soleus H-reflex amplitude within the first minute of Active and Sham tDCS found in this study indicates a previously unreported effect of tDCS on the H-reflex excitability. The present study suggests that neurophysiological characterization of Sham tDCS effects is just as important as investigating Active tDCS effects in understanding and defining acute effects of tDCS on the excitability of spinal reflex pathways.

Modulation of H-reflex and V-wave responses during dynamic balance perturbations.

Motoneuron excitability is possible to measure using H-reflex and V-wave responses. However, it is not known how the motor control is organized, how the H-reflex and V-wave responses modulate and how repeatable these are during dynamic balance perturbations. To assess the repeatability, 16 participants (8 men, 8 women) went through two, identical measurement sessions with ~ 48 h intervals, where maximal isometric plantar flexion (IMVC) and dynamic balance perturbations in horizontal, anterior-posterior direction were performed. Soleus muscle (SOL) neural modulation during balance perturbations were measured at 40, 70, 100 and 130 ms after ankle movement by using both H-reflex and V-wave methods. V-wave, which depicts the magnitude of efferent motoneuronal output (Bergmann et al. in JAMA 8:e77705, 2013), was significantly enhanced as early as 70 ms after the ankle movement. Both the ratio of M-wave-normalized V-wave (0.022-0.076, p < 0.001) and H-reflex (0.386-0.523, p < 0.001) increased significantly at the latency of 70 ms compared to the latency of 40 ms and remained at these levels at latter latencies. In addition, M-wave normalized V-wave/H-reflex ratio increased from 0.056 to 0.179 (p < 0.001). The repeatability of V-wave demonstrated moderate-to-substantial repeatability (ICC = 0.774-0.912) whereas the H-reflex was more variable showing fair-to-substantial repeatability (ICC = 0.581-0.855). As a conclusion, V-wave was enhanced already at 70 ms after the perturbation, which may indicate that increased activation of motoneurons occurred due to changes in descending drive. Since this is a short time-period for voluntary activity, some other, potentially subcortical responses might be involved for V-wave increment rather than voluntary drive. Our results addressed the usability and repeatability of V-wave method during dynamic conditions, which can be utilized in future studies.

Differences in Trapezius Muscle H-Reflex between Asymptomatic Subjects and Symptomatic Shoulder Pain Subjects.

In chronic shoulder pain, adaptations in the nervous system such as in motoneuron excitability, could contribute to impairments in scapular muscles, perpetuation and recurrence of pain and reduced improvements during rehabilitation. The present cross-sectional study aims to compare trapezius neural excitability between symptomatic and asymptomatic subjects. In 12 participants with chronic shoulder pain (symptomatic group) and 12 without shoulder pain (asymptomatic group), the H reflex was evoked in all trapezius muscle parts, through C3/4 nerve stimulation, and the M-wave through accessory nerve stimulation. The current intensity to evoke the maximum H reflex, the latency and the maximum peak-to-peak amplitude of both the H reflex and M-wave, as well as the ratio between these two variables, were calculated. The percentage of responses was considered. Overall, M-waves were elicited in most participants, while the H reflex was elicited only in 58-75% or in 42-58% of the asymptomatic and symptomatic participants, respectively. A comparison between groups revealed that the symptomatic group presented a smaller maximum H reflex as a percentage of M-wave from upper trapezius and longer maximal H reflex latency from the lower trapezius (p < 0.05). Subjects with chronic shoulder pain present changes in trapezius H reflex parameters, highlighting the need to consider trapezius neuromuscular control in these individuals' rehabilitation.

Age-related changes in sensory and motor components of the Hoffmann-reflex pathway of the flexor carpi radialis.

Ageing is accompanied by numerous changes within the sensory and motor components of the muscle spindle pathway. To further document these age-related changes, this study compared the characteristics of the Hoffmann (H) reflex and M wave, evoked with several pulse durations, between young and old adults. The H-reflex and M-wave recruitment curves were recorded at rest in the flexor carpi radialis of 12 young (21-36 years) and 12 older adults (62-80 years). For each pulse duration (0.05, 0.2 and 1 ms), the maximal M-wave (MMAX ) and H-reflex (HMAX ) amplitude, the M-wave amplitude associated with HMAX (MHmax ) and the H-reflex amplitude for a stimulus intensity evoking an M-wave of 5% MMAX (HM5% ) were measured. The strength-duration time constant and response threshold were estimated from the charge/stimulus-duration relation for the H reflex and M wave. Results indicate that varying pulse duration mainly induces a similar effect on H-reflex and M-wave recruitment curves between young and older adults. Regardless of pulse duration, old adults had lesser HMAX (p = 0.029) and HM5% (p < 0.001) but greater MHmax (p < 0.001). The H-reflex and M-wave response thresholds were greater in old than young adults (p = 0.003), but the strength-duration time constant was lesser in old than young adults for the H reflex (p = 0.048) but not the M wave (p = 0.21). These results suggest greater age-related changes in the sensory than the motor component of the H-reflex pathway, which may be indicative of a greater loss of sensory than motor axons or alterations of synapses between Ia afferents and motor neurones.

Post-activation depression from primary afferent depolarization (PAD) produces extensor H-reflex suppression following flexor afferent conditioning.

Suppression of the extensor H-reflex by flexor afferent conditioning is thought to be produced by a long-lasting inhibition of extensor Ia afferent terminals via GABAA receptor-activated primary afferent depolarization (PAD). Given the recent finding that PAD does not produce presynaptic inhibition of Ia afferent terminals, we examined in 28 participants if H-reflex suppression is instead mediated by post-activation depression of the extensor Ia afferents triggered by PAD-evoked spikes and/or by a long-lasting inhibition of the extensor motoneurons. A brief conditioning vibration of the flexor tendon suppressed both the extensor soleus H-reflex and the tonic discharge of soleus motor units out to 150 ms following the vibration, suggesting that part of the H-reflex suppression during this period was mediated by postsynaptic inhibition of the extensor motoneurons. When activating the flexor afferents electrically to produce conditioning, the soleus H-reflex was also suppressed but only when a short-latency reflex was evoked in the soleus muscle by the conditioning input itself. In mice, a similar short-latency reflex was evoked when optogenetic or afferent activation of GABAergic (GAD2+ ) neurons produced a large enough PAD to evoke orthodromic spikes in the test Ia afferents, causing post-activation depression of subsequent monosynaptic EPSPs. The long duration of this post-activation depression and related H-reflex suppression (seconds) was similar to rate-dependent depression that is also due to post-activation depression. We conclude that extensor H-reflex inhibition by brief flexor afferent conditioning is produced by both post-activation depression of extensor Ia afferents and long-lasting inhibition of extensor motoneurons, rather than from PAD inhibiting Ia afferent terminals. KEY POINTS: Suppression of extensor H-reflexes by flexor afferent conditioning was thought to be mediated by GABAA receptor-mediated primary afferent depolarization (PAD) shunting action potentials in the Ia afferent terminal. In line with recent findings that PAD has a facilitatory role in Ia afferent conduction, we show here that when large enough, PAD can evoke orthodromic spikes that travel to the Ia afferent terminal to evoke EPSPs in the motoneuron. These PAD-evoked spikes also produce post-activation depression of Ia afferent terminals and may mediate the short- and long-lasting suppression of extensor H-reflexes in response to flexor afferent conditioning. Our findings highlight that we must re-examine how changes in the activation of GABAergic interneurons and PAD following nervous system injury or disease affects the regulation of Ia afferent transmission to spinal neurons and ultimately motor dysfunction in these disorders.

Modulation of corticospinal excitability related to the forearm muscle during robot-assisted stepping in humans.

In recent years, the neural control mechanisms of the arms and legs during human bipedal walking have been clarified. Rhythmic leg stepping leads to suppression of monosynaptic reflex excitability in forearm muscles. However, it is unknown whether and how corticospinal excitability of the forearm muscle is modulated during leg stepping. The purpose of the present study was to investigate the excitability of the corticospinal tract in the forearm muscle during passive and voluntary stepping. To compare the neural effects on corticospinal excitability to those on monosynaptic reflex excitability, the present study also assessed the excitability of the H-reflex in the forearm muscle during both types of stepping. A robotic gait orthosis was used to produce leg stepping movements similar to those of normal walking. Motor evoked potentials (MEPs) and H-reflexes were evoked in the flexor carpi radialis (FCR) muscle during passive and voluntary stepping. The results showed that FCR MEP amplitudes were significantly enhanced during the mid-stance and terminal-swing phases of voluntary stepping, while there was no significant difference between the phases during passive stepping. Conversely, the FCR H-reflex was suppressed during both voluntary and passive stepping, compared to the standing condition. The present results demonstrated that voluntary commands to leg muscles, combined with somatosensory inputs, may facilitate corticospinal excitability in the forearm muscle, and that somatosensory inputs during walking play a major role in monosynaptic reflex suppression in forearm muscle.