Postsynaptic potentials of soleus motor neurons produced by transspinal stimulation: a human single-motor unit study.

Transspinal (or transcutaneous spinal cord) stimulation is a noninvasive, cost-effective, easily applied method with great potential as a therapeutic modality for recovering somatic and nonsomatic functions in upper motor neuron disorders. However, how transspinal stimulation affects motor neuron depolarization is poorly understood, limiting the development of effective transspinal stimulation protocols for rehabilitation. In this study, we characterized the responses of soleus α motor neurons to single-pulse transspinal stimulation using single-motor unit (SMU) discharges as a proxy given the 1:1 discharge activation between the motor neuron and the motor unit. Peristimulus time histogram, peristimulus frequencygram, and surface electromyography (sEMG) were used to characterize the postsynaptic potentials of soleus motor neurons. Transspinal stimulation produced short-latency excitatory postsynaptic potentials (EPSPs) followed by two distinct phases of inhibitory postsynaptic potentials (IPSPs) in most soleus motor neurons and only IPSPs in others. Transspinal stimulation generated double discharges at short interspike intervals in a few motor units. The short-latency EPSPs were likely mediated by muscle spindle group Ia and II afferents, and the IPSPs via excitation of group Ib afferents and recurrent collaterals of motor neurons leading to activation of diverse spinal inhibitory interneuronal circuits. Further studies are warranted to understand better how transspinal stimulation affects depolarization of α motor neurons over multiple spinal segments. This knowledge will be seminal for developing effective transspinal stimulation protocols in upper motor neuron lesions.NEW & NOTEWORTHY Transspinal stimulation produces distinct actions on soleus motor neurons: an early short-latency excitation followed by two inhibitions or only inhibition and doublets. These results show how transspinal stimulation affects depolarization of soleus α motor neurons in healthy humans.

Demonstration of chewing-related areas in the brain via functional magnetic resonance imaging.

Purpose: To localize and identify chewing-related areas and their connections with other centres in the human brain using functional magnetic resonance imaging (fMRI). Material and methods: The paradigm of the present study was block designed. Spontaneous and controlled chewing with sugar-free gum was used as the main task in a 3-Tesla fMRI unit with a 32-channel birdcage coil. Our study popu-lation comprised 32 healthy volunteers. To determine possible intersections, we also put the rosary pulling (silent tell one's beads) movement in the fMRI protocol. The data analyses were performed with the Statistical Parametric Mapping (SPM) toolbox integrated into the Matlab platform. Results: The superomedial part of the right cerebellum was activated during either pulling rosary beads or spontaneous chewing. This region, however, was not activated during controlled chewing. We did not find statistically significant activation or connection related to the brain stem. Conclusion: We have confirmed that the cerebellum plays an important role in chewing. However, we could not find a definite central pattern generator (CPG) in the brain stem, which has been hypothesized to underlie spontaneous chewing.

An opinion on the 'delayed spikes' in human motoneurons.

This is a note challenging the claim by Kudina and Andreeva's recent publication in Experimental Brain Research. In that publication, Kudina and Andreeva (Exp Brain Res 239:719-730, 2021) put forward a new idea about discovering two spiking modes in human motoneurons. We suggest that what they have shown in their publication maybe is the motor unit firing indicating the end of a net synaptic potential. We reason this challenge from our previous publication in the same journal. In that publication, we have shown that the "second spiking mode" after the H-reflex was a return to the regular prestimulus discharge rate.

The reflex mechanism underlying the neuromuscular effects of whole-body vibration: Is it the tonic vibration reflex?

OBJECTIVES: Whole-body vibration (WBV) is applied to the sole of the foot, whereas local mechanical vibration (LMV) is applied directly to the muscle or tendon. The time required for the mechanical stimulus to reach the muscle belly is longer for WBV. Therefore, the WBV-induced muscular reflex (WBV-IMR) latency may be longer than the tonic vibration reflex (TVR) latency. The aim of this study was to determine whether the difference between WBV-IMR and TVR latencies is due to the distance between the vibration application point and the target muscle. METHODS: Eight volunteers participated in this study. The soleus reflex response was recorded during WBV, LMVs, and tendon tap. LMVs were applied to the Achilles tendon and sole of the foot. The latencies were calculated using the cumulative averaging technique. RESULTS: The latency (33.4±2.8 ms) of the soleus reflex induced by the local foot vibration was similar to the soleus TVR latency (30.9±3.2 ms) and T-reflex (32.0±2.4 ms) but significantly shorter than the latency of the soleus WBV-IMR (42.3±3.4 ms) (F(3,21)=27.46, p=0.0001, partial η2=0.797). CONCLUSIONS: The present study points out that the neuronal circuitries of TVR and WBV-IMR are different.

A new method to determine stretch reflex latency.

INTRODUCTION/AIMS: Motion artifact signals (MASs) created by the relative movement of intramuscular wire electrodes are an indicator of the mechanical stimulus arrival time to the muscle belly. This study proposes a method that uses wire electrodes as an intramuscular mechanosensor to determine the stretch reflex (SR) latency without lag time. METHODS: Gastrocnemius SR was induced by tendon tap, heel tap, and forefoot tap. The MASs recorded by intramuscular wire electrodes were extracted from background electromyographic activity using the spike-triggered averaging technique. Simultaneous recordings were obtained from multiple sites to validate the MAS technique. RESULTS: Using intramuscular wire electrodes, the MASs were successfully determined and extracted for all stimulus sites. In the records from the rectus femoris, MASs were also successfully extracted; thus, the reflex latency could be calculated. DISCUSSION: Wire electrodes can be used as an intramuscular mechanosensor to determine the mechanical stimulus arrival time to the muscle belly.

Estimating Exercise-Induced Changes in Human Neuronal Networks.

Although several methods have been used to estimate exercise-induced changes in human neuronal networks, there are growing doubts about the methodologies used. This review describes a single motor unit-based method that minimizes the errors inherent in classical methods. With this method, it is now possible to identify human neuronal networks' changes due to exercise.

Cross-training effect of chronic whole-body vibration exercise: a randomized controlled study.

Purpose: To determine whether unilateral leg whole-body vibration (WBV) strength training induces strength gain in the untrained contralateral leg muscle. The secondary aim was to determine the potential role of spinal neurological mechanisms regarding the effect of WBV exercise on contralateral strength training.Materials and Methods: Forty-two young adult healthy volunteers were randomized into two groups: WBV exercise and Sham control. An isometric semi-squat exercise during WBV was applied regularly through 20 sessions. WBV training was applied to the right leg in the WBV group and the left leg was isolated from vibration. Sham WBV was applied to the right leg of participants in the Control group. Pre- and post-training isokinetic torque and reflex latency of both quadricepses were evaluated.Results: The increase in the strength of right (vibrated) knee extensors was 9.4 ± 10.7% in the WBV group (p = .001) and was 1.2 ± 6.6% in the Control group (p = .724). The left (non-vibrated) extensorsvibrated) knee extensors w4 ± 8.4% in the WBV group (p = .038), whereas it decreased by 1.4 ± 7.0% in the Control (p = .294). The strength gains were significant between the two groups. WBV induced the reflex response of the quadriceps muscle in the vibrated ipsilateral leg and also in the non-vibrated contralateral leg, though with a definite delay. The WBV-induced muscle reflex (WBV-IMR) latency was 22.5 ± 7.7 ms for the vibrated leg and 39.3 ± 14.6 ms for the non-vibrated leg.Conclusions: Chronic WBV training has an effect of the cross-transfer of strength to contralateral homologous muscles. The WBV-induced muscular reflex may have a role in the mechanism of cross-transfer strength.

A stimulus rate that is not influenced by homosynaptic post-activation depression in chronic stroke.

PURPOSE: To determine a stimulus rate that is not influenced by homosynaptic post-activation depression for H-reflex studies in patients with chronic spasticity. MATERIALS AND METHODS: A cohort of 15 chronic stroke patients with soleus spasticity who received inpatient treatment at our rehabilitation centre participated in this study. The effect of stimulus frequency related depression on H-reflex size was tested using four different stimulus rates (0.1, 0.2, 0.3 and 1 Hz). The affected sides stibial nerve was stimulated by a bipolar electrode. The H-reflex was recorded from the affected sideed sidee sidehe affected smine stimulus frequency related depression of H-reflex size, amplitude of the first H-reflex response (H1) was used as control and amplitude of the second H-reflex response (H2) as test. RESULTS: H2 amplitude for frequency of 1 Hz, 0.3 Hz, 0.2 Hz and 0.1 Hz were 74.3, 84.1, 85.5 and 92.7% of H1, respectively. Depression of H2 amplitude was statistically significant for 1 Hz, 0.3 Hz and 0.2 Hz (p < 0.001, p = 0.002, p = 0.024, respectively). CONCLUSIONS: Higher frequency stimulation of Ia afferents than 0.1 Hz induced a stimulus frequency-related depression of H-reflex size in patients with chronic spasticity. The optimal stimulus rate for H-reflex was found to be 0.1 Hz.

Exploring the receptor origin of vibration-induced reflexes.

STUDY DESIGN: An experimental design. OBJECTIVES: The aim of this study was to determine the latencies of vibration-induced reflexes in individuals with and without spinal cord injury (SCI), and to compare these latencies to identify differences in reflex circuitries. SETTING: A tertiary rehabilitation center in Istanbul. METHODS: Seventeen individuals with chronic SCI (SCI group) and 23 participants without SCI (Control group) were included in this study. Latency of tonic vibration reflex (TVR) and whole-body vibration-induced muscular reflex (WBV-IMR) of the left soleus muscle was tested for estimating the reflex origins. The local tendon vibration was applied at six different vibration frequencies (50, 85, 140, 185, 235, and 265 Hz), each lasting for 15 s with 3-s rest intervals. The WBV was applied at six different vibration frequencies (35, 37, 39, 41, 43, and 45 Hz), each lasting for 15 s with 3-s rest intervals. RESULTS: Mean (SD) TVR latency was 39.7 (5.3) ms in the SCI group and 35.9 (2.7) ms in the Control group with a mean (95% CI) difference of -3.8 (-6.7 to -0.9) ms. Mean (SD) WBV-IMR latency was 45.8 (7.4) ms in the SCI group and 43.3 (3.0) ms in the Control group with a mean (95% CI) difference of -2.5 (-6.5 to 1.4) ms. There were significant differences between TVR latency and WBV-IMR latency in both the groups (mean (95% CI) difference; -6.2 (-9.3 to -3.0) ms, p = 0.0001 for the SCI group and -7.4 (-9.3 to -5.6) ms, p = 0.011 for Control group). CONCLUSIONS: The results suggest that the receptor of origin of TVR and WBV-IMR may be different.

Jendrassik maneuver effect on spinal and brainstem reflexes.

The effect of Jendrassik Maneuver (JM) has been extensively studied on monosynaptic reflexes in numerous muscles below the level at which the maneuver was performed. Here we hypothesize that the effect of JM could be observed also on other reflexes, indicating a widespread influence of performing a motor act such as the JM. We examined polysynaptic reflexes caudal (i.e., the withdrawal reflex of the lower extremities) and rostral (i.e., the blink reflex to supraorbital nerve stimulation) to the level of JM contraction. We have assessed soleus tendon (T) reflex; withdrawal reflex in tibialis anterior and soleus muscle; blink reflex (BR), blink reflex excitability recovery curve (BR-ER) and prepulse inhibition of the blink reflex. Our results showed that (1) T-reflex amplitude increased during JM and decreased just after and 15 min after JM; (2) no change in the withdrawal reflex; (3) R2 area of BR reduced significantly just after or 15 min after JM; (4) Prepulse inhibition in BR reduced significantly during JM; (5) no change in BR-ER. Our results indicate that JM leads to generalized effects on neural excitability at both caudal and rostral levels. Furthermore, JM has a selective effect on excitability of reflex circuitries.

Optimal location for eliciting the tibial H-reflex and motor response.

INTRODUCTION: Although there are numerous protocols to adjust the amplitude of the Hoffmann reflex (H-reflex) relative to the size of the direct motor response (M-response), the optimal stimulating location has not been described. We sought to determine the optimal positioning of the stimulating cathode when evoking the tibial nerve H-reflex and M-response. METHODS: A small cathode was placed on defined points in the popliteal fossa while an anode was fixed on the patella. The tibial nerve was stimulated electrically, and the response of the soleus muscle was recorded using intramuscular and surface electromyography. RESULTS: We found that more-lateral points along a line drawn across the popliteal fossa were the best locations to obtain only the M-response, whereas stimulating the midpoint was optimal for obtaining only the H-reflex. DISCUSSION: By using specified locations for electrical stimulation to evoke H-reflex and M-response, the functionality of the tibial nerve can be assessed. Muscle Nerve 58:828-833, 2018.

EEG-like signals can be synthesized from surface representations of single motor units of facial muscles.

Electrodes for recording electroencephalogram (EEG) are placed on or around cranial muscles; hence, their electrical activity may contaminate the EEG signal even at rest conditions. Due to its role in maintaining mandibular posture, tonic activity of temporalis muscle interferes with the EEG signal particularly at fronto-temporal locations at single motor unit (SMU) level. By obtaining surface representation of a motor unit, we can evaluate its interference in EEG and if we could sum surface representations of several tonically active motor units, we could estimate the overall myogenic contamination in EEG. Therefore, in this study, we followed re-composition (RC) approach and generated EEG-like artefact model using surface representations of single motor units (RC). Furthermore, we compared signal characteristics of RC signals with simultaneously recorded EEG signal at different locations in terms of power spectral density and coherence. First, we found that RC signal represented the power spectral distribution of an EMG signal. Second, RC signal reflected the discharge rate of a SMU giving the greatest surface representation amplitude and strongest interference appeared as distinguishable frequency peak on RC power spectra. Moreover, for strong interferences, RC also contaminated the EEG at F7 and other EEG electrodes. These findings are important to illustrate the susceptibility of EEG signal to myogenic artefacts even at rest and the research using EEG coherence comparisons should consider muscle activity while drawing conclusions about neuronal interactions and oscillations.

Posture modulates the sensitivity of the H-reflex.

The effect of body posture on the human soleus H-reflex via electrical stimulation of the tibial nerve at the popliteal fossa was studied. All parameters that may influence the reflex were controlled stringently. H-reflexes were elicited in three different body postures while keeping the level of background muscle activation to a minimum. The H-reflex curve relative to the M-wave curve did not change significantly in any of the body postures. However, the maximal H-reflex amplitude significantly increased in the prone position compared with the sitting (p = 0.02) and standing positions (p = 0.01). The background level of electrical activity of the soleus muscle did not significantly change during varying body postures. Together, these findings indicate that the effectiveness of the spindle primary afferent synapse on the soleus motor neuron pool changes significantly in prone position as compared to sitting and standing positions. Given that we have controlled the confounding factors excluding the head position relative to the gravity and the receptors that may be differentially activated at varying body postures such as the proprioceptors, it is concluded that the tonic activity from these receptors may presynaptically interfere with the effectiveness of the spindle primary afferent synapses on the soleus motor neurons.

The effects of a single session of spinal manipulation on strength and cortical drive in athletes.

PURPOSE: The primary purpose of this study was to investigate whether a single session of spinal manipulation (SM) increases strength and cortical drive in the lower limb (soleus muscle) of elite Taekwondo athletes. METHODS: Soleus-evoked V-waves, H-reflex and maximum voluntary contraction (MVC) of the plantar flexors were recorded from 11 elite Taekwondo athletes using a randomized controlled crossover design. Interventions were either SM or passive movement control. Outcomes were assessed at pre-intervention and at three post-intervention time periods (immediate post, post 30 min and post 60 min). A multifactorial repeated measures ANOVA was conducted to assess within and between group differences. Time and session were used as factors. A post hoc analysis was carried out, when an interactive effect was present. Significance was set at p ≤ 0.05. RESULTS: SM increased MVC force [F(3,30) = 5.95, p < 0.01], and V-waves [F(3,30) = 4.25, p = 0.01] over time compared to the control intervention. Between group differences were significant for all time periods (p < 0.05) except for the post60 force measurements (p = 0.07). CONCLUSION: A single session of SM increased muscle strength and corticospinal excitability to ankle plantar flexor muscles in elite Taekwondo athletes. The increased MVC force lasted for 30 min and the corticospinal excitability increase persisted for at least 60 min.

Reevaluation of reflex responses of the human masseter muscle to electrical lip stimulation.

We examined the reflex response of the human masseter muscle to electrical stimulation of the lip using both single motor unit and surface electromyogram based methods. Using the classical analysis methods, reflex response to mild electrical stimuli generated two distinct short-lasting inhibitions. This pattern may reflect the development of combinations of short- and long-latency inhibitory postsynaptic potentials as a result of the mildly painful electrical lip stimulation. However, this pattern appearing in the classical analysis methods may have developed as a consequence of earlier responses and may not be genuine. This study examined the genuineness of these responses using both the classical analysis methods and the discharge rate method to uncover the realistic postsynaptic potentials in human trigeminal motor nucleus. Using the discharge rate method, we found that the electrical lip stimulation only generated a long-lasting single or compound inhibitory response that is followed by late, long-lasting excitation. These findings have important implications on the redrawing of the neuronal pathways of the trigeminal nerve that are frequently used to judge neuromuscular disorders of the trigeminal region.NEW & NOTEWORTHY We examined the human masseter reflex response to electrical stimulation of lower lip to uncover realistic postsynaptic potentials in the trigeminal motor nucleus. We found that the stimulation generates a long-lasting single or compound inhibitory response that is followed by a late, long-lasting excitation. These findings have important implications on the redrawing of the neuronal pathways of the trigeminal nerve that are frequently used to judge neuromuscular disorders of the trigeminal region.

Estimating reflex responses in large populations of motor units by decomposition of the high-density surface electromyogram.

KEY POINTS: Reflex responses of single motor units have been used for the study of spinal circuitries but the methods employed are invasive and limited to the assessment of a relatively small number of motor units. We propose a new approach to investigate reflexes on individual motor units based on high-density surface electromyography (HDsEMG) decomposition. The decomposition of HDsEMG has been previously validated in voluntary isometric contractions but never during reflex activities. The use of HDsEMG decomposition for reflex studies at the individual motor unit level, during constant force contractions, with excitatory and inhibitory stimuli, was validated here by the comparison of results with concurrently recorded intramuscular EMG signals. The validation results showed that HDsEMG decomposition allows an accurate quantification of reflex responses for a large number of individual motor units non-invasively, for both excitatory and inhibitory stimuli. ABSTRACT: We propose and validate a non-invasive method that enables accurate detection of the discharge times of a relatively large number of motor units during excitatory and inhibitory reflex stimulations. High-density surface electromyography (HDsEMG) and intramuscular EMG (iEMG) were recorded from the tibialis anterior muscle during ankle dorsiflexions performed at 5%, 10% and 20% of the maximum voluntary contraction (MVC) force, in nine healthy subjects. The tibial nerve (inhibitory reflex) and the peroneal nerve (excitatory reflex) were stimulated with constant current stimuli. In total, 416 motor units were identified from the automatic decomposition of the HDsEMG. The iEMG was decomposed using a state-of-the-art decomposition tool and provided 84 motor units (average of two recording sites). The reflex responses of the detected motor units were analysed using the peri-stimulus time histogram (PSTH) and the peri-stimulus frequencygram (PSF). The reflex responses of the common motor units identified concurrently from the HDsEMG and the iEMG signals showed an average disagreement (the difference between number of observed spikes in each bin relative to the mean) of 8.2 ± 2.2% (5% MVC), 6.8 ± 1.0% (10% MVC) and 7.5 ± 2.2% (20% MVC), for reflex inhibition, and 6.5 ± 4.1%, 12.0 ± 1.8% and 13.9 ± 2.4%, for reflex excitation. There was no significant difference between the characteristics of the reflex responses, such as latency, amplitude and duration, for the motor units identified by both techniques. Finally, reflex responses could be identified at higher force (4 of the 9 subjects performed contraction up to 50% MVC) using HDsEMG but not iEMG, because of the difficulty in decomposing the iEMG at high forces. In conclusion, single motor unit reflex responses can be estimated accurately and non-invasively in relatively large populations of motor units using HDsEMG. This non-invasive approach may enable a more thorough investigation of the synaptic input distribution on active motor units at various force levels.

Changes in H-reflex and V-waves following spinal manipulation.

This study investigates whether spinal manipulation leads to neural plastic changes involving cortical drive and the H-reflex pathway. Soleus evoked V-wave, H-reflex, and M-wave recruitment curves and maximum voluntary contraction (MVC) in surface electromyography (SEMG) signals of the plantar flexors were recorded from ten subjects before and after manipulation or control intervention. Dependent measures were compared with 2-way ANOVA and Tukey's HSD as post hoc test, p was set at 0.05. Spinal manipulation resulted in increased MVC (measured with SEMG) by 59.5 ± 103.4 % (p = 0.03) and force by 16.05 ± 6.16 4 % (p = 0.0002), increased V/M max ratio by 44.97 ± 36.02 % (p = 0.006), and reduced H-reflex threshold (p = 0.018). Following the control intervention, there was a decrease in MVC (measured with SEMG) by 13.31 ± 7.27 % (p = 0.001) and force by 11.35 ± 9.99 % (p = 0.030), decreased V/M max ratio (23.45 ± 17.65 %; p = 0.03) and a decrease in the median frequency of the power spectrum (p = 0.04) of the SEMG during MVC. The H-reflex pathway is involved in the neural plastic changes that occur following spinal manipulation. The improvements in MVC following spinal manipulation are likely attributed to increased descending drive and/or modulation in afferents. Spinal manipulation appears to prevent fatigue developed during maximal contractions. Spinal manipulation appears to alter the net excitability of the low-threshold motor units, increase cortical drive, and prevent fatigue.

Human stretch reflex pathways reexamined.

Reflex responses of tibialis anterior motor units to stretch stimuli were investigated in human subjects. Three types of stretch stimuli were applied (tap-like, ramp-and-hold, and half-sine stretch). Stimulus-induced responses in single motor units were analyzed using the classical technique, which involved building average surface electromyogram (SEMG) and peristimulus time histograms (PSTH) from the discharge times of motor units and peristimulus frequencygrams (PSF) from the instantaneous discharge rates of single motor units. With the use of SEMG and PSTH, the tap-like stretch stimulus induced five separate reflex responses, on average. With the same single motor unit data, the PSF technique indicated that the tap stimulus induced only three reflex responses. Similar to the finding using the tap-like stretch stimuli, ramp-and-hold stimuli induced several peaks and troughs in the SEMG and PSTH. The PSF analyses displayed genuine increases in discharge rates underlying the peaks but not underlying the troughs. Half-sine stretch stimuli induced a long-lasting excitation followed by a long-lasting silent period in SEMG and PSTH. The increase in the discharge rate, however, lasted for the entire duration of the stimulus and continued during the silent period. The results are discussed in the light of the fact that the discharge rate of a motoneuron has a strong positive linear association with the effective synaptic current it receives and hence represents changes in the membrane potential more directly and accurately than the other indirect measures. This study suggests that the neuronal pathway of the human stretch reflex does not include inhibitory pathways.

Mimicking human neuronal pathways in silico: an emergent model on the effective connectivity.

We present a novel computational model that detects temporal configurations of a given human neuronal pathway and constructs its artificial replication. This poses a great challenge since direct recordings from individual neurons are impossible in the human central nervous system and therefore the underlying neuronal pathway has to be considered as a black box. For tackling this challenge, we used a branch of complex systems modeling called artificial self-organization in which large sets of software entities interacting locally give rise to bottom-up collective behaviors. The result is an emergent model where each software entity represents an integrate-and-fire neuron. We then applied the model to the reflex responses of single motor units obtained from conscious human subjects. Experimental results show that the model recovers functionality of real human neuronal pathways by comparing it to appropriate surrogate data. What makes the model promising is the fact that, to the best of our knowledge, it is the first realistic model to self-wire an artificial neuronal network by efficiently combining neuroscience with artificial self-organization. Although there is no evidence yet of the model's connectivity mapping onto the human connectivity, we anticipate this model will help neuroscientists to learn much more about human neuronal networks, and could also be used for predicting hypotheses to lead future experiments.

Single motor unit estimation of the cutaneous silent period in ALS.

OBJECTIVE: Recent evidence indicated that amyotrophic lateral sclerosis (ALS) also impairs spinal circuits, including those mediating cutaneous silent period (CSP). However, most studies utilised surface electromyography (sEMG), which needs more resolution to pinpoint changes at the single motoneuron level. We aimed to investigate CSP properties using single motor unit discharges in ALS. METHODS: In mild and severe ALS patients and controls, CSP was recorded in the first dorsal interosseus and analysed using the discharge rate method, which accurately shows the inhibitory postsynaptic potentials (IPSPs) profile. RESULTS: Our findings confirmed that the CSP latency was prolonged only in severe ALS patients. Moreover, the CSP duration was similar in each group, but late-stage ALS patients tend to have a longer CSP duration. The discharge rate method revealed a significantly longer duration (up to 150 ms) than the duration detected using sEMG. Strikingly, the motoneuron discharge rate - IPSP duration inverse relationship is lost in ALS patients, indicating a possible impairment in the motoneuron integrative properties. CONCLUSIONS: Our data support previous findings of prolonged latency, presented input-output modifications of motoneurons, and revealed the entire course of the CSP, representing a much stronger inhibitory event than previously thought. SIGNIFICANCE: Motoneuron integrative property modification assessed by CSP could be a new biomarker for ALS.