The firing rate of motor units in neuromuscular disorders

Summary The firing frequency and interval variability of motor units was studied in healthy controls and in patients suffering from peripheral neuromuscular disorders. In patients with myopathic disorders, the motor unit reached a higher firing frequency than in the controls during a slight muscle contraction although interval variability did not differ significantly from controls. In neurogenic lesions the firing rate also reached a higher level than in controls; in addition the interval variability was significantly increased. The firing characteristics of motor units may prove to be a valuable aid in the differential diagnosis of neuromuscular diseases.

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Zusammenfassung Die Entladungsfrequenz und die Variationen zwischen den Intervallen motorischer Einheiten wurden sowohl bei Patienten, die an Störungen peripherer Neuromuskulatur leiden, als auch bei Normalfällen im Vergleich untersucht. Während einer leichten Muskelkontraktion wiesen die an myopathischen Störungen leidenden Patienten, verglichen mit den Normalfällen, eine höhere Entladungsfrequenz motorischer Einheiten auf, trotz der unbedeutenden Unterschiede in Intervallvariationen zwischen den Untersuchungsgruppen. Eine größere Steigerung der Entladungsrate wurde auch bei neurogenen Läsionen festgestellt, in diesem Zusammenhang hatten auch die Abweichungen zwischen den Intervallen beträchtlich zugenommen. Die Entladungscharakteristika motorischer Einheiten können einen wertvollen Beitrag zur Differentialdiagnostik bei neuromuskulären Störungen liefern.

     

Motor unit recruitment and firing rates interaction in the control of human muscles

Muscle contractions are modulated by the number of motor units recruited and their respective firing rates. The work described in this report documents an interplay between recruitment and firing rates of motor units. The recruitment of a new motor unit appears to have a disfacilitatory influence on the firing rates of previously activated motor units. It is speculated that this effect is likely to be mediated, at least partially, via the stretch reflex loop and possibly by the recurrent inhibition of the Renshaw circuit. Such a mechanism would be functionally useful in providing smooth control of muscle output via peripheral circuitry (consisting of proprioceptive reflexes and recurrent inhibition), thus lessening the amount of detailed supervision of the alpha-motoneuron pool required by the central nervous system.     

Motor unit firing in amyotrophic lateral sclerosis and other upper and lower motor neurone disorders

Objective

Motor unit recruitment order and firing rate was investigated in healthy subjects, and in small numbers of patients 50 years ago. We aimed to investigate firing rate in different disorders, testing the same target muscle with normal strength, to evaluate possible application in diagnosing upper motor neuron (UMN) lesion.

Methods

We studied motor unit firing in the tibialis anterior muscle in six groups of subjects; normal subjects (n = 45), patients with amyotrophic lateral sclerosis (ALS) (n = 36), primary lateral sclerosis (PLS) (n = 21), progressive muscular atrophy (PMA) (n = 14), various upper motor neurone lesions (n = 16) and polyneuropathy (n = 42). In all these subjects the tibialis anterior muscle was of normal strength. Motor units were recruited during slight contraction in order to study 2–5 motor units at each recording site, using a standard concentric needle electrode, so that 20–22 motor units were recorded in each muscle. We analysed the coefficient of variation (CV) for amplitude, area, duration and firing rate in these motor units, and the correlation between motor unit potential size and recruitment order.

Results

The mean MU firing rate in this task was similar in each group. No recruitment order was disclosed within the limits of the study task. The CV of firing rate was decreased in UMN and PLS groups. ALS patients with marked spasticity showed a lower CV of motor unit firing rate. The CV of amplitude, area and duration was similar between groups.

Conclusions

These results in tibialis anterior indicate that physiological modulation of lower motor neuron (LMN) firing rate is decreased in patients with lower limb spasticity. The variability of MU discharges tends to be greater in diseases affecting the LMN.

Significance

These results suggest that, notwithstanding the simplicity of the task we have used, the physiological variability of motor unit firing may be a useful variable in assessing UMN involvement in motor system disorders.     

Motor unit number estimation in neuromuscular disease

Motor unit number estimation (MUNE) is an electrophysiological method designed to quantify motor unit loss in target muscles of interest. Most of the techniques are noninvasive and are therefore well suited for longitudinal monitoring. In this brief review, we describe the more commonly used techniques and their applications in amyotrophic lateral sclerosis, poliomyelitis, spinal muscular atrophy and hereditary sensorimotor neuropathies. Findings in some of these studies offer important pathophysiological insights. Since conventional electrophysiologic methods are not sensible measures of motor neuronal loss, MUNE could play a potentially important role in the diagnosis, monitoring of disease progression and response to treatment in neuromuscular diseases in which motor unit loss is a major feature.     

Approach to neuromuscular disorders in the intensive care unit

Neuromuscular disorders increasingly are recognized as a complication in patients in the intensive care unit (ICU) and represent a common cause of prolonged ventilator dependency. The distinct syndromes of critical illness myopathy, prolonged neuromuscular blockade, and critical illness polyneuropathy (CIP) may arise as a consequence of sepsis, multi-organ failure, and exposure to various medications—notably, intravenous corticosteroids and neuromuscular blocking agents—but the pathophysiology of these disorders remains poorly understood. More than one syndrome may occur simultaneously, and the distinctions may be difficult in a particular patient, but a specific diagnosis usually can be established after careful clinical, electrodiagnostic, and, when necessary, histological evaluation. For example, asthmatics requiring treatment with corticosteroids and neuromuscular blocking agents may develop an acute myopathy characterized by generalized weakness, preserved eye movements, elevated creatine kinase levels, and myopathic motor units on electromyography (EMG). Muscle biopsy demonstrates distinctive features of thick (myosin) filament loss on ultrastructural studies. Conversely, those with a prolonged ICU course that is complicated by episodes of sepsis with failure to wean from the ventilator, distal or generalized flaccid limb weakness, and areflexia probably have CIP. EMG in these patients demonstrates reduced or absent motor and sensory potentials with neurogenic motor units. Prolonged neuromuscular blockade most commonly occurs in patients with renal failure who have received prolonged infusions of neuromuscular blockers. There is severe flaccid, areflexic paralysis with normal sensation, facial weakness, and ophthalmoparesis that persists for days or weeks after the neuromuscular blockers have been discontinued. Repetitive nerve stimulation shows a decrement of the compound muscle action potential and, in most cases, establishes a disorder of neuromuscular transmission. With the recent epidemic of West Nile virus infection, a clinical syndrome of acute flaccid paralysis with several features indistinguishable from poliomyelitis has emerged. This article critically examines the clinical, electrophysiological, and pathological features of these and other acute neuromuscular syndromes that arise in the context of ICU care and summarizes the current understanding of the pathophysiology and treatment of these disorders.     

The motor unit firing rate and the power spectrum of EMG in humans

The EMG power spectrum is influenced by many factors such as the conduction velocity of the muscle fiber, the action potential of the motor unit, the number of motor units firing near the electrode, and the recording conditions. Model studies of the relation between motor unit firing rate and power spectrum of EMG have produced conflicting results. To examine this relation in vivo the brachial biceps muscle was examined in 14 controls at a force of 10% of maximum. The motor unit firing intervals were obtained from 164 motor units, sampled with a single fiber electrode. The EMG was sampled at 10 sites in each muscle with a concentric electrode and the power spectrum was obtained using fast Fourier transformation. The mean power frequency of the interference pattern as well as the relative power at 1400 Hz both decreased with increasing motor unit firing intervals between subjects. The study thus indicates that the amount of high frequencies in the power spectrum is greater in a subject with a high firing rate of the motor units than in a subject with a low firing rate.     

Interleaved neuromuscular electrical stimulation: Motor unit recruitment overlap

Introduction: In this study, we quantified the “overlap” between motor units recruited by single pulses of neuromuscular electrical stimulation (NMES) delivered over the tibialis anterior muscle (mNMES) and the common peroneal nerve (nNMES). We then quantified the torque produced when pulses were alternated between the mNMES and nNMES sites at 40 Hz (“interleaved” NMES; iNMES). Methods: Overlap was assessed by comparing torque produced by twitches evoked by mNMES, nNMES, and both delivered together, over a range of stimulus intensities. Trains of iNMES were delivered at the intensity that produced the lowest overlap. Results: Overlap was lowest (5%) when twitches evoked by both mNMES and nNMES produced 10% peak twitch torque. iNMES delivered at this intensity generated 25% of maximal voluntary dorsiflexion torque (11 Nm). Discussion: Low intensity iNMES leads to low overlap and produces torque that is functionally relevant to evoke dorsiflexion during walking. Muscle Nerve 55 : 490–499, 2017     

Shape irregularity of motor unit potentials in some neuromuscular disorders

The aim of this study was to test whether analysis of the irregularity of the motor unit potential waveform may supplement conventional evaluation. We have found that the irregularity is not a characteristic feature of potentials either in neurogenic disorders or in myopathy. We have found, however, that within myo- and neuropathic disorders, the irregularities differ between slow (such as Becker muscle dystrophy and chronic spinal muscle atrophy) and fast progressing processes (such as amyotrophic lateral sclerosis and Duchenne muscle dystrophy). These differences depend on the different number of phases and turns contributing to wave formation. In slowly progressing processes, very irregular potentials are more often polyphasic, whereas in acute processes they may be polyturn or polyphasic. The results suggest that it is the irregularity of the potential that provides new information, not available so far, on the activity of the pathological process. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1181–1187, 1998.     

Motor unit number estimation and neuromuscular fidelity in 3 stages of sarcopenia

Introduction: Loss of motor units (MUs) and alterations in MU properties are major factors in development of sarcopenia. The purpose of this study was to compare MU properties among 3 groups categorized as either pre‐sarcopenic (n = 7), sarcopenic (n = 7), or severely sarcopenic (n = 5), all with similarly aged subjects (75–82 years). Methods: Using decomposition‐enhanced quantitative electromyography, MU number estimates and neuromuscular stability measures of near‐fiber (NF) jitter and jiggle were derived in addition to contractile properties of ankle dorsiflexors. Results: MU number estimates were similar across groups; however, maximal voluntary strength in the severe sarcopenia group was 27% and 37% less than the sarcopenic and pre‐sarcopenic groups, respectively. Moreover, NF jiggle was 31% greater in the severe group compared with pre‐sarcopenia, NF jitter was 43% greater in the severe group compared with the pre‐sarcopenic group. Conclusion: Unlike MU number estimates, strength and MU stability differed across groups and related to degree of sarcopenia. Muscle Nerve 55: 676–684, 2017     

Peak-ratio interference pattern analysis in the detection of neuromuscular disorders

Peak-ratio interference pattern analysis (peak-ratio method) is said to have a high sensitivity and to be independent of sex and age. This study was carried out to prove or disprove these findings. The peak-ratio method and qualitative motor unit action potential (MUAP) analysis were applied to the right brachial biceps and anterior tibial muscles of 44 healthy subjects, aged 23–87 years, 25 neuropathy patients, aged 21–83 years, and 29 myopathy patients, aged 19–70 years. Peak-ratio parameters were independent of sex and age. They tended to be lower in the anterior tibial muscle than in the brachial biceps muscle. Neuropathy patients typically showed decreased peak-ratio, short time intervals and increased amplitude/turn. Myopathy patients typically showed increased peak-ratio, turns/s and short time intervals. The sensitivity of the peak-ratio method was 72% for neuropathy patients and 59% for myopathy patients. The sensitivity of the peak-ratio method was similar to that of the MUAP analysis in neuropathy patients and higher than that of the MUAP analysis in myopathy patients. The specificity of the peak-ratio method was 80%. The peak-ratio method proved to be a valuable, supplementary electromyographic tool for the detection of neuromuscular disorders.     

Evaluation of motor unit potential wavelet analysis in the electrodiagnosis of neuromuscular disorders

Introduction: Electrophysiological studies of human motor units can use various electromyographic techniques. Together with the development of new techniques for analysis and processing of bioelectric signals, motor unit action potential (MUAP) wavelet analysis represents an important change in the development of electromyographic techniques. Methods: The proposed approach involves isolating single MUAPs, computing their scalograms, taking the maximum values of the scalograms in 5 selected scales, and averaging across MUAPs to give a single five‐dimensional feature vector per muscle. After Support Vector Machine analysis, the feature vector is reduced to a single decision parameter that allows the subject to be assigned to 1 of 3 groups: myogenic, healthy, or neurogenic. The software is available as freeware. Results: MUAP wavelet analysis yielded consistent results for the diagnostic index and muscle classification, with only 7 incorrect classifications out of a total of 1,015 samples. Conclusions: This proposed approach provides a sensitive and reliable method for evaluating and characterizing MUAPs. Muscle Nerve 46: 63–69, 2012     

Motor unit firing intervals and other parameters of electrical activity in normal and pathological muscle

The analysis of the firing intervals of motor units has been suggested as a diagnostic tool in patients with neuromuscular disorders. Part of the increase in number of turns seen in patients with myopathy could be secondary to the decrease in motor unit firing intervals at threshold force of the motor units, as noted in previous studies. In the brachial biceps muscle we have studied the firing intervals of 164 motor units in 14 controls, 140 motor units in 13 patients with myopathy and 86 motor units in 8 patients with neurogenic disorders, and related the findings to those of the turns analysis and the analysis of properties of individual motor unit potentials. To ensure comparable conditions we have examined motor unit firing intervals and turns at a force of 10% of maximum. The average of motor unit firing intervals and of interval variability was the same in controls and in patients, and the diagnostic yield of the motor unit firing intervals analysis was none. Although the number of turns increased with decreasing motor unit firing intervals, this relation was physiological rather than pathophysiological. In patients with neurogenic disorders, interval variability indicated unstable firing in severely affected muscles.     

Instability of motor unit firing rates during prolonged isometric contractions in human masseter

The firing patterns of up to 4 concurrently active masseter motor units were studied with intramuscular electrodes during a continuous isometric contraction of 15 min duration, in which the subject maintained the mean firing rate of one selected unit at 10 Hz. With this paradigm the net excitation (i.e. mean firing rate) of one unit in the muscle was controlled. This served as the reference for the functional state of other active units during the prolonged contraction. With the mean firing rate of one unit in the muscle fixed, 58% of other active units showed a slow, statistically-significant change in mean firing rate over the 15 min. The initial firing rate of the units did not influence the change in rate. The original firing rate hierarchy, which in short-term contractions reflects the recruitment order, was altered during the prolonged contraction. The explanation for these differential changes in motoneuron net excitation is not clear; they could be intrinsic to the motoneurons or perhaps mediated by reflex pathways. The selective facilitation or suppression of some motor units with continuous activation means that the original size-structured combination of motor units can be modified during a prolonged contraction.     

The relationship of motor unit size, firing rate and force.

OBJECTIVE: Using a clinical electromyographic (EMG) protocol, motor units were sampled from the quadriceps femoris during isometric contractions at fixed force levels to examine how average motor unit size and firing rate relate to force generation. METHODS: Mean firing rates (mFRs) and sizes (mean surface-detected motor unit action potential (mS-MUAP) area) of samples of active motor units were assessed at various force levels in 79 subjects. RESULTS: MS-MUAP size increased linearly with increased force generation, while mFR remained relatively constant up to 30% of a maximal force and increased appreciably only at higher force levels. A relationship was found between muscle force and mS-MUAP area (r2 = 0.67), mFR (r2 = 0.38), and the product of mS-MUAP area and mFR (mS-MUAP x mFR) (r2 = 0.70). CONCLUSIONS: The results support the hypothesis that motor units are recruited in an orderly manner during forceful contractions, and that in large muscles only at higher levels of contraction ( > 30% MVC) do mFRs increase appreciably. MS-MUAP and mFR can be assessed using clinical EMG techniques and they may provide a physiological basis for analyzing the role of motor units during muscle force generation.     

Motor unit synchronous firing as revealed by determinism of surface myoelectric signal

Information on motor strategies can be extracted from the surface electromyogram (EMG) by non-linear methods. The percentage of determinism (%DET) obtained from recurrence quantification analysis (RQA) may be a sensitive variable to detect synchronous motor unit behaviour. The purpose of the present study was to validate this methodology by comparing it with an established technique estimating the degree of synchronization of pairs of voluntary activated motor units from the correlation of their firing in the time-domain. Single motor unit activity was recorded in extensor carpi radialis (ECR) muscle by pairs of tungsten microelectrodes inserted into the muscle belly. Cross-correlation analysis was performed in order to determine synchronization peak area by computing synchronous impulse probability. Surface EMG activity was recorded in parallel by electrodes placed over the skin of the same muscle and %DET was used as a measure of synchronous activity. The %DET appeared to be a valid measure of synchronization yielding results comparable to those obtained with cross-correlation analysis. Increases in %DET (t = 64.59, P < 0.0001) highly correlated (r2 = 0.70, P = 0.0013) with pharmacologically induced increases in the synchronization activity of pairs of ECR motor units (t = 8.71, P < 0.0001). RQA may be used as an alternative methodology for testing synchronous motor unit behaviour from surface EMG under physiological and pathological conditions.     

Motor neuron firing range,axonal conduction velocity,and muscle fiber histochemistry in neuromuscular diseases

The voluntary discharge properties and axonal conduction velocity of single motor units were studied in patients with neuromuscular diseases with retained differentiation of the muscle fibers into type 1 and type 2, and in patients with late-onset hereditary distal myopathy in which muscle fibers have only intermediate histochemical properties. In the patients with muscle fiber differentiation, the findings were similar to those in normal subjects; that is, there was a continuum between motor units which fired tonically at low rates and had a low axonal conduction velocity, and motor units which fired phasically at high rates and had a high axonal conduction velocity. In the patients without muscle fiber differentiation, all motor units had intermediate firing properties and a low axonal conduction velocity. It is suggested that in chronic pathologic states, the differentiation of the muscle fiber histochemistry remains only as long as the differentiation of the motor neurons remains.     

Heart rate variability, sleep and sleep disorders

Heart rate (HR) is modulated by the combined effects of the sympathetic and parasympathetic nervous systems. Therefore, measurement of changes in HR over time (heart rate variability or HRV) provides information about autonomic functioning. HRV has been used to identify high risk people, understand the autonomic components of different disorders and to evaluate the effect of different interventions, etc. Since the signal required to measure HRV is already being collected on the electrocardiogram (ECG) channel of the polysomnogram (PSG), collecting data for research on HRV and sleep is straightforward, but applications have been limited. As reviewed here, HRV has been applied to understand autonomic changes during different sleep stages. It has also been applied to understand the effect of sleep-disordered breathing, periodic limb movements and insomnia both during sleep and during the daytime. HRV has been successfully used to screen people for possible referral to a Sleep Lab. It has also been used to monitor the effects of continuous positive airway pressure (CPAP). A novel HRV measure, cardiopulmonary coupling (CPC) has been proposed for sleep quality. Evidence also suggests that HRV collected during a PSG can be used in risk stratification models, at least for older adults. Caveats for accurate interpretation of HRV are also presented.     

Motor unit firing pattern of vastus lateralis muscle in type 2 diabetes mellitus patients

Introduction: We investigated the motor unit (MU) firing pattern in type 2 diabetes mellitus (T2DM) patients by means of multichannel surface electromyography (SEMG). Methods: Eight T2DM patients and 8 age‐matched, healthy men performed a ramp‐up contraction to 20% of maximal voluntary contraction (MVC). They also performed a sustained contraction at 10% of MVC during isometric knee extension. Multichannel SEMG signals recorded from the vastus lateralis muscle were decomposed with the convolution kernel compensation technique to extract individual MU firing patterns. Results: During the ramp contraction, the extent of MU firing modulation was significantly attenuated in T2DM. Variability of MU firing rate was significantly higher in T2DM at later periods during the sustained contraction. Conclusions: Our findings suggest that T2DM patients manifest characteristic MU activity patterns due possibly to some degree of neuromuscular impairment affecting the integrity of MU firing modulation. Muscle Nerve 48:806–813, 2013     

Short‐term training adaptations in maximal motor unit firing rates and afterhyperpolarization duration

In this study we investigated age‐ and training‐related adaptations in maximal motor unit firing rates and the duration of the motoneuron afterhyperpolarization (AHP) in the dorsiflexor muscles of the foot. Subjects included 30 young (21.9 ± 3.1 years) and 30 older (72.9 ± 4.6 years) individuals, who were randomly assigned to a control or training group. Maximal voluntary force (MVC), maximal motor unit firing rate, and motoneuron AHP duration were measured on two occasions. The training group participated in six dorsiflexor exercise training sessions between test and retest. At baseline, young subjects had higher MVC force and maximal motor unit firing rate, and shorter AHP duration, compared with older subjects. Young and older subjects in the trained group demonstrated a respective 17.4% and 19.8% increase in MVC force, a 6.8% and 24.3% increase in maximal MUFR, and a 7.4% and 14.2% decrease in AHP duration. These results indicate that age‐related changes in neuromuscular function are not a necessary consequence of aging. Muscle Nerve, 2010