Neuromuscular transmission at terminals of sprouted mammalian motor neurones

Motor nerve sprouting was induced in the tensor fasciae latae muscle of mice by partial denervation produced either by cutting (to prevent reinnervation) or crushing (to allow subsequent reinnervation) spinal nerve L4 unilaterally. The quantum content (m) of endplate potentials recorded intracellularly in vitro in the presence of high-Mg²⁺ and low-Ca²⁺ ion concentrations was determined up to 400 days later in non-reinnervated, reinnervated and contralateral control muscles. The muscles were then either fixed and stained with silver and cholinesterase for light microscopy, or fixed and examined in the electron microscope. The average value of m in control muscles increased by 4–5-fold as the animals matured in the 4 months following the operations. The average value of m at terminals of sprouted motor neurones in the absence of reinnervation also increased with time after partial denervation but was always less than the value in the corresponding control muscle. In electron micrographs of muscles following L4 section the nerve terminals closely apposed on average only two-thirds of the proportion of junctional folds apposed by terminals in control muscles. When muscles were reinnervated following L4 crush the average value of m at terminals of sprouted and reinnervating motor neurones equalled and sometimes exceeded m in contralateral control muscles. A proportion of muscle fibres had endplate potentials from reinnervating and sprouted axons, and the silver stain showed that these muscle fibres were innervated at the site of the original endplate. At these endplates the fraction of the total quantum content contributed by presumed sprout terminals fell significantly in the 4 months following L4 crush. It is concluded that: (i) in the absence of reinnervation, sprout terminals grow in size but a significant number never occupy all endplate site available to them; and (ii) in the presence of reinnervation, reinnervating axon terminals share some endplates with sprout terminals and grow at the expense of the sprout terminals which are eventually withdrawn from some shared endplates.     

Motor unit size estimation of enlarged motor units with surface electromyography

Surface EMG is hardly used to estimate motor unit (MU) characteristics, while its non-invasiveness is less stressful for patients and allows multi-electrode recordings to investigate different sites of the muscle and MU. The present study compares motor unit potentials (MUPs) obtained with surface EMG and macro EMG during voluntary contraction of the biceps brachii muscle of patients with enlarged MUs caused by prior poliomyelitis. Averaged surface MUPs were obtained by means of needle EMG (SMUP1) and surface EMG (SMUP2) triggering. The MUPs area and peak amplitudes correlated well when comparing the macro MUP and SMUP1 of the same MUs. When MU populations of different patients were compared, the SMUP1s and SMUP2s were equally sensitive to pathology as macro MUPs. In this, the late non-propagating positive wave (only present in unipolar recordings) is more robust than the triphasic propagating wave. Therefore, surface EMG can be used for detecting enlarged MUs. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:878–886, 1998.     

Role of motor unit structure in defining function.

Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge.     

Fatigue of chronically overused motor units in prior polio patients

This study was undertaken to investigate the mechanisms underlying fatigue of chronically overused motor units (MUs). The force of the tibialis anterior muscle (TA) and the firing properties of single MUs were studied during prolonged maximum voluntary effort in 10 prior polio patients selected such that daily living required all residual TA power. Almost all TA fibers were hypertrophic type I. Activities of intermyofibrillar succinate dehydrogenase (SDH) and calcium-stimulated myofibrillar adenosine triphosphatase (ATPase) were measured in single TA fibers from a representative patient. Neither insufficient motoneuron activation nor peripheral blocking of the electrical impulse played a major role in the loss of force during prolonged contraction or for slow recovery after contraction. The ratio of SDH to calcium-stimulated ATPase, representing the relation between energy resynthesis and energy utilization, was significantly (P < 0.001) lower in prior polio patients (0.230 ± 0.096) compared to control (0.515 ± 0.097) type I fibers. © 1996 John Wiley & Sons, Inc.     

The spectrum of concentric macro EMG correlations. Part I. Normal subjects.

Using a concentric macro electrode, both the concentric and macro action potentials of a motor unit were analyzed for duration, area, and amplitude. Eighty-six different motor units were analyzed from the tibialis anterior muscle in 10 normal subjects. The aim of this work was to compare concentric and macro action potential measurements of the same motor unit. The study revealed significant correlations between concentric and macro samples, with the concentric potential's area correlating better with the macro potential than its amplitude. This shows that the 10 to 15 muscle fibers studied by the concentric electrode serve as a good sample of the motor unit as a whole. We briefly review the technique used in concentric macro EMG, as well as describe the methods used for collecting and comparing both concentric and macro action potentials.     

Single fiber EMG in a congenital myasthenic syndrome associated with facial malformations

Six patients with a newly described genetic syndrome in Iraqi and Iranian Jews of congenital myasthenia associated with facial malformations were studied with voluntary and stimulation single fiber EMG (SFEMG). Voluntary SFEMG revealed abnormal jitter in all patients in both extensor digitorum communis (EDC) and orbicularis oculi (OOC) muscles, though much smaller in the clinically unaffected EDC. SFEMG study of OOC muscle by axonal stimulation at rates from 1 to 48 Hz showed the most increased jitter at the highest stimulation frequencies in the majority of end-plates, one-third of which showed maximal jitter at intermediate rates. These results may suggest a postsynaptic abnormality as the underlying cause for the neuromuscular transmission defect, and demonstrate the usefulness of SFEMG in the diagnosis of congenital myasthenia. © 1993 John Wiley & Sons, Inc.     

Effect of muscle-fiber velocity recovery function on motor unit action potential properties in voluntary contractions

Measurements of muscle-fiber conduction velocity during voluntary contractions have been used in the diagnosis of neuromuscular diseases. However, the velocity of propagation of action potentials depends on the interspike interval of activation due to the velocity recovery function (VRF) of muscle fibers. The comparison of muscle-fiber conduction velocity estimates between individuals may thus be influenced by differences in motor unit discharge rate. This study investigates action potential properties of motor units of the sternocleidomastoid muscle during voluntary modulation of discharge rate with the purpose of assessing the effect of the VRF on motor unit properties in voluntary contractions. Nineteen healthy men trained to control a target motor unit with feedback of surface multichannel electromyographic (EMG) signals. The subjects performed three 30-s contractions of cervical flexion/rotation modulating the discharge rate of the target motor unit from 6.6 +/- 1.6 pps to 28.0 +/- 6.4 pps. Action potential conduction velocity was correlated to instantaneous discharge rate (R = 0.38 +/- 0.21). Action potential conduction velocity, peak-to-peak amplitude, and duration varied between minimum and maximum discharge rate (P < 0.01; percent change 12.3 +/- 5.0, -11.8 +/- 9.9, and -12.9 +/- 7.3). Thus, the properties of surface motor unit action potentials vary with modulation of discharge rate. This has implications for the use of conduction velocity values measured during voluntary contractions to differentiate patient populations from healthy individuals and for the development of normative data.     

Fatigue-related changes in motor unit action potentials of adult cats.

The purpose of this study was to quantify the changes in motor-unit action potentials (MUAP) and force during a standard motor-unit fatigue test. MUAP waveforms were characterized by the measurement of amplitude, duration, area, and shape (as reflected in a coefficient of proportionality). Fatigue-resistant motor units exhibited small, but statistically significant, changes in MUAP amplitude and area during the fatigue test, whereas fatigable motor units displayed variable changes in MUAP amplitude, duration, and area. For all motor-unit types, the coefficient of proportionality did not change, and hence the change in MUAP area was proportional to the combined changes in amplitude and duration. The between- and within-train changes in MUAP were also distinct for the fatigue-resistant and fatigable motor units. Although several mechanisms could be responsible for the changes in the MUAP as the fatigue test proceeded, the dissociation of the time courses for MUAP and force indicated that these MUAP changes were not the principal reason for the decline in force under these conditions.     

The spectrum of concentric macro EMG correlations. Part II. Patients with diseases of muscle and nerve.

In the second part of this study we investigate the correlations between the concentric and conmac action potentials in motor units of individuals with diseases of muscle and nerve. We studied 86 myopathic and 86 neurogenic motor units and compared their concentric and conmac action potentials. In the patients with myopathy, we found that the concentric motor unit action potential's (MUAP) area correlates strongly with the conmac potential, even better than in normals, while its amplitude correlates less. In the neurogenic group, we found that both the concentric MUAP's area and amplitude correlated very well with their conmac counterpart, more so than in normals. Thus, in pathology, as in normals, measuring the concentric MUAP's area in addition to its amplitude adds to the diagnostic sensitivity of motor unit potential measurements. These findings are discussed in light of the known dynamic and architectural motor unit changes which take place in the myopathic and neurogenic motor unit.     

A study of motor unit structure by means of scanning EMG.

We used the scanning EMG technique to investigate the structure of human quadriceps muscle motor units. A group of healthy volunteers and 2 groups of patients with proven neurogenic or myogenic neuromuscular pathology have been studied. In total, 86 scans were obtained. An estimate of the motor unit territory (S) separates the 2 patient groups: the majority of territories of myogenic patients are smaller than 4 mm, whereas almost all motor unit territories of neurogenic patients are larger. However, the sizes of the pathologic units only occasionally exceed the upper and lower limits of normal units (2 to 8 mm). The myogenic scans show, on average, a much larger temporal dispersion (T) between the MUAPs within a motor unit than the normal scans. These findings are in accordance with observations with the same technique by others. For the neuropathic scans, there is a significant positive correlation between S and T, which is completely absent in myopathic scans. These observations are confronted with current morphometrical knowledge on motor unit physiology and anatomy.     

Nerve-muscle involvement in a large family with mitochondrial cytopathy: electrophysiological studies.

Thirteen patients with mitochondrial cytopathy were investigated. They represent different generations, ages, stages, and severities of the disease. All were assumed to have the same metabolic defect. The disease is a multisystem disorder with a metabolic defect located at complex 1 in the respiratory chain. Clinically, the disorder gives symptoms such as hearing loss, retinal pigmental degeneration, ataxia, cardiomyopathy, muscular fatiguability and neuropathy. The patients were investigated with nerve conduction studies, concentric needle EMG, SFEMG, and macro EMG examinations. Neurophysiologic studies revealed signs of myopathy in both the younger members and in those with slight muscular symptoms. In the more advanced stages, neuropathic changes of the axonal type were seen as well. Macro EMG was interpreted as indicating muscle fiber membrane abnormalities in the early stages. Single fiber EMG studies indicate that this metabolic defect does not disturb neuromuscular transmission.     

A new approach to motor unit estimation with surface EMG triggered averaging technique

A new method for estimating the number of motor units using a surface EMG triggered averaging technique is described. This method provides an estimation of mean motor unit potential (MUP) amplitude at different leveles of contraction, which can be utilized to estimate the number of motor units in a given muscle. Motor unit count estimated in abductor pollicis brevis (APB) muscle of 11 normal healthy subjects ranged from 131 to 371 with a mean of 246 ± 68. In our preliminary study of patients with lower motor neuron lesions, there was a significant reduction in the number of motor units. We believe our new noninvasive method of motor unit counting is a relatively simple and reproducible physiological technique.© 1995 John Wiley &Sons, Inc.     

Size does matter: The influence of motor unit potential size on statistical motor unit number estimates in healthy subjects

Objective

The statistical method of motor unit number estimation (MUNE) assumes that all motor unit potentials (MUPs) have the same size. The present study aims to evaluate the consequences of this assumption as well as its implications for the validity of statistical MUNEs.

Methods

We performed statistical and multiple point stimulation (MPS) MUNE with an array of 120 electrodes on the thenar muscles of 15 healthy subjects. These recordings allow isolation and quantification of the effect of non-uniform MUP size on MUNE, because the differences in submaximal CMAP size (and, hence, in MUNE) between electrodes are due almost entirely to differences in (summed) MUP size.

Results

We found no correlation between statistical and MPS MUNEs. Statistical MUNEs proved very sensitive to small variations in the “bandwidth” (variance) of the response series; MUNEs from electrodes only 8 mm apart could deviate by as much as 60%. This variation in bandwidth resulted from spatial (and, hence, size) differences between the contributing MUPs.

Conclusions

Statistical MUNEs are very sensitive to violation of the uniform MUP-size assumption, to an extent that blurs any correlation with MPS MUNE in healthy subjects.

Significance

Statistical MUNE cannot be used to detect mild to moderate motor unit losses.     

Concentric macro electromyography

Concentric EMG electrodes can record from a few (10 to 15) muscle fibers of a motor unit (MU). Macro EMG, is able to record from the majority of muscle fibers in the MU. The macro EMG electrode uses a single fiber action potential (SFAP) on one channel to trigger the time locked cannula (macro) response on the other channel. To study the concentric motor unit action potential (MUAP), alongside the macro potential, we built a needle electrode combining concentric and macro recording surfaces. The study of 240 motor units in 10 healthy subjects with the single fiber (SF macro) and concentric macro (conmac) electrodes revealed no significant differences between macro potentials areas and amplitudes obtained with either electrode. The ability to study a small and a large section of the motor unit simultaneously offers insights into the local or global nature of motor unit changes not otherwise available to the electromyographer. It also reveals which concentric parameters correlate best with the macro potential and, can even be of great help with the newer EMG signal decomposition techniques; by identifying each motor unit by its concentric and macro waveform simultaneously, it will allow for the "marking" of these motor units helping to reduce the risk of their misclassification when the concentric MUAP is used alone.     

Single motor unit variability with threshold stimulation in patients with amyotrophic lateral sclerosis and normal subjects

Repetitive nerve stimulation often shows responses with an abnormal decrement in patients with amyotrophic lateral sclerosis (ALS), suggesting instability of the neuromuscular junction; however, the pathophysiology and response characteristics of this instability are not clear. We evaluated response variability of 47 single motor units from 16 patients with ALS and 51 units from 10 normal subjects, acquired by delivering threshold stimuli sporadically at 0.5 HZ or less. In addition, in 46 other different single motor units obtained from 21 patients with ALS, variability was studied at both 1- and 3-HZ stimulation rates. Motor units from patients with ALS were significantly more variable than those from normal subjects, even when their larger amplitude was accounted for. This increased variability was not rate dependent. Response variability is a critical measure in the statistical method of motor unit number estimation and is attributed to variability in the number of units activated; the fact that variability of single motor units varies with disease state may be a potentially confounding factor in the application of the technique.     

F waves and motor unit size.

M responses and twitch contractions were evoked in single motor units (MUs) of the first dorsal interosseus muscle by intramuscular microstimulation of motor axons. Two-hundred nine MUs were studied in 21 subjects. Thirty-five MUs (17%) showed F waves in addition to M responses. Twitch force was used to provide an indirect measure of MU size; additionally, twitch contraction time was measured. There was no select group of MUs generating F waves with regard to the above contraction parameters. However, four of five MUs with very high twitch forces, above 70 mN, generated F waves. We conclude that MUs of all sizes produce F waves with similar probability. Only few MUs with very strong twitch forces, i.e., very large MUs, may be more subject to F-wave production and may be involved in the generation of the so-called repeater F waves.     

Determinants of mean motor unit size: Impact on estimates of motor unit number

The purpose of this study was to compare two fundamentally different methods of deriving the average surface-detected motor unit action potential (S-MUAP) size from which to calculate a motor unit number estimate (MUNE), namely: (1) the simple arithmetic average of S-MUAP parameter values; and (2) a computer-derived datapoint by datapoint average waveform which takes account of differences in S-MUAP shapes and durations. Multiple point stimulation was used to collect representative samples of between 11 and 20 S-MUAPs (mean 15 ± 2 SD) from the median-innervated thenar muscles of 20 healthy control subjects between 20 and 76 years of age (mean 48 ± 19 SD). The average S-MUAP size based on peak-to-peak amplitude, negative peak amplitude, and negative peak area measurements was calculated using the two different methods. The mean S-MUAP sizes based on the average waveform were significantly lower in all cases than those based on the simple average of S-MUAP parameter values. Differences tended to be greatest for MUNEs based on peak-to-peak amplitude (35%), less for negative peak amplitude (20%), and least for negative peak area (16%). © 1993 John Wiley & Sons, Inc.     

Long-duration polyphasic motor unit potentials in myopathies: a quantitative study with pathological correlation

In most myopathies, the duration of motor unit action potentials (MUAPs) is shorter than normal. However, polyphasic MUAPs of duration longer than 20% of the control mean, (long-duration polyphasic potentials, or LDPPs) may be seen. We therefore analyzed the incidence and meaning of LDPPs using quantitative MUAP analysis in 41 patients with different myopathies. The mean duration of all potentials was reduced in only 64% of patients because LDPPs increased the mean. When only simple potentials were considered, however, the mean duration was decreased in 95% of patients. This observation confirms the need to exclude LDPPs when calculating the mean duration of MUAPs for diagnosis. We found LDPPs most often in chronic polymyositis and in one patient with Becker Muscular Dystrophy. LDPPs are attributed to desynchronization of single-fiber potentials within the MUAP and may be due to slow conduction in regenerating muscle fibers.     

Macro electromyography and motor unit number index in the tibialis anterior muscle: differences and similarities in characterizing motor unit properties in prior polio

Our objective was to establish the usefulness of the noninvasive method of the motor unit number index (MUNIX) in a large muscle and to study how macro electromyography (EMG) and MUNIX complement each other in describing the motor units (MUs) in prior polio. MUNIX and macro EMG were performed in 48 tibialis anterior muscles in 33 prior polio patients. In addition, the reproducibility of MUNIX was investigated. It is shown that MUNIX can be used to characterize MUs with high reproducibility, even in a large muscle. As judged by MUNIX values, the patients had a 25% reduction of motor neurons, whereas the macro EMG indicated a loss of 60% of the neurons. Macro EMG showed more pronounced changes compared with control material than the MUNIX. One of the reasons for this finding may be the difference in MU populations studied with the two methods.