Abnormal single motor unit behavior in the upper motor neuron syndrome

We studied the discharge pattern of single motor units (SMUs) in the left and right biceps muscles from a patient with nonspastic weakness of the left arm. Detailed statistical analysis of the behavior of discharge patterns of 4 of 4 single motor units on the affected side showed abnormalities with characteristic features of an upper motor neuron lesion. Five out of 5 single motor units recorded from the right biceps were normal. An upper motor neuron lesion affecting the left arm, predicted by our results, was confirmed by magnetic resonance imaging (MRI), which showed a lesion in the right precentral gyrus. It appears that changes in single motor unit firing characteristics, caused by an upper motor neuron lesion, can be detected at a time when there is no evidence of increased "tone" and/or hyperreflexia (spasticity) in the affected extremity.     

Study of single motor unit discharge patterns using 1/f process model

We developed a technique to study temporal discharge patterns of single motor units using 1/f process model, whose fractional parameter γ was shown to be a useful indicator for distinguishing between discharge behaviors of single motor units of normal subjects and patients with upper motor neuron lesions. We have studied a total of 47 motor units in 3 normal subjects, and 41 in 3 patients with upper motor neuron lesions from biceps and extensor digitorum communis muscles during steady contraction. The parameter γ was estimated with an algorithm based on wavelet analysis. The mean value of γ in patients was 1.52, and the mean value of γ in normal subjects was −0.06. These results suggest that 1/f process can be used to document the impaired motor control mechanisms at single motor unit level. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 293–298, 1997.     

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.     

Reproducibility of motor unit number estimation in individual subjects

Although the reproducibility of motor unit number estimation (MUNE) for groups of subjects has been studied, there is little such data for individuals. Prediction intervals represent a tool to study individual MUNE reproducibility and represent the range of values expected for a future MUNE if the true number of motor units remains unchanged. MUNE was performed using the statistical method on 48 normal individuals. The prediction interval was found to be a function of the intrasubject coefficient of variation. Using a commercial manufacturer's recommended technique and software, prediction intervals were found to be so broad as to be of uncertain value. We found that by averaging two MUNE observations for each determination, and using the method of weighted averages for calculating the size of an average single motor unit potential, the intrasubject coefficient of variation was reduced from 16.48% to 8.77%, and the 90% prediction interval became sufficiently narrow to be clinically useful. False-negative rates were also lowered substantially using these techniques. Thus, simple modifications of an existing MUNE program improved the clinical utility of this program for the longitudinal study of patients in whom changes in motor unit number over time are of importance, such as those with motor neuron diseases.     

The stimulus-response curve and motor unit variability in normal subjects and subjects with amyotrophic lateral sclerosis

The behavior and stability of motor units (MUs) in response to electrical stimulation of different intensities can be assessed with the stimulus-response curve, which is a graphical representation of the size of the compound muscle action potential (CMAP) in relation to stimulus intensity. To examine MU characteristics across the whole stimulus range, the variability of CMAP responses to electrical stimulation, and the differences that occur between normal and disease states, the curve was studied in 11 normal subjects and 16 subjects with amyotrophic lateral sclerosis (ALS). In normal subjects, the curve showed a gradual increase in CMAP size with increasing stimulus intensity, although one or two discrete steps were sometimes observed in the upper half of the curve, indicating the activation of large MUs at higher intensities. In ALS subjects, large discrete steps, due to loss of MUs and collateral sprouting, were frequently present. Variability of the CMAP responses was greater than baseline variability, indicating variability of MU responses, and at certain levels this variability was up to 100 microVms. The stimulus-response curve shows differences between normal and ALS subjects and provides information on MU activation and variability throughout the curve.     

Motor unit number estimates and quantitative motor unit analysis in healthy subjects and patients with amyotrophic lateral sclerosis

Limitations associated with global measures of function in patients with amyotrophic lateral sclerosis (ALS) and the qualitative nature of needle electromyography have stimulated the development of alternate means of monitoring disease severity and progression in ALS. Thus, the objective of this study was to examine the ability of one these techniques, decomposition-based quantitative electromyography (DQEMG), to obtain electrophysiological data, including motor unit number estimates (MUNEs), from a group of patients with ALS. The first dorsal interosseous and biceps brachii muscles were studied in 10 healthy subjects and 9 patients with ALS. Following the acquisition of a maximum M wave, needle- and surface-detected EMGs were collected simultaneously during 30-second contractions performed at 10% of the maximum voluntary contraction force to obtain motor unit potential (MUP) trains. DQEMG was then used to extract the surface-detected MUP associated with each MUP train, the mean size of which was divided into the maximum M wave to obtain a MUNE. The results suggest that quantitative electrophysiological data obtained using DQEMG are representative of the pathophysiological changes in the lower motor system in ALS patients, supporting its use in studies documenting the natural history and progression of the disease.     

Variability of motor unit discharge and force fluctuations across a range of muscle forces in older adults

Variability of motor unit discharge is a likely contributor to the greater force fluctuations observed in old adults at low muscle forces. We sought to determine whether the variability of motor unit discharge rate underlies the fluctuations in force during steady contractions across a range of forces in young (n = 11) and old (n = 14) adults. The coefficient of variation (CV) for discharge rate and force were measured during a force-matching task as the first dorsal interosseous muscle performed isometric contractions. The recruitment thresholds of the 78 motor units ranged from 0.04% to 34% of maximal voluntary contraction (MVC) force. The CV for discharge rate ranged from 7.6% to 46.2% and was greater (P < 0.05) for old adults (21.5% +/- 7.7%) than young adults (17.3% +/- 8.1%). Although the CV for force was similar for young and old subjects (2.53% +/- 1.6%) across all target forces, it was greater for old adults at the lowest forces. Furthermore, there was a positive relation (r2 = 0.20, P < 0.001) between the CV for force and the CV for discharge rate across the range of recruitment thresholds. This relation was significant for old adults (r2 = 0.30, P < 0.001), but not for young adults (r2 = 0.06, P > 0.05). Thus, the normalized variability (CV) of motor unit discharge was greater in old adults and was related to the amplitude of force fluctuations across a broader range of forces than previously examined. These findings underscore the contribution of variability of motor unit activity to motor output in normal human aging.     

Motor unit discharge behaviors in stroke patients

We studied 60 motor units from abductor pollicis brevis, first dorsal interosseous, and abductor digiti minimus muscles in 18 patients with upper motor neuron lesions. Both fractional process parameters and serial correlation coefficients were estimated. The results suggest that both serial correlation coefficients and fractional process parameters can be used to objectively document upper motor neuron disorders in stroke patients. However, each of them may be more sensitive to distinct central motor regulatory mechanisms. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1502–1506, 1998     

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.     

Validity of electromyograms and tension as a means of motor unit number estimation

The purpose of this study was to validate three different techniques for obtaining motor unit number estimates of the rat medial gastrocnemius muscle. These consisted of two electromyographic techniques using unprocessed and digitally averaged unitary muscle action potentials, and one mechanical technique. We also injected subunit B of cholera toxin into this muscle and counted the number of spinal motor neurons labeled by the toxin. Our results revealed that a motor unit number estimate obtained by using the unprocessed unitary muscle action potential was statistically different from the actual number of motor neurons. The other two motor unit number estimates, however, were not statistically different from the actual motor neuron number. These two methods thus seem more appropriate than the first electromyographic method for obtaining an accurate motor unit number estimate. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20, 552–560, 1997.     

Galvanic vestibular stimulation alters the onset of motor unit discharge

We have previously shown that galvanic vestibular stimulation (GVS) can modulate the amplitude of the passive soleus H-reflex. This study examined whether the response resulted from a general change in excitability of the motoneuron pool or a specific modulation of individual motor units (MUs). Subjects performed slow isometric plantarflexor actions in a prone lying and kneeling position until the discharge of a single gastrocnemius MU was detected. During randomly selected trials, a 1-mA bipolar, binaural galvanic stimulus was triggered just prior to the start of plantarflexor activity. With the knee extended and the medial gastrocnemius (MG) at a long muscle length, GVS did not have an effect on MU activity. However, when the knee was flexed and the MG muscle was shortened, GVS significantly modified the onset of activation and the initial firing frequency of MUs. This may reflect a change in the gain of the presynaptic inhibitory mechanisms that act on the motoneuron pool once a muscle reaches a shortened, nonoptimal force-producing length. Thus, GVS may provide an important research tool for activating descending vestibulospinal pathways that act on lower-limb motoneurons and may be applied to test the integrity of the spinal cord.     

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.     

Adaptations in maximal motor unit discharge rate to strength training in young and older adults

Six young (mean = 23 years) and 6 older (mean = 76 years) adults participated in isometric resistance training 5 days/week for 6 weeks. The task involved isometric fifth finger abduction. Maximal motor unit discharge rates (MUDRs) were obtained from the abductor digiti minimi of each hand at 0, 2, 14, and 42 days of training using a quadrifilar needle electrode and automatic spike recognition software. In agreement with previous findings, maximal MUDR at baseline was significantly lower in older adults (P < 0.001), averaging 51.5 (+/-17.13) HZ in young and 43.3 (+/-14.88) HZ in older adults. In response to resistance training, maximal voluntary force increased 25% in young and 33% in older subjects (P < 0.001). Maximal MUDR increased significantly (11% young, 23% older) on day 2 [F(3,36) = 2.58, P < 0.05], but in older subjects returned to baseline levels thereafter. These adaptations in abductor digiti minimi MUDR suggest a two-part response to strengthening fifth finger abduction: early disinhibition followed by altered MU activation.Copyright 2001 John Wiley & Sons, Inc.     

Effect of small motor unit potentials on the motor unit number estimate

Small surface motor unit potentials (S-MUPs) may have a negative influence on the variability of the motor unit number estimate (MUNE). According to published consensus criteria S-MUPs with a negative peak amplitude smaller than 10 muV should be omitted. The effect of omitting small S-MUPs on the MUNE was evaluated using a simulation model. The model incorporated a healthy and amyotrophic lateral sclerosis (ALS) distribution formed with real S-MUPs. Using a random drawing process the MUNE was calculated with and without small S-MUPs. In the healthy population 27% of all S-MUPs were small. MUNE determined without these S-MUPs was marginally less variable. However, MUNE values dropped about 24% at a sample size of 20. In ALS, only 12% of the total population of 130 S-MUPs were small. MUNE dropped about 12% without the small S-MUPs. By omitting small S-MUPs the differences between the healthy and ALS distributions become smaller. Therefore, incorporating small S-MUPs in the estimate is suggested.     

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.     

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.     

Motor unit number estimation by spatial-temporal summation of single motor unit potentials

Current techniques for motor unit number estimation (MUNE) rely on the amplitude of the compound muscle action potential (CMAP) evoked by supramaximal stimulation and mean amplitude of single motor unit potentials (SMUPs). The phase cancellation during summation is not considered. We developed a technique to address this issue. Slow and fast types of motor unit potentials were collected from 5 normal subjects from their abductor pollicis brevis muscles by low-level voluntary contractions, and near-threshold nerve stimulation, respectively. Two of each type of SMUPs were used as templates for reconstructing the best fitted CMAP using a feed-forward neural network. The total number of SMUPs simulated from the four templates during the reconstruction served as MUNE. The mean MUNE was 222 ± 98. The technique is simple and noninvasive, and may be applied in the future for MUNE in patients. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 461–468, 1997     

Progressive motor unit loss in the G93A mouse model of amyotrophic lateral sclerosis is unaffected by gender

We examined whether there are gender differences in the progressive loss of functional motor units in SOD1^G93A transgenic mice. Isometric muscle and motor unit twitch contractions were recorded in fast‐ and slow‐twitch muscles in response to stimulation of the sciatic nerve. Using a modified motor unit number estimation technique (ITS‐MUNE), we found that motor unit numbers declined rapidly from 40 to 90 days of age during the asymptomatic phase of ALS in fast‐ but not slow‐twitch hindlimb muscles of both male and female mice. There was a corresponding decline in twitch and tetanic contractile forces of the fast‐twitch muscles. Gender did not affect the progressive loss of motor units and associated decline in force production. We conclude that gender does not alter progressive, muscle‐specific motor unit loss in ALS, even though gender does influence disease onset. Muscle Nerve 39: 318–327, 2009     

Motor unit number index (MUNIX): principle, method, and findings in healthy subjects and in patients with motor neuron disease

The motor unit number index (MUNIX) is a method for assessment of number and size (MUSIX) of motor units (MUs) using the compound muscle action potential (CMAP) and surface electromyographic interference pattern (SIP). This method was used to study the hypothenar muscle in 34 healthy subjects to define normal range, and to study reproducibility. Four healthy subjects and 13 patients with amyotrophic lateral sclerosis (ALS) were studied serially over a 1-year period. In healthy subjects, MUNIX showed good reproducibility. In serial studies, healthy subjects showed no change in the CMAP amplitude and MUNIX. ALS patients with minimal change in CMAP amplitude had a significant drop in MUNIX and increase in MUSIX, indicating MU loss compensated by reinnervation. When the CMAP changed significantly (>30%) in 1 year, the CMAP and MUNIX decreased in parallel. MUNIX would be useful to study MU loss in degenerative diseases of motor neurons. Muscle Nerve 42: 798-807, 2010.