Single Human Motor Units Research Articles

The role of novel motor unit magnetic resonance imaging to investigate motor unit activity in ageing skeletal muscle.

Sarcopenia is a progressive and generalized disease, more common in older adults, which manifests as a loss of muscle strength and mass. The pathophysiology of sarcopenia is still poorly understood with many mechanisms suggested. Age associated changes to the neuromuscular architecture, including motor units and their constituent muscle fibres, represent one such mechanism. Electromyography can be used to distinguish between different myopathies and produce counts of motor units. Evidence from electromyography studies suggests that with age, there is a loss of motor units, increases to the sizes of remaining units, and changes to their activity patterns. However, electromyography is invasive, can be uncomfortable, does not reveal the exact spatial position of motor units within muscle and is difficult to perform in deep muscles. We present a novel diffusion‐weighted magnetic resonance imaging technique called ‘motor unit magnetic resonance imaging (MUMRI)’. MUMRI aims to improve our understanding of the changes to the neuromuscular system associated with ageing, sarcopenia and other neuromuscular diseases. To date, we have demonstrated that MUMRI can be used to detect statistically significant differences in fasciculation rate of motor units between (n = 4) patients with amyotrophic lateral sclerosis (mean age ± SD: 53 ± 15) and a group of (n = 4) healthy controls (38 ± 7). Patients had significantly higher rates of fasciculation compared with healthy controls (mean = 99.1/min, range = 25.7–161.0 in patients vs. 7.7/min, range = 4.3–9.7 in controls; P < 0.05. MUMRI has detected differences in size, shape, and distribution of single human motor units between (n = 5) young healthy volunteers (29 ± 2.2) and (n = 5) healthy older volunteers (65.6 ± 14.8). The maximum size of motor unit territories in the older group was 12.4 ± 3.3 mm and 9.7 ± 2.7 mm in the young group; P < 0.05. MUMRI is an entirely non‐invasive tool, which can be used to detect physiological and pathological changes to motor units in neuromuscular diseases. MUMRI also has the potential to be used as an intermediate outcome measure in sarcopenia trials.

Non-invasive imaging of single human motor units

ObjectiveTo determine the size, shape and distribution of single human motor units in-vivo in healthy controls of different ages. MethodsA novel diffusion-weighted magnetic resonance imaging (MRI) technique was used in combination with in-scanner electrical stimulation to quantify the shape, cross-sectional area, and dimensions of individual motor units in 10 healthy subjects. ResultsThirty-one discrete motor units were studied. The majority were elliptical or crescent shaped, but occasional split motor units were observed. The mean motor unit cross sectional area was 26.7 ± 11.2 mm2, the mean maximum dimension was 10.7 ± 3.3 mm, and the mean minimum dimension was 4.5 ± 1.2 mm. Subjects aged over 40 had significantly larger maximum dimensions than those below this age (p < 0.05). ConclusionsMotor unit MRI (MUMRI) is a novel technique capable of revealing the size, shape and position of multiple motor units in human muscles. It is reproducible, non-invasive, and sufficiently sensitive to detect physiologically relevant changes in motor unit morphology with age. SignificanceTo our knowledge, these results provide the first imaging assessment of human motor unit morphology. The technique shows promise both as a diagnostic tool and as a biomarker in longitudinal studies of disease progression.

Ia Afferent input alters the recruitment thresholds and firing rates of single human motor units.

Vibration of the patellar tendon recruits motor units in the knee extensors via excitation of muscle spindles and subsequent Ia afferent input to the alpha-motoneuron pool. Our first purpose was to determine if the recruitment threshold and firing rate of the same motor unit differed when recruited involuntarily via reflex or voluntarily via descending spinal pathways. Although Ia input is excitatory to the alpha-motoneuron pool, it has also been shown paradoxically to inhibit itself. Our second purpose was to determine if vibration of the patellar tendon during a voluntary knee extension causes a change in the firing rate of already recruited motor units. In the first protocol, 10 subjects voluntarily reproduced the same isometric force profile of the knee extensors that was elicited by vibration of the patellar tendon. Single motor unit recordings from the vastus lateralis (VL) were obtained with tungsten microelectrodes and unitary behaviour was examined during both reflex and voluntary knee extensions. Recordings from 135 single motor units showed that both recruitment thresholds and firing rates were lower during reflex contractions. In the second protocol, 7 subjects maintained a voluntary knee extension at 30 N for approximately 40-45 s. Three bursts of patellar tendon vibration were superimposed at regular intervals throughout the contraction and changes in the firing rate of already recruited motor units were examined. A total of 35 motor units were recorded and each burst of superimposed vibration caused a momentary reduction in the firing rates and recruitment of additional units. Our data provide evidence that Ia input modulates the recruitment thresholds and firing rates of motor units providing more flexibility within the neuromuscular system to grade force at low levels of force production.

Dissociation of the electrical and contractile properties in single human motor units during fatigue.

The surface EMG area often exhibits progressive enlargement during a submaximal fatiguing contraction, but the underlying reasons still remain uncertain. Fatigue-induced changes in the surface-detected motor unit action potentials (S-MUAPs) of 10 human thenar motor units (MUs) with widely differing physiological properties were examined. After 2 min of repetitive 40-Hz stimulation, the size of the S-MUAPs of all MUs increased, the magnitude of which was negatively correlated with their tetanic tension changes. These findings suggest that during muscle fatigue, in addition to reflecting recruitment of new MUs and increases in firing rates of the active MUs, the surface EMG may also be markedly influenced by changes in the S-MUAPs, especially in fast fatigable muscles.

Spindle and motoneuronal contributions to the phase advance of the human stretch reflex and the reduction of tremor.

1. The human stretch reflex is known to produce a phase advance in the EMG reflexly evoked by sinusoidal stretching, after allowing for the phase lag introduced by simple conduction. Such phase advance counteracts the tendency to tremor introduced by the combined effect of the conduction delay and the slowness of muscle contraction. The present experiments confirm that the EMG advance cannot be attributed solely to the phase advance introduced by the muscle spindles, and show that a major additional contribution is provided by the dynamic properties of individual motoneurones. 2. The surface EMG was recorded from biceps brachii when two different types of sinusoidally varying mechanical stimuli were applied to its tendon at 2-40 Hz. The first was conventional sinusoidal displacement ('stretch'); the spindle discharge would then have been phase advanced. The second was a series of weak taps at 103 Hz, with their amplitude modulated sinusoidally ('modulated vibration'). The overall spindle discharge should then have been in phase with the modulating signal, since the probability of any individual 1 a fibre responding to a tap would increase with its amplitude. The findings with this new stimulus apply to motoneurone excitation by any rhythmic input, whether generated centrally or peripherally. 3. The sinusoidal variation of the EMG elicited by the modulated vibration still showed a delay-adjusted phase advance, but the value was less than that for simple stretching. At 10 Hz the difference was 70-80 deg. This was taken to be the phase advance introduced by the spindles, very slightly underestimated because of the lags produced by tendon compliance in transmitting sinusoidal stretch to the muscle proper. The adjusted phase advance with modulated vibration was taken to represent that introduced by the reflex centres, undistorted by tendon compliance. At 10 Hz the reflex centres produced about the same amount of phase advance as the muscle spindles. 4. At modulation frequencies above 10 Hz the adjusted central phase advance remained approximately constant. However, when the frequency was reduced to below 6 Hz the central phase advance decreased. The depth of EMG modulation (reflex gain) also fell rapidly, starting from a slightly higher frequency. Thus the central phase advance mechanisms behave like a high-pass filter. 5. A simple model of the motoneurone, incorporating synaptic noise and an after-hyperpolarization, was tested with sinusoidal inputs and gave a phase advance over a wide range of frequencies. The effect was tightly linked to two particular facets of the motor discharge; these were the ratio between the stimulus frequency and the mean firing rate (the 'carrier frequency' of the unit), and the coefficient of variation of the interspike interval distribution. The gain rose to a maximum at the carrier frequency, while the phase advance showed a maximum at 0.8 of the carrier. The more regular the discharge, the greater were these effects. The phase advance might increase to above 90 deg, showing that the motoneurone potentially provides a major contribution to the phase advance of the stretch reflex. Related effects have already been observed in other neuronal models and for the discharge of the muscle spindle, without their significance for the motoneurone being appreciated. In essence, a rhythmically firing neurone is particularly affected by a rhythmic stimulus when the two frequencies approximately coincide. 6. Recording from single human motor units confirmed the role of the 'carrier frequency' in determining the phase advance with sinusoidal inputs. In particular, for both stretching and modulated vibration, the phase advance of the response elicited by a fixed sinusoidal stimulus changed appropriately when the firing rate of the unit varied 'spontaneously' over a long recording period. 7. Thus a combination of modelling and experiment has shown that the motoneurones themselves produce a significant phase advance.

A method for the longitudinal study of human thenar motor units.

Methods currently available to study the electrophysiological and contractile properties of single human motor units (MUs) preclude the same MU from being studied on repeated occasions. We have developed a method which allows single thenar MUs to be studied longitudinally. Sites were located along the median nerve where, using percutaneous stimulation, it was possible to selectively activate a single thenar motor axon as determined by: (a) the presence of an "all-or-nothing" surface-detected motor unit action potential (S-MUAP); (b) the occasional presence of F-responses identical in size and shape to the direct S-MUAP; (c) excitation thresholds widely separated from the next highest threshold motor axon so as to allow high frequency stimulation. To ensure that the same motor axon had been located and stimulated in successive studies, additional criteria included: (a) the motor axon was found at approximately the same site along the nerve; (b) the threshold for excitation remained widely separated from the next highest threshold motor axon; (c) the shape of the S-MUAP was almost identical on repeated studies; (d) S-MUAP and F-response latencies were similar. This method provides, for the first time, the ability to track longitudinally the electrical and contractile properties of single MUs in health and during the course and treatment of disease.

Measurement of contractile and electrical properties of single human thenar motor units in response to intraneural motor-axon stimulation

1. A method is described for measuring contractile properties of single human motor units. Conventional human microneurographic techniques were adapted to stimulate individual motor axons in the median nerve, with the use of negative current pulses and a tungsten microelectrode, while recording motor-unit electromyographic activity (EMG) and isometric force responses from the thenar muscles. 2. EMG signals were recorded from both proximal and distal thenar muscle surfaces. Force was recorded in two directions (thumb flexion and abduction). This allowed calculation of the direction and magnitude of resultant force exerted by each unit. 3. Data accepted as originating from a single unit satisfied all the traditional "all-or-none" criteria. Additional criteria also required the following: 1) a wide safety margin between the threshold for unit activation and the current intensity needed to elicit responses from other units; 2) that the characteristic direction in which each unit generated force did not change during the recording period; and 3) whenever F-responses were encountered, the second EMG waveform was identical to the first--a highly improbable event if more than one unit had been excited. 4. Respiration and blood pressure waves introduced baseline fluctuations that distorted the force measurements. These fluctuations were minimized by synchronizing stimuli to the pulse pressure cycle and resetting the baseline electronically just before stimulus onset. 5. Combining motor-axon stimulation at a site remote from the muscle with electronic resetting of the force baseline and delivery of stimuli at fixed intervals after the pulse pressure waves allowed the full time course of human motor-unit twitch and tetanic force and EMG signals to be recorded accurately without signal averaging.

Axonal conduction velocity and force of single human motor units.

Tungsten microelectrodes of the type used for microneurography have been used to record motor units selectively from the first dorsal interosseous and abductor pollicis brevis muscles of normal subjects and patients who had had complete sections of the ulnar or median nerve. After determining the recruitment threshold and the twitch tension (spike-triggered averaging) of a single unit, its nerve was stimulated at the wrist and the elbow using surface electrodes. By adjusting the position of the surface electrode and the stimulus intensity and by using computerized subtraction of responses just above and below threshold for a given unit, the same motor unit could often be identified in response to stimulation at both sites and its conduction velocity determined. The twitch tension and recruitment threshold of the motor units were closely correlated with the conduction velocity of the motor axons in normal subjects. Preliminary data from patients suggests that this method should be applicable to patients with a number of neuromuscular disorders.

Variations in the recruitment force threshold of single human motor units with knee and hip joint angles

Variations in the recruitment force threshold of single human motor units with knee and hip joint angles

Firing properties of single human motor units during locomotion.

The discharge properties of single motor units in the short extensors of the toes were studied during normal locomotion using electromyographic recordings which permitted the identification of single motor unit potentials. The single motor units were recruited in the same order during slowly increasing speed of locomotion as they were during slowly increasing voluntary tension, i.e. motor units with low axonal conduction velocity were recruited before motor units with higher conduction velocity. Low threshold units fired five to ten times at 80-40 ms intervals in each step cycle during walking at normal speed. Motor units with moderately high thresholds fired once or only a small number of times in each cycle at shorter interspike intervals. High threshold motor units did not participate in the step cycle during walking at normal speeds but fired in short high-frequency bursts in corrective movements.

The fatigue of voluntary contraction and the peripheral electrical propagation of single motor units in man

1. Single human motor units from the short extensors of the toes were classified by their voluntary threshold and axonal conduction velocity. The voluntary discharge intervals, and the shortest discharge intervals at which action potentials were conducted to the muscle fibres, were studied during maximal voluntary effort maintained for 1 min, and were compared with the intervals calculated to be necessary for full fusion.2. Electromyographic techniques were used. High selectivity of the recordings was obtained after blocking of the main motor nerve with lidocaine in subjects with an accessory innervation of just a few motor units or 6 months after lesions to intramuscular nerve twigs, when the muscle-fibre density within the motor units was increased.3. For a whole minute of maximal voluntary effort, motor units with low threshold and low conduction velocity fired tonically at a rate that should have been sufficient for maximal tension. These intervals were longer than the intervals at which blocking occurred.4. In ordinarily motivated and untrained subjects, motor units with high threshold and high conduction velocity fired tonically at intervals sufficient for full tension for some seconds. Under these circumstances the voluntary intervals were longer than the critical ones.5. Through extraordinary motivation and training, motor units with high threshold and high conduction velocity could also be driven tonically for 20-60 s at the high rates required for full tension. The critical intervals then approached the voluntary ones. Blockings occurred and increased in frequency as the contraction continued.6. When motor units with high threshold and high conduction velocity were tetanized electrically at 20 Hz, which was the lowest discharge rate of these units in tonic voluntary contraction, blockings occurred within 60 s.7. The role of the peripheral block is discussed in relation to loss of tension in prolonged voluntary contraction.

Firing properties of single human motor units on maintained maximal voluntary effort.

The discharge properties on maintained maximal voluntary effort, axonal conduction velocity (a.c.v.) and contraction time (c.t.) of single human motor units were studied. Electromyographic (EMG) techniques were used and sufficient selectivity was obtained after repeated lesions to the terminal nerve twigs and consequent collateral sprouting, or by blocking the main muscle nerve in subjects with an accessory nerve supplying just one or a few units, or using high impedance wire electrodes. Most units with a.c.v. above 45 m/s and c.t. below 50 ms had maximal voluntary firing rates of about 50 Hz. On prolonged maximal effort, however, their rates rapidly decreased and after some seconds to a minute they ceased to respond tonically. As long as their motoneurons fired their EMG potentials were mainly intact and their twitch tension was significant. Most units with a.c.v. below 40 m/s and c.t. above 60 ms fired initially at 30 Hz, decreased slowly in firing rate and continued at 20 Hz for some minutes. We conclude that there is a central fatigue of units with short c.t. and high a.c.v. which protects their peripheral regions from severe exhaustion, but that there is no significant central fatigue of units with long c.t. and low a.c.v. We emphasize, however, that most units are intermediate in their properties.