The Motor Unit. Anatomy and Physiology. ARTHUR WM. ENGLISH and STEVEN L. WOLF*

Transcription

1 The Motor Unit Anatomy and Physiology ARTHUR WM. ENGLISH and STEVEN L. WOLF* The physiological and anatomical properties of mammalian motor units are discussed, and the results of human and animal studies are compared. A physiological organization of motor units based on the mechanical properties of their associated muscle units is examined. It is concluded that such an organizing principle has broad universal application in both animal and human studies. An anatomical organization of muscle units by their association with their physiological properties and the histochemical profile of their muscle fibers is also considered. The anatomical organizing principle also has broad-ranging applicability. The organization of muscle units according to muscle architecture and innervation patterns is described and its potential applicability to considerations of muscle structure and function is discussed. It is concluded that a number of gaps in our knowledge of muscle unit organization have been identified, especially among human studies, but the potential to fill these gaps rapidly is great. Key Words: Motor activity; Motor units, anatomy and physiology; Muscle units. The motor unit was termed by Sherrington the "final common path," because it is through motor units that all motor commands must be passed to produce movement. 1 A motor unit consists of a motor neuron, its axon, and what is referred to as the muscle unit, that is, all of the musclefibersthe motor neuron innervates. 2 The structural and functional organization of the central elements of motor units, the motor neurons, is discussed by Burke, 3 Henneman, 4 and Stein and Bertold. 5 This article is a discussion of our current knowledge of the anatomical and physiological organization of the peripheral elements, muscle units, and a comparison of animal and human research in this area. It is hoped that this review might also provide a general basis for careful and detailed analyses of muscle structure and function that include consideration of the anatomical and physiological properties of muscle units. PHYSIOLOGICAL PROPERTIES OF MUSCLE UNITS Animal Studies One of the most widely accepted views in all of motor unit physiology has been the classification of * Direct correspondence to Dr. Wolf. motor units proposed in various studies by Burke and co-workers. 6-8 Their studies, as well as several other studies, have given rise to the classification scheme shown in Table 1. Motor units are classified mainly according to the mechanical properties of their associated muscle units. Two reliable criteria used to type units are the waveform of contractile force during unfused tetani ("sag") and the resistance of the muscle unit to fatigue. Correlated with these two criteria for motor unit identification are a number of other variables, such as maximum tetanic tension, twitch-tetanus ratio, twitch potentiation, and twitch contraction time. Burke et al, in different studies, have thus classified cat hindlimb motor units as fast- or slow-twitch, and as fatigable or fatigue-resistant. 7, 8 They have proposed that the sag in tension records, noted when a muscle unit is stimulated at intervals slightly longer (1.25x) than its twitch contraction time, is the most reliable way of differentiating fast-twitch from slowtwitch units. Fast-twitch units show a sag (Fig. 1); slow-twitch units do not. Stephens and Stuart 9, 10 and Goslow et al 11 have argued persuasively that twitch contraction time provides a less ambiguous description of muscle unit types. Fast-twitch units have timeto-peak tension of less than 40 msec; slow-twitch units contract more slowly. Widespread agreement exists about identification of the fatigability of muscle units, and a fatigue index Volume 62 / Number 12, December

2 TABLE 1 Physiological and Histochemical Properties of Muscle Units a Unit type Fast-twitch fatigable (FF) Fast-twitch fatigueresistant (FR) Fast-twitch intermediate (Fint) Slow-twitch (S) Twitch Contraction Time (msec) Maximum Tetanic Tension (gm-f) Sag in Unfused Tetanus yes yes yes no Twitch Potentiation b moderate large small Twitch :Tetanus Ratio Fatigue Index <0.25 > >0.75 a Data for cat medial gastrocnemius muscle as reported by Burke 7 and Burke et al 8, 31 unless noted. b Discussed in Stephens and Stuart. 9 c Supposition. Fiber Type llb lla c lla c I has been calculated. 12 The fatigue index is the ratio of the tetanic tension produced after two minutes of intermittent stimulation (1 train/sec, 13 pulses/train at 40 pps) to that produced before such repeated stimulation. Fatigue indexes greater than 0.75 are indicative of fatigue-resistant units, and fatigable units have fatigue indexes of less than Three groups of motor units were originally proposed by Burke et al: fast-twitch fatigable (FF), fasttwitch fatigue-resistant (FR), and slow twitch (S). Type S units (Fig. 1) generally have a time-to-peak tension greater than 40 msec, produce small twitch and tetanic tensions, display no sag in unfused tetani, and are very resistant to fatigue (fatigue index > 0.75). Type FF units have a time-to-peak tension of less than 40 msec, produce very large twitch and tetanic tensions, display a sag during an unfused tetanus, and are readily fatigued by repeated stimuli (fatigue index < 0.25). Type FR units are somewhat intermediate: they are fast contracting but slightly slower than type FF units; they are resistant to fatigue (fatigue index > 0.75); and they produce twitch and Fig. 1. Panels A through D demonstrate criteria for classification of mammalian muscle units. Panels A and B are isometric force records obtained from stimulation of a single muscle unit at an interstimulus interval that is 1.25 times its twitch contraction time. The solid lines are the unfused tetanic responses of the unit. The dashed lines are the superimposed single twitches. Fast-twitch units display a "sag" in the tension record (A), slow-twitch units do not and often show some potentiation (B). Panels C and D show the results of a fatigue test. The units were stimulated at 40 pps for 330 msec every second for two minutes. The larger force record is from the first stimulus presentation, the lower record from the 120th. Fatigable units (C) display a drop in force to less than 0.25 of the initial level. Fatigueresistant units (D) show a drop that is not more than 0.75 of the initial level. All data are from English and Weeks. 18 (Scale bars: A-C, horizontal =100 msec, vertical =10 gm-f; D, horizontal = 100 msec, vertical = 1 gm-f.) 1764 PHYSICAL THERAPY

3 tetanic tensions that are smaller than those produced by type FF units and larger than those of type S units. Several researchers have identified units with fatigue properties between those of FF and FR/S units (fatigue index > 0.25 and < 0.75) and have considered these a fourth type of motor unit which 6, they termed Fint units. Although this classification scheme recently has been applied to various muscles, most of the available information about the physiological organization of mammalian motor units has come from studies of the medial gastrocnemius muscle of the cat. The reason this classification scheme is so widely accepted is that, almost without exception, it has proven a useful means of examining all mammalian motor units (Tab. 2). Studies of motor units in other cat hindlimb muscles, 12, cat foot muscles, 21 cat forelimb muscles (B. Botterman, 1981, personal communication), and different rat hindlimb muscles 22 have all shown that this same basic physiological organizing principle can be applied. Human Studies Human motor units with the following characteristics tend to be classified as tonic motor units: low threshold for maintained voluntary contraction, long contraction times, low twitch-tension, high resistance to fatigue, small amplitude action potentials, and slow conduction velocities. Conversely, phasic motor units tend to be recruited at high levels of voluntary contraction, display short contraction times and high twitch-tensions, are not fatigue-resistant, and show large amplitude action potentials and fast conduction velocity. In this sense, human motor units share many of the characteristics delineated in animal studies. As shown in Table 3, the number of studies designed to assess physiological components of human motor units is somewhat limited. This situation has been dictated mainly by limitations in technique and technology. In particular, it is difficult to accurately assess phasic motor units because the high levels of muscle tension often needed to recruit phasic motor units can be maintained only for a few seconds before the recording electrodes may become dislodged or reoriented. Even highly selective single-fiber electrodes may lose muscle-fiber stability for a contraction exceeding 30 percent of maximal voluntary contraction. 23 On the other hand, inaccuracies in recording peak tensions among slow-twitch units may occur because those units generate very little force. Despite these technical limitations, refined microstimulation applied to motor points has enabled researchers to describe the same motor unit types for human muscle as described from animal studies The values noted for properties of human motor units in Table 3 show a broad range. How these a Twitch contraction time (msec). b Fatigue index. Cat Medial gastrocnemius 35 + < > >0.75 Table 1 Tibialis posterior 30 + < > > ,15 Lateral gastrocnemius <40 + < >0.75 >40 > Tibialis anterior 30 + < > > ,16 Extensor digitorum longus 30 + < > > ,16 Flexor digitorum longus < > > st lumbrical <20 + <0.25 <20 + >0.75 < >20 > Rat Tibialis anterior 11.2 < X) FF FR Fint S Source Muscle TCT a SAG Fl b TCT a SAG Fl b TCT a SAG Fl b TCT a SAG Fl b (ref) TABLE 2 Physiological Properties of Typed Mammalian Muscle Units Volume 62 / Number 12, December

4 Muscle (Motor Unit Group) Medial gastrocnemius Tibialis anterior Extensor digitorum brevis 1 st dorsal interosseous Abductor digiti minimi FF FR S FF FR S TABLE 3 Physiological Properties of Human Motor Units a Twitch Contraction Time (msec) > <70 < a Adapted from Grimby and Hannerz. 75 Average Twitch Tension (gm) Axonal Conduction Velocity (m/sec) Fatigue Index <0.63 >0.82 >0.84 <1 1 1 Source (ref) , values relate to specific physiological characteristics of human motor units is uncertain, primarily because of the limited amount of available data. However, the recordings made from 18 medial gastrocnemius muscle units by Garnett and colleagues indicate that type S units have contraction times that are greater than 100 msec and produce peak twitch tensions of less than 10 g. 24 Type FF units contract within 80 msec and produce a wide range of peak tensions (from 2 to over 100 g). Thus, the available evidence indicates that a physiological classification of all mammalian motor units according to the mechanical properties of their associated muscle units is likely to continue to be useful. "Normal" human motor units appear to be organized in a manner similar to that of other mammals, but at the present time, reliable data on the physiological properties of human motor units in health and disease are far less abundant than those derived from animal studies. ANATOMICAL PROPERTIES OF MUSCLE UNITS Animal Studies A major breakthrough in our understanding of the anatomical properties of muscle units came with the development of a means of visualizing the muscle fibers of a single muscle unit. This method, known as the glycogen depletion technique, was developed in several labs 28 " 30 but has been most effectively used by Burke et al 2, 8, 31 and Kugelberg et al. 22, 32 It involves repeated activation of a single motor unit from an intracellular penetration of a single motor neuron, 8 from a dissected ventral root filament, 12 or from intramuscular microstimulation 24 thereby causing the muscle fibers innervated to use their stored glycogen. If stimulation is continued according to the appropriate conditions, the innervated muscle fibers will be depleted of their glycogen and later can be visualized using a histochemical stain for glycogen, a process much like the periodic acid-schiff (PAS) reaction. 8, 33 Innervated fibers belonging to the muscle unit will be seen as lightly stained or unstained fibers against a background of fibers that are intensely stained for glycogen and, therefore, belong to other muscle units. An example of the results of such a glycogen depletion experiment is shown in Figure 2. Use of the glycogen depletion method has led to the identification of two major principles in the anatomical organization of single muscle units. The first principle is that the muscle fibers composing a single unit are not grouped, as some previous physiological studies have suggested. The muscle fibers of a single muscle unit are considerably scattered (Fig. 2), and the probability of even two or three fibers lying exactly adjacent to each other is low. 34 That the distribution of muscle fibers in a single muscle unit is scattered also means that any given volume of muscle is occupied by several muscle fibers belonging to muscle units whose "territories" overlap. The second major principle elucidated by the glycogen depletion method is that all of the muscle fibers of a muscle unit have the same histochemical composition. By reaction of histological sections adjacent to those used for the PAS reaction for different enzymes in the metabolic pathways used by skeletal muscle fibers, it was shown that muscle fibers belonging to a single muscle unit contain a uniform histochemical composition. 8, 32 It was shown further that these histochemical profiles correlate well with the physiological type of the muscle unit. Fast-twitch units (types FF and FR) innervate muscle fibers that react strongly to alkaline-stable myosin adenosinetriphosphatase (ATPase), and fatigue-resistant units (types FR and S) innervate fibers that react strongly to oxidative enzymes. Type Fint units are presumed to contain muscle fibers that are histochemically between those of type FF and type FR units. The myosin ATPase reaction, if carried out at an optimal acid ph, 35, 36 may also be used to differentiate between 1766 PHYSICAL THERAPY

5 the three fiber types: type I fiber type S unit; type IIb fiber type FF unit; and type IIa fiber type FR (and Fint) unit (Tab. 1). In a recent series of excellent studies, Nemeth and colleagues confirmed those earlier studies, and by using quantitative biochemical techniques for assaying a number of different enzymes in type-identified units, they have shown that the muscle fibers of each muscle unit may contain a unique composition of metabolic enzymes.37, 38 Like the physiological organization of muscle units described above, these two principles of the anatomical organization of muscle units have been shown to be generally accepted. Studies of various muscles in various animals have all shown that the muscle fibers in a single muscle unit are spatially separate from one another, forming a "mosaic" pattern, and that they are all histochemically distinct. In addition to these two major anatomical organizing principles, a third principle is emerging of the structural organization of muscle units. Observations of the patterns of glycogen depleted fibers in published records first led Letbetter to postulate that the muscle fibers of individual muscle units are distributed in a "mosaic," but not throughout the entire muscle.39 Instead, they are organized into different regions, or compartments, within the muscle. Each compartment is supplied by a primary branch of the muscle nerve and contains a unique population of muscle units. Studies of the histochemical composition of different muscles also indicated that the fibertype composition (and thus motor-unit type) is not uniform but differs in different parts of the same muscle, or is "compartmentalized."40"44 Detailed studies of the anatomy, the innervation patterns, and the histochemical profile of a single lateral gastrocnemius (LG) muscle of a cat have also described the organi- zation of muscle units into compartments.8, 33, 36 In these studies it was also postulated that the organization of muscle units into compartments provides an explanation for the histochemical "compartmentalization" of muscles observed by others. All of these studies have emphasized the need for careful consideration of the architecture of muscles. In the LG muscle of a cat, for example, as in nearly all muscles, the muscle fibers course between aponeurotic surfaces of origin and insertion.45 In the case of the LG muscle, the aponeurosis of insertion forms the tendocalcaneus (Fig. 3). The muscle fibers belonging to different muscle units are organized into individual compartments within this scheme, and each compartment is supplied by a primary branch of the whole muscle nerve. The compartments lie in parallel to each other so that the muscle units in different compartments produce the same mechanical effects. A similar anatomical organization of muscles into compartments has been demonstrated in cat hamstring muscles46 and in the calf muscles of squirrel monkeys.47 A compartmentalization of the human LG muscle much like that in other animals is suggested by its nerve branching pattern (Gotto and Wolf, 1981, unpublished observations). Thus, the organizational principle that is emerging is that whole muscles are subdivided into smaller compartments in parallel arrangement in the muscle. Each compartment is a collection of single motor units and is supplied by a primary branch of the muscle nerve. Human Studies Use of the glycogen depletion technique has resulted in extending some of the observations on muscle unit anatomy made in animal studies to human Fig. 2. Results of glycogen depletion of a single muscle unit in cat lateral gastrocnemius muscle.18 A. A photomicrograph of a muscle cross section stained with the PAS reaction, which shows the unstained, depleted muscle fibers of a single, type FF muscle unit. B. A tracing of an entire cross section of the muscle that maps the distribution of depleted fibers. Volume 62 / Number 12, December

6 Fig. 3. The distribution of fibers in a single, type FF muscle unit from cat lateral gastrocnemius muscle is shown relative to the distribution of fibers innervated by different primary branches of the muscle nerve. The series of tracings at the top of the figure shows the distribution of muscle fibers in the unit. The series of tracings at the bottom of the figure shows the distribution of fibers supplied by muscle nerve branches, as indicated in the nerve branch diagram to the right. (S soleus; P plantaris; MG medial gastrocnemius.) In the center is a diagram of a dorsal view of the left triceps surae complex (knee to the right, ankle to the left) that serves as a reference to the locations of the cross sections. Note that the muscle fibers of this motor unit are distributed throughout and restricted to the territory supplied by the lateral gastrocnemius branch of the muscle nerve. All data are adapted from English and Weeks 18 and 33, 36 English and Letbetter. studies. For example, muscle fibers of individual human muscle units have been shown to be spatially separated into a mosaic and to be of the same histochemical type. 24 Also, motor units identified by physiological criteria have been shown to contain muscle fibers with a correlated histochemical profile. Thus, it is thought that human type S motor units contain type I musclefibers;that type FF motor units contain type IIb musclefibers;and, although no direct evidence is available, that type FR (and, presumably, type Fint) units contain type IIa muscle fibers. The anatomical disposition of muscle units with respect to the mechanics of muscles has been studied more in cats than in humans. This has been the case mainly because of the inherent limitations in studying human material with biopsy techniques and, possibly, because of a diminished interest in the use of the microstimulation technique initially developed by 1768 PHYSICAL THERAPY

7 Taylor and Stephens 27 for functional isolation of single muscle units. This technique is postulated to stimulate the axon of a single motor unit and cause orthodromic invasion of all of its terminal branches. As a technique it is not without problems, as has been pointed out in this article and by Garnett and colleagues. 24 However, if some of these problems can be addressed using refined electrode designs in conjunction with signal processing techniques, the study of the spatial distribution of human muscle units might be advanced. Of special interest might be whether both large and small human motor units are organized into compartments in a manner similar to that described from animal studies. FUTURE PERSPECTIVES Histochemical Analyses Within the past decade considerable efforts have been directed toward ascertaining the histochemical, and therefore the muscle unit composition, of many human muscles. For example, it has been clearly demonstrated that most human muscles display a wide variation in type I and II muscle fiber composition. 48 " 50 Histochemical profiles of men and women are similar, with men showing generally larger fiber diameters. Female athletes have a higher percentage than their nonathletic counterparts of slow-twitch oxidative fibers. 51 Furthermore, glycogen content is similar in slow-twitch and fast-twitch muscle at rest, 52 and myosin ATPase activity from human muscles of inactive and active subjects 53 is similar. Age may be associated with increased type I fiber composition, but this change is not associated with decreased muscle enzymatic activity. 54 Most histochemical analyses, however, have centered around changes in fiber-type composition resulting from various forms of exercise. These studies generally indicate that intense physical training can increase the aerobic capacity and composition of human muscle. 55 " 60 Data such as these have created great enthusiasm among clinicians and athletes concerned with improved performance but also can be criticized on several grounds. The duration of such enzymatic and fiber-type "conversions" following cessation of consistent, repetitive training is probably limited, so that the long-range significance of such aerobic and composition changes has not been clarified. The magnitude of the changes, though often statistically significant, has not been considered from the point of view of muscle function and muscle unit recruitment, and therefore the changes may be of questionable functional significance. Another criticism relates to the location from which biopsy samples have been taken. Generally, the samples have been limited to a specific site within the vastus lateralis or gastrocnemius muscles. Recent evidence indicates that repeated biopsies from the same area of muscle will display considerable variability in histochemical 61, 62 profiles, even under sedentary conditions. Whether the compartmentalization of muscle units is indicative of a central organizing principle influencing motor control is not yet apparent. However, the implications of the anatomical disposition of muscle units into compartments may bear strongly on muscle structure and function, from both clinical and basic points of view. If histochemical analyses of human muscle can provide significant and meaningful information, the importance of muscle architecture and muscle unit anatomy must be recognized. Clinical interest in histochemical analyses of muscle has been extensive, but elementary questions that govern basic concepts have not been investigated. Questions now being posed by basic scientists but receiving virtually no attention from clinical investigators include: Do the histochemical and physiological properties of muscle units demonstrate differing organization principles in muscles with vastly different fiber architectures? Is the motor unit composition at the proximal location of a two-joint muscle different from the composition at the distal location? Does a unique relationship exist between motor-unit type and muscle-spindle density within that motor unit territory? Answers to these basic questions could have considerable impact on therapeutic interventions. The manner in which therapeutic exercise of a muscle is conducted might be more justifiably ascertained if, for example, it is shown that in humans, as in cats, 36 the knee flexor component of the gastrocnemius muscle is heavily invested with fast-twitch motor units (type II fibers) and muscle units attaching to the aponeurosis contiguous with the tendocalcaneus (the distal part of the muscle) show a preponderance of slow-twitch (type I fibers). Motor Unit Recruitment From both basic and clinical perspectives uncertainty exists about how motor units are best used during volitional tasks. It is generally believed that motor units are recruited according to the size principle proposed by Henneman and co-workers 63 ; that is, during a progressive contraction, tonic or type S motor units are activated before phasic or fast-twitch motor units. From recordings using percutaneous electrodes in humans, phasic motor units appear to have larger amplitudes and greater discharge frequencies than their tonic counterparts. That they are generally recruited after tonic motor units has been clearly documented, and this recruitment order persists during isotonic as well as isometric contractions 70 and maintained voluntary contractions. 71 A reversal of recruitment order, with phasic motor units activated prior to tonic motor units, has also Volume 62 / Number 12, December

8 been demonstrated. Smith et al have shown that fasttwitch muscle units are activated preferentially over slow-twitch units during rapid paw movements in cats. 72 Other study results showing the use of cat LG muscle units from different compartments during posture and locomotion suggest a certain amount of independent control of some fast-twitch units. 73 Grimby and Hannerz have observed "reversals" among individuals with spinal lesions. 74 Recruitment order can also be reversed by temporary disruption of sensory input, 75 cutaneous electrical stimulation, 76 or using a muscle as a synergist rather than as a prime mover. 77 During prolonged voluntary contraction, tonic motor units are recruited at a constant or reduced level of tension and phasic motor units are recruited at increasing levels of tension. Under this condition, phasic motor units are often observed to "drop out." If, however, a rapidly reversed voluntary contraction is made during a maintained contraction, the recruitment order can be reversed. 78 Although considerable practice is necessary to achieve this reversal under the condition of a rapidly reversed voluntary movement, the occurrence implies that a central programming of motor outflow may also be an important factor in motor unit recruitment. To date, systematic study of alternative recruitment patterns has not been undertaken, and the clinical significance of this phenomenon has yet to be elucidated. Most analyses of single motor unit behavior have been undertaken with "normal" humans. Although aberrant patterns of motor unit discharge rates have been noted among patients with spasticity, 78 tremor, 79 and Huntington's chorea, 80 the clinical importance and the implications of these observations for testing efficacy of pharmacological or physical therapies are not clear. In neurogenic or myogenic pathological conditions, among which a reduction of total motor units or an increase in muscle fiber density of remaining motor units can be observed, it becomes difficult to study features of high threshold (phasic) motor units because normal values for their action potential characteristics are lacking. Debate continues about the relationship between motor unit recruitment and purposeful movement. Muscle tension can increase through two primary mechanisms: recruitment of additional motor units and increase in discharge frequency (rate coding). During weak to moderate tonic voluntary contraction, most participating motor units discharge at about the same rate. Differences in discharge frequency appear only during a phasic contraction or with a strong and sustained contraction. Although evidence for recruitment at both moderate 69 and high tensions 68 has been presented, it appears that recruitment at high contraction levels occurs primarily when subjects are not fatigued. The picture has been further complicated by recent observations that recruitment or rate coding may be a function of the muscle under examination. 81, 82 In humans, for example, the small and predominantly slow-twitch adductor pollicis muscle is incapable of recruiting additional motor units above 50 percent of maximal voluntary contraction, so rate coding must account for force modulation at higher tensions. On the other hand, the large, histochemically mixed biceps brachii muscle is capable of recruiting additional motor units up to 88 percent of maximal voluntary contraction and thus generates considerable force through recruitment rather than rate coding mechanisms. Recent animal studies have shown that considerable rate coding occurs during locomotion in both histochemically mixed muscles, such as vastus lateralis and rectus femoris, and in muscles containing predominantly slow-twitch muscle units, such as vastus intermedins. 83 Data such as these indicate that our knowledge of motor unit contributions to muscle tension is still in its infancy, and the relevance of rate coding and recruitment to motor control has yet to be understood. SUMMARY The basic principles in the anatomical and physiological organization of mammalian muscle units that have been developed from animal studies have broadranging applicability both to further animal studies and to studies of motor units in humans. A number of gaps in our knowledge of muscle unit organization have been identified, especially among human studies, but the potential to fill many of these gaps rapidly is great PHYSICAL THERAPY

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