Principles of force gradation in skeletal muscles.

A brief survey is given of how motoneurons and motor units are used for the gradation of muscle force during motor behavior. Basic properties of motoneurons and muscle fibers, including major kinds of functional specialization along the axis of 'fast' vs. 'slow', are reviewed. The principles underlying the rate and recruitment gradation of force are described, stressing that the properties of motoneurons and muscle fibers are matched to automate important aspects of the gradation procedure. Recent investigations concerning synaptically evoked changes in the discharge properties of motoneurons receive special attention, including 'plateau' currents and, under appropriate conditions, self-sustained 'plateau' discharges.

Change of required foot impact position during running to exhaustion on a treadmill.

In healthy human subjects running on a treadmill, measurements were made to determine how rapidly and precisely they were able to adjust the impact position of their feet using visual clues. Foot impact position was measured with force transducers at each corner of the treadmill. Required longitudinal positions were indicated by three lines of light ("target-lines"), projected transversely across the treadmill plate. Test runs were conducted until exhaustion at speeds exceeding the aerobic threshold (mean endurance time about 9 min; mean belt speed 12 km/h, mean inclination 6.9 %). During running, required foot positions were, at irregular intervals and during periods of 7 steps each, temporarily switched from the most posterior target-line (TL3) to one of the two more anterior ones (TL2 or TL1). The first change of foot impact position took place within about 175 - 225 ms after a switch from TL3 to TL2/TL1; this initial small change was in a direction opposite to that required. The total adjustment of foot impact position, as seen during 7 consecutive test steps, took place during at least 2 - 3 steps (0.8 - 1.2 s). Towards the end of the test run, with exhaustion approaching, the adjustment process became somewhat slower and showed an increasing lengthwise deficit. Our results demonstrate the existence of prolonged multi-step processes of motor adjustment during treadmill running plus a sensitivity of the foot placement process to time-on-task (when approaching exhaustion?).

Recovery of type I fiber regionalization in gastrocnemius medialis of the rat after reinnervation along original and foreign paths, with and without muscle rotation.

After reinnervation following transection of the sciatic nerve, normal patterns of regional type I fiber distribution are known to return in rat hindlimb muscles. Here we investigate how this recovery is influenced by experimental conditions. In an initial operation, the nerve of gastrocnemius medialis (GM) of adult rats was cut close to the muscle and reinserted either (i) close to the original nerve entry, or (ii) at a more medial 'foreign' site. In other groups of animals, these nerve operations were combined with a rotation of the GM muscle around its longitudinal axis, trying to ascertain whether the position of the muscle within the limb was of importance for the reinnervation processes. In a control group the muscle was rotated but innervation remained intact. After 21 weeks, the GM muscles were removed from both hindlimbs. Cross-sections were cut at seven different levels along each muscle, and 'slow' type I fibers were identified after staining for myofibrillar ATPase. The topographical positions were mapped out for all type I fibers. In all reinnervated muscles, an extensive type I fiber grouping was seen, indicating a widespread respecification of muscle fiber properties by ingrowing 'slow' axons. Normal topographical directions of type I fiber regionalization were about equally well restored in groups with the nerve inserted at the original or at the foreign site. In rotated muscles, the direction of type I fiber regionalization was significantly less rotated than the muscle as a whole. The results suggest that ingrowing 'slow' motor axons are guided toward their normal 'slow' regions by clues which are largely independent of the i.m. path of regeneration (original vs. foreign nerve entry site) but partly dependent on the position of the target muscle within the limb (rotated vs. non-rotated cases).

Bilateral interactions during contractions of intrinsic hand muscles.

During demanding voluntary contractions (e.g., high force or fatigue), activation is not restricted to the target muscle but extends to other ipsilateral muscles; even contralateral muscles become activated. The contralateral "irradiation" of activity was measured in five subjects during submaximal and maximal voluntary contractions (MVCs) of the first dorsal interosseous (FDI) (index finger abduction) and during unfatigued and fatigued conditions. All subjects were tested five times with at least one week between tests. Unilateral MVCs were associated with a substantial amount of contralateral FDI activation [mean = 7.9 +/- 6.7% (SD) MVC prior to fatigue]. The amount of such contralateral irradiation was significantly different between different individuals and was positively correlated between dominant and nondominant hands. During fatigue tests, the contractile activity of the contralateral "nontarget" index finger showed progressive increase (force, electromyogram) as was measured during both the submaximal task and interspersed MVCs of the target finger. In addition, a superimposed saw-tooth pattern of intermittently waxing and waning contractions commonly appeared contralaterally. The expression of contralateral irradiation force was itself fatigue-sensitive: less irradiation was seen in a recently fatigued muscle than was seen before the fatigue test. These fatigue effects could not be explained as having been caused by changes in muscle properties. Possible anatomical sites of contralateral irradiation are briefly discussed.

Quantification of fibre type regionalisation: an analysis of lower hindlimb muscles in the rat.

Newly developed concepts and methods for the quantification of fibre type regionalisation were used for comparison between all muscles traversing the ankle of the rat lower hindlimb (n = 12). For each muscle, cross-sections from the proximodistal midlevel were stained for myofibrillar ATPase and classified as type I ('slow') or II ('fast'). For the 11 'fast' muscles (i.e. all except soleus), the muscle outline and the position of each type I fibre were digitised for further computer processing. Two potentially independent aspects of type I fibre regionalisation were evaluated quantitatively: (1) the degree to which type I fibres were restricted to a limited portion of the total cross-sectional area ('area-regionalisation'): (2) the extent and direction of the difference (if any) between the centre of the muscle cross-section and the calculated centre for the type I fibre cluster ('vector regionalisation'). Statistical analysis showed that type I fibres were vector regionalised in practically all investigated muscles and area regionalised within most of them, the only consistent exceptions being peroneus brevis and peroneus digitorum 4, 5. In muscles with a high degree of area regionalisation the population of type I fibres also had a markedly eccentric intramuscular position (i.e. high vector regionalisation). A significant relationship was observed between the relative position of a muscle within the hindlimb (transverse plane) and the direction and degree of its type I fibre eccentricity. On average, the degree of type I fibre eccentricity was greater for muscles remote from the limb centre than for those situated more centrally. In addition, the intramuscular concentration of type I fibres was typically greatest towards the centre of the limb, the most striking exception being tibialis posterior. For the slow soleus muscle, which is centrally placed within the limb, our analysis concerned the type II fibres, which were found to be weakly vector regionalised but not significantly area regionalised. It is concluded that, within muscles of the rat's lower hindlimb, fibre type regionalisation is a general and graded phenomenon which may reflect differentiating (embryological?) mechanisms of a transmuscular significance. Furthermore, the analysis demonstrated the usefulness of our new methods and concepts for the quantification of fibre type regionalisation.

Fibre type regionalisation in lower hindlimb muscles of rabbit, rat and mouse: a comparative study.

The topographical distribution of different fibre types in muscles of the lower hindlimb in rabbits and mice was quantitatively determined. The results were compared to those previously obtained, using the same new quantification methods, in homologous muscles of the rat. Type I fibres ('slow') were identified using myofibrillar ATPase histochemistry and mapped out at the mid proximo-distal level for 11 'fast' muscles in the rabbit and 7 'fast' muscles in the mouse. For the slow soleus muscle the procedure was undertaken for the type II fibres. Furthermore, for 5 of the 'fast' muscles from each animal species (extensor digitorum longus; flexor digitorum and hallucis longus; gastrocnemius medialis; peroneus longus; tibialis anterior), several more proximal and distal cross-sectional levels were also analysed. All the investigated 'fast' muscles showed a significant degree of topographical eccentricity in the midlevel distribution of type I fibres. For most muscles, the direction of this 'vector regionalisation' of type I fibres was similar between the three animal species. For homologous muscles, the degree of vector regionalisation was significantly different: mouse > rat > rabbit. The relative area of the region containing the type I fibres, inversely related to the degree of 'area regionalisation', was also significantly different: mouse < rat < rabbit. Also within each animal species, muscles with a marked degree of vector regionalisation tended to show a marked area regionalisation. Proximo-distal differences in type I fibre density were observed in all the three species of animals; also these patterns showed marked inter-species differences. The findings demonstrate the general occurrence of, and systematic relationships between, different aspects of type I fibre regionalisation. The observed interspecies differences suggest that the expression of this phenomenon is adapted to differing functional needs.

Simple methods for quantifying the spatial distribution of different categories of motoneuronal nerve endings, using measurements of muscle regionalization.

For skeletal muscles, a well-known match exists between the properties of motoneurones and those of their muscle fibres. Hence, the intramuscular distribution of different kinds of motoneuronal nerve endings (e.g. 'slow' versus 'fast') can be mapped by determining the distribution of the corresponding types of muscle fibre. As a background for further studies of motoneuronal plasticity, we needed precise measures of such distributions. Simple quantitative methods were developed for defining the position and extent of sub-populations of cells within a structure (e.g. the regional distribution of slow versus fast muscle fibres within a muscle cross-section): (a) The 'mass vector method' defined the relative position of the target cell cloud. A line was drawn between the calculated centre of mass for the target cells and that for the whole structure. The direction (a1) and length (a2) of this line gave a measure of the direction and degree of target cell eccentricity within the structure. (b) The 'sector method' delineated the region containing the target fibres. A circle around the centre of mass for the target fibres was subdivided into a number of equal sectors (standard setting: 20). The most remote point was found within each sector and a line joining these points defined the region of the target fibres. When applied to the 'slow' type I fibres of cross-sections from rat hindlimb muscles, the regional area estimates obtained by the sector method were highly correlated with, but approximately 10% lower than those achieved by the well-established 'convex hull' method. Highly significant inter-muscular differences were observed for each one of the three new parameters described in this paper (a1, a2, b).

Neurotrophins and trk-receptors in adult rat spinal motoneurons: differences related to cell size but not to 'slow/fast' specialization.

We have studied the mRNA expression of the neurotrophins brain-derived neurotrophic factor (BDNF), NT-3 and NT-4 and of their receptors trkB and trkC in individual retrogradely labeled lumbar spinal motoneurons of the adult rat, using quantitative non-radioactive in situ hybridization (ISH). We measured soma size and the optical density of the ISH reaction. We analyzed mRNA expression patterns in predominantly 'slow' or 'fast' motoneurons by comparing retrogradely labelled cells that innervated the slow m.soleus (Sol) with those innervating the fast m.extensor digitorum longus (EDL). Within individual motoneuron pools, there was a considerable variation in the intensity of mRNA expression encoding for BDNF, NT-3 and NT-4, as well as for the receptors trkB and trkC. The expression of trkC mRNA was significantly higher in small, presumed fusimotor neurons than in the larger alpha-motoneurons. Surprisingly, none of the variations in the level of motoneuronal mRNA expression for trkB, BDNF, NT-3 and NT-4 were related to soma size and no differences were found between EDL and Sol motoneurons. Apparently, the considerable variations in neurotrophin and neurotrophin receptor mRNA expression represent other parameters of motoneuronal specialization than those related to the well-established 'fast' vs. 'slow' categories of motoneurons.

Potentiating and fatiguing cortical reactions in a voluntary fatigue test of a human hand muscle.

Fatigue-associated changes in the excitability of central motor mechanisms were investigated using transcranial magnetic stimulation (TMS) of the motor cortex. Test stimuli were applied before, during and after a voluntary fatigue test of the first dorsal interosseus muscle (FDI). Subjects were required to maintain 50% of their maximum voluntary force (MVC) for at least 2 min (1/2-MVC test) and electromyographic (EMG) reactions of FDI were measured with surface electrodes. Prior to the test, TMS pulses of 70% maximum output (about 1.4 T) produced muscle-evoked potentials (MEPs) of widely different amplitudes in different subjects, ranging from 13% to 55% of the maximum compound action potential (M-wave) evoked by ulnar nerve stimulation. During the test, MEPs of all subjects showed a potentiation; this effect was markedly greater in subjects with a small initial MEP. After the test, the differential degrees of contraction-evoked potentiation still influenced the MEP amplitudes; small pre-test MEPs showed a post-test net potentiation and larger pre-test MEPs showed a net post-test depression. The results underline that the net outcome of motor activation on motor cortex excitability, as studied with TMS, depends on a complex balance of fatiguing and potentiating effects.

Proximo-distal organization and fibre type regionalization in rat hindlimb muscles.

Five muscles of the rat's lower hindlimb were compared with regard to their histochemical fibre type distribution at seven different proximo-distal levels. The muscles were: extensor digitorum longus (ED), flexor digitorum and hallucis longus (FD), gastrocnemius medialis (GM), peroneus longus (PE) and tibialis anterior (TA). In all the five muscles, the relative density of the 'slow' type I fibres showed a striking and similar decrease from proximal toward more distal levels. In addition, the type I fibres were concentrated within smaller and more eccentrically placed regions at distal than at more proximal levels. As a background for the further analysis of these lengthwise aspects of type I fibre regionalization, architectural features of the muscles were determined. Pinnation angles and the position of major tendons and tendon sheets were assessed in fresh specimens. Muscle fibre lengths were measured for single fibres dissected from different regions of macerated muscles. In all cases, fibre length was much shorter than muscle length (mean fraction ranging from 21 to 55%), implying that the proximo-distal changes in histochemical fibre properties were indeed explainable as being due to gradual lengthwise changes in fibre type populations. The similarity of these lengthwise changes across the muscles was in contrast to their differences in other aspects of functional organization, such as the average density of type I fibres and architectural features determining their relative capacities for shortening and force generation. The possible functional role of the proximal accumulation of type I fibres was discussed in relation to circulation and thermal balance; besides, the proximo-distal regionalization of type I fibres might (partly) reflect processes that had been associated with early stages of muscle differentiation. Furthermore, the results underline that, when determining the fibre type composition of rat hindlimb muscles, identifying the proximo-distal level of sampling is a matter of great importance.

Ragnar Granit 100 years--memories and reflections.

The Swedish-Finnish Nobel laureate Ragnar Granit, born 100 years ago, is commemorated in a brief article by one of his former PhD students and collaborators. After a short account of Granit's life and scientific career, special attention is given to Granit's role as a teacher in research training and his published thoughts on this matter, partly reflecting Granit's own experience as a "postdoc" in the laboratory of Sherrington (Oxford). The article includes personal recollections of how it was to work together with Granit in his laboratory.

Fatigue-associated changes in the electromyogram of the human first dorsal interosseous muscle.

Muscle fatigue is a clinically important symptom, often analyzed using electromyography (EMG). We analyzed fatigue reactions of the first dorsal interosseous muscle (FDI) during a maintained contraction at half-maximal force ((1/2)-MVC test). EMGs were recorded with large surface electrodes and, simultaneously, with intramuscular fine-wire electrodes. Compound muscle action potentials (M waves) were evoked by electrical ulnar nerve stimulation. During the first half of the test, an almost direct proportionality was found between the variations in voluntary rectified and smoothed EMG (rsEMG) and in M-wave area as recorded with surface electrodes. This indicated that much of the variation in voluntary EMG reflected changes in the spike-generating properties of the muscle fibers. The changes in the fatigue-associated rsEMG were often quantitatively markedly different for the "wide-angle" recording from the surface and the more local intramuscular recording. This suggests that fatigue-associated EMG-responses of the FDI have a markedly heterogeneous intramuscular distribution.

Discharge properties of motoneurones: how are they matched to the properties and use of their muscle units?

A general survey is given of old as well as more recent findings concerning matches between electrophysiological properties of motoneurones and contractile properties of their muscle fibres. Mechanisms for creating and maintaining such matches are discussed. It is pointed out that it is not sufficient to describe the variation of functional motoneurone characteristics simply in terms of 'fast' or 'slow': all properties seem continuously graded and there is cytochemical evidence for several, seemingly independent parameters of functional specialisation.

Influence of a voluntary fatigue test on the contralateral homologous muscle in humans?

Influences of a submaximal endurance test in the right first dorsal interosseus on force and fatigue-related parameters of activating the contralateral muscle were studied. The test consisted of a 30% maximum voluntary contraction (MVC), regularly interrupted by maximal contractions and brief rest periods. Despite the induced central fatigue, as tested with the MVC-superimposed twitch technique, and substantial peripheral fatigue, only minor effects of the previous fatigue test were seen for the contralateral hand. No significant influence was found on endurance time, the perceived effort for maintaining 30% MVC force or the MVC-superimposed twitch. Thus, our fatigue protocol induced both central and peripheral fatigue but only minor cross-over effects of fatigue were found for the homologous contralateral muscle.

Relation between fibre composition and daily duration of spontaneous activity in ankle muscles of the cat.

UNLABELLED: This study concerns the relation between use and fibre type composition among limb muscles. The histochemical properties were investigated for ankle muscles from cats that had previously been studied in 24 hr electromyographic (EMG) recordings of daily spontaneous activity. We then reported average daily "duty times" (i.e. the percentage of total sampling time filled with EMG activity) of 1.9% for extensor digitorum longus (EDL), 2.1 and 4.0% for anterior and posterior sites of tibialis anterior (TA), 6.6 and 9.5% for anterior and posterior sites of peroneus longus (PL), and 13.9% for soleus (SOL). In the present experiments, muscles from which these data had been obtained were sectioned in a cryostat and stained for myofibrillar ATPase. Fibres were classified as type I (presumably slow) or II (presumably fast), the latter fibres being further categorized as IIA, IIB and a minor portion of transitional IIAB fibres. As expected, SOL was 100% type I. Among the muscles of mixed fibre-type composition ("mixed muscles"), a statistically significant difference in the mean percentages of type I fibres was found between TA or EDL (2.9-6.0%) vs. PL (11.8-14.6%). For TA the percentage of type I fibres was higher in posterior (deep) than in anterior (superficial) sampling regions; for PL no clear antero-posterior difference was found. A significant correlation was obtained between the percentage of type I fibres and the total duration of daily activity recorded from corresponding mixed muscle sites (5 different recording sites in 4 cats, totally 15 cases of successfully combined physiological and histochemical measurements, r = 0.76, P < 0.001). Similarly, within TA the total duration of daily activity was higher for sites with high (posteriorly) than for those with low (anteriorly) percentages of type I fibres. IN CONCLUSION: a "coarse-grain" relationship was found between fibre type composition and the duration of daily activity among mixed muscles. Possible mechanisms underlying this relationship are discussed.

The final common pathway in postural control--developmental perspective.

A brief review is given concerning postural specialisations among mammalian muscle fibres and motor units. Most skeletal muscles contain a mixture of fibres with different characteristics, and their slow-twitch (S) units are well-known to possess properties suitable for postural tasks: they are highly fatigue-resistant, well equipped for oxidative metabolism, and their slowness makes them energetically cheap in (semi-)isometric contractions. These features are adequately employed in motor behaviour owing to characteristics of the associated motoneurones. In adult mammals, the way in which a muscle is used can influence its proportion of S units. This adjustment occurs within a restricted 'adaptive range' which differs between muscles and animal species, presumably being preset at an early age. In the course of early foetal development, part of the slow vs. fast differentiation of muscle fibre properties can take place independently of innervation. Once innervation has taken place, however, motoneurones influence the differentiation in various ways. On the whole, a well coordinated timing seems to exist between the early differentiation of central motor mechanisms and of the peripheral machinery, largely causing the neuromuscular system to be/become ready for use when the brain needs it.

Task-related variations in motoneuronal drive to a human intrinsic hand muscle.

Maximal electromyogram (EMG) levels of the first dorsal interosseus muscle (FDI) were studied during maximal pinching between index finger and thumb at two different wrist angles. Despite the fact that there was no change in the biomechanical conditions for the FDI, the maximal EMG levels of the FDI differed significantly; typically EMG levels were higher while pinching at a maximally flexed wrist angle compared to a maximally extended wrist angle. The stability of the EMG recordings was checked with supramaximal peripheral nerve stimulation. Significant changes in the area of the compound muscle actions potentials (M-waves) were obtained. However, these changes could not explain the observed differences in the maximal EMG levels. Our results suggest that the ease of producing a maximal drive to the FDI muscle depends on the motor task.

Circadian and individual variations in duration of spontaneous activity among ankle muscles of the cat.

This article concerns the spontaneous motor behavior of cat hindlimb muscles and muscle regions using 24-h electromyographic (EMG) recordings. Previously, we found marked differences in average daily "duty time" (i.e., the percentage of total sampling time filled with EMG activity) between different muscles, or muscle portions. We have now analyzed systematic differences in duty time between (i) highly active (midday) and relatively inactive (midnight) periods, and (ii) individual cats. Differences between cats seemed to be associated with differences in motor habits. The midnight reduction in activity was particularly striking for muscles with a high midday activity. Quantitative differences in spontaneous activity (duty time), as compared between active and inactive periods of the day or among individual cats, were associated with marked qualitative alterations in the distribution of activity among the sampled muscles, i.e., these quantitative differences could not be described as a simple up- or downscaling of general motor activity.