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A simple electrophysiological method is described for detecting weaknes of psychiatric origin. The method involves the interpolation of a single indirect stimulus to a muscle during the course of a supposedly maximal voluntary contraction. Incomplete motor activation is revealed by the presence of a twitch superimposed on the recording of voluntary torque. [ABSTRACT FROM AUTHOR]

Presynaptic inhibition is a very powerful inhibitory mechanism and, despite many detailed studies, its purpose is still only partially understood. One accepted function is that, by reducing afferent inflow to the spinal cord and brainstem, the tonic level of presynaptic inhibition prevents sensory systems from being overloaded. A corollary of this function is that much of the incoming sensory data from peripheral receptors must be redundant, and this conclusion is reinforced by observations on patients with sensory neuropathies or congenital obstetric palsy in whom normal sensation may be preserved despite loss of sensory fibers. The modulation of incoming signals by presynaptic inhibition has a further function in operating a "gate" in the dorsal horn, thereby determining whether peripheral stimuli are likely to be perceived as painful. On the motor side, the finding that even minimal voluntary movement of a single toe is associated with widespread inhibition in the lumbosacral cord points to another function for presynaptic inhibition: to prevent reflex perturbations from interfering with motor commands. This last function, together with the normal suppression of muscle and cutaneous reflex activity at rest, is consistent with Hughlings Jackson's concept of evolving neural hierarchies, with each level inhibiting the one below it., (Copyright © 2016 the American Physiological Society.)

Transcranial magnetic stimulation (TMS) was first found to be effective in acute migraine 12 years ago, and subsequent studies have confirmed this benefit in approximately two -thirds of treated patients. High response rate, ease of application, and freedom from adverse effects combine to make TMS a natural front-line treatment for migraine, and its use should therefore be encouraged. In relation to the pathogenesis of migraine, the prompt relief of symptoms often observed with TMS is considered incompatible with an underlying neuroinflammatory process and with spreading depression as a cause of aura. Instead, the available evidence points to hyperexcitability of cortical neurons as the immediate cause of headache and any associated symptoms, although the factor(s) leading up to the hyperexcitability remain unclear.

The scintillating zigzag pattern that a migraine patient may see as an illusion before the onset of headache offers a unique investigative approach to visual mechanisms. The likeliest interpretation of these zigzags is that they are the spontaneous discharges of the orientation-selective neurons first described in the striate cortex by Hubel and Wiesel (Hubel DH, Wiesel TN. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J Physiol (Lond). 1962 Jan;160:106-54; and Hubel DH, Wiesel TN. Receptive fields and functional architecture of monkey striate cortex. J Physiol (London). 1968 Mar;195(1):215-43). Although these cells appear to lie in rows in V1, as Hubel and Wiesel found, very few angles in the visual field are represented; this, and the coarseness of the representation, makes it unlikely that the cells act as feature detectors. The orientation-selective cells could, however, monitor the amount of light falling on the retina and thereby enable color constancy to be achieved. The cells may also serve as coarse movement detectors. The new model of cell organization in human V1 enables us to determine the approximate sizes of the receptive fields of the orientation-selective cells.

New evidence concerning the pathophysiology of migraine has come from the results of therapeutic transcranial magnetic stimulation (tTMS). The instantaneous responses to single pulses applied during the aura or headache phase, together with a number of other observations, make it unlikely that cortical spreading depression is involved in migraine. tTMS is considered to act by abolishing abnormal impulse activity in cortical pyramidal neurons and a suggestion is made as to how this activity could arise.

Despite a wealth of information, it is still not known how neurones in the different neocortical layers interact to produce a conscious perception. We now put forward a model for the somatosensory cortex in which a touch is perceived whenever superficial cortical pyramidal cells (in layers II and III) are made to discharge by a recurrent input from deep pyramidal neurones (in layer V). The superficial cells act as biological amplifiers and the number discharging will depend both on the strength of the message from the thalamus and on the variable background depolarisation of their apical dendrites. The recurrent volley arises in the layer V neurones at the end of an IPSP (inhibitory postsynaptic potential), which itself follows an excitatory response induced by the incoming thalamic signal; the IPSP is generated by local basket cells. The duration of the initial excitation--IPSP--late excitation sequence corresponds to a time chunk, that is, the period over which neural activity is integrated to produce a perception. During the time chunk, the superficial cortical pyramids, unlike the deeper ones, can accumulate information as subthreshold excitatory postsynaptic potentials (EPSPs). The relative time at which the information arrived in the cortex is roughly coded by the gradient of EPSPs among cells in an axis perpendicular to the cortical surface. Although developed for the somatosensory cortex, the basic features of the model may well apply to other sensory receiving areas of the cortex.

Motor unit number estimation (MUNE) was shown to be useful in assessing the neurophysiological status of 18 subjects with congenital brachial palsy. This was especially so since conventional M-wave measurements may give misleading impressions as to the extent of motor axon regeneration. In most subjects the involvement of sensory nerve fibers indicated that the traumatic lesions included postganglionic segments of the fibers, with or without preganglionic damage. In a minority the lesions were purely preganglionic. Digital sensory nerve involvement was more in a mediolateral direction, consistent with greater damage to the uppermost elements in the brachial plexus. In 5 individuals, MUNE and sensory testing showed that there had been trauma to the supposedly unaffected arm. Discrepancies between sensory and motor results suggested that reinnervation of the biceps brachii muscle was greater than that of the intrinsic muscles of the hand. In one subject examined serially, reinnervation of the hand muscles was detected by 10 months and continued in the hypothenar muscles for the next 6 years.

Microelectrode recordings have enabled several maps of the body surface to be recognized in the mammalian somatosensory cortex. The maps appear to represent increasingly complex levels of analysis of the sensory message. At present the prevailing opinion is that the different components of the ERPs (event related potentials) represent sequential steps in such an analysis, and such an interpretation is supported by the enhancement of the ERPs when attention is paid to a somatic stimulus. However, there are a number of critical observations which are inconsistent with this view and suggest that the ERP enhancement may be an epiphenomenon. An alternative explanation for the ERPs is that they reflect discharges from the non-specific thalamic nuclei, and are essentially similar to the long latency responses which can be recorded from the cortex during sleep or anaesthesia. Lastly, a hypothesis is proposed for the neuronal events in the somatosensory cortex which culminate in a conscious perception. In this "RULER" model, the deep pyramidal neurones read out the sensory information which has been retained in the apical dendrites of more superficial cells, and do so at the end of successive "time-chunks".

Structure and function are reviewed in the masticatory muscles and in the muscles of the lower face and tongue. The enormous strength of jaw closure is in large part due to the pinnated arrangement of the muscle fibres in the masseter. This muscle, like other masticatory muscles, is unusual in that the cell bodies of the muscle spindle afferents lie in the brain stem rather than in an external ganglion; spindles are absent in the lower facial muscles. Although few data are available, the numbers of motor units in the masticatory muscles, and probably in the lower facial muscles also, appear to be much greater than in limb muscles. The motor units in the facial and tongue muscles are largely composed of histochemical type II ('fast-twitch') fibres, but in the masticatory muscles there are substantial numbers of fibres intermediate between type I ('slow twitch') and type II, and fibre type grouping is present. In comparison with limb muscles, there is little information on ageing changes in oro-facial muscles. The masticatory muscles do, however, show some atrophy and loss of X-ray density, while motor unit twitches are prolonged. Strength is reduced in the tongue and masticatory muscles. It is known that limb muscle properties are largely governed by their innervation, both through the pattern and amount of impulse activity, and the delivery of trophic messengers; the situation for oro-facial muscles is unclear. The structural and functional differences between the two types of muscle indicate the need for conducting ageing studies on the oro-facial muscles, rather than relying on extrapolations from limb muscles.

Motor unit number estimation was employed to assess muscle innervation in 76 patients with prior poliomyelitis. Of the 68 patients who were < 70 years of age, new musculoskeletal symptoms had appeared in all but four; the mean latent interval was 38.0 +/- 10.1 years. As expected, there was a high incidence of muscles exhibiting denervation in previously affected limbs (87%). However, the incidence in supposedly unaffected limbs was also high (65%). Significant differences in the degree of denervation were found between muscles of the same hands and feet. Judged on the basis of their potential amplitudes, the surviving motor units in partially denervated muscles tended to be enlarged. The enlargement was proportional to the extent of the denervation and was comparable to that found in amyotrophic lateral sclerosis. In some muscles, possibly those innervated by failing motor neurons, motor-unit enlargement was not present. Needle examination confirmed the high incidences of denervation in affected and allegedly unaffected limbs. Of the 188 muscles with EMG features of chronic denervation, only nine exhibited fibrillations or positive sharp waves (4.8%). Ninety-five muscles of 18 patients were studied a second time after an interval of 2 years. Overall, there was a 13.4% reduction in motor-unit number and a 18.4% diminution in M-wave amplitude (P < 0.001). The rate of motor-unit loss was twice that occurring in healthy subjects aged > 60 years. Analysis of individual patients indicated that some were deteriorating more rapidly than others. These studies confirm that denervation progresses in patients with prior poliomyelitis in both clinically affected and unaffected muscles, and indicate that this progression is more rapid than that occurring in normal ageing.

In human volunteers, lateral gastrocnemius muscles were stimulated electrically under ischemic conditions so as to produce fatigue. Recordings of electromyographic (EMG) activity were then made from those muscles and simultaneously from untreated medial gastrocnemius muscles during maximal voluntary efforts. In the lateral gastrocnemius the mean amount of EMG activity declined by 52% and was associated with a 35% reduction in the mean amplitude of the M wave (muscle compound action potential) and an insignificant change in M-wave area. In the medial gastrocnemius the EMG was also diminished, by 29%, but there were no significant changes in M-wave amplitude or area. The findings in the medial gastrocnemius are consistent with the existence of an inhibitory reflex effect which originates in the fatigued lateral gastrocnemius muscle and serves to depress excitation in motoneurons supplying that muscle and also in those innervating synergists. The inhibitory effect appears to be long-lasting, in that a significant reduction of the EMG could still be demonstrated 10 min after release of the arterial cuff.

1. Changes in muscle excitation and in isometric twitch force have been studied for up to 8 h after fatiguing stimulation of the human biceps brachii. 2. Within 10 s of a cessation of the 20 Hz fatiguing tetanus, the amplitudes of the M waves (muscle compound action potentials) had returned to control values, whereas the twitch forces were reduced in all subjects. The M waves then decreased in amplitude over the next 3 h, reaching a mean value that was 42.4 +/- 18.6% of control levels (means +/- S.E.M.; P < 0.001). 3. By 8 h, the mean M wave amplitude had recovered to 93.8 +/- 33.3% of control levels, while the corresponding mean twitch force was 104.1 +/- 36.9%. 4. The cellular mechanism responsible for the depression of the M wave is presently unknown, but it is likely to be postsynaptic and may involve Na+ channels.

A simple but effective method has been devised to explore backward masking in cutaneous sensation. In this method a weak electrical shock to the palm (test stimulus) is followed by a stronger shock to the same site (masking stimulus). By combining this stimulation strategy with a choice reaction time paradigm, it has been possible to show that the nervous system responds to the test stimuli even though they are not consciously perceived. Further, the distribution of errors in the different types of trial suggests that, under these experimental conditions, the identification of the stimulus and the choice of response may also be made at a non-conscious level. A tentative scheme for the timing of the various neural events is proposed.

1. The effects of repeated excitation on the compound action potential, or M wave, of mammalian muscle fibres have been investigated in the human biceps brachii. 2. During continuous indirect stimulation at 10 and 20 Hz the mean voltage-time area of the M wave doubled within the first minute, while the mean peak-to-peak amplitude increased by approximately half. The enlargement of the M wave was sustained during stimulation at 10 Hz but not at 20 Hz. Stimulation at 3 Hz caused a small increase which was significant for M wave amplitude only. 3. When the 20 Hz stimulation was performed under ischaemic conditions, the M wave first enlarged and then gradually declined. After 20 Hz stimulation was discontinued, the M wave increased in size; in the ischaemic experiments the release of the cuff produced a further, rapid augmentation. In both the ischaemic and non-ischaemic experiments, the amplitudes and areas of the M waves during the recovery period became significantly larger than the resting values (range, 15-60% at the endplate zone). 4. The mean muscle fibre impulse conduction velocity decreased to less than half the resting value during 20 Hz stimulation, with or without ischaemia, and then increased above the resting value during recovery. 5. On the basis of previous experiments in animals, the augmentation of the M wave was attributed to enhanced electrogenic Na(+)-K+ pumping, and the biceps brachii appeared to be an excellent preparation for studying the time course of this enhancement.

Motor unit estimation in human subjects was conceived in 1967 and was first performed on the extensor digitorum brevis muscle, using a technique of incremental motor nerve stimulation. Losses of motor units were found in elderly control subjects and, surprisingly, in some patients with muscular dystrophy. The pathophysiological basis for the latter observations remains unexplained. Other motor unit studies at that time included the first recordings of single motor unit twitches. The recent development of a software programme for motor unit estimation is a significant advance in that it deals with the problem of "alternation" and eliminates subjectivity. Also of importance has been the introduction, by other workers, of alternative ways of sampling motor unit potentials. It is likely that the field will continue to be active and will benefit from the availability of more powerful computers and more stringent software programmes.

The history of motor unit number estimation (MUNE) is given, together with brief descriptions of the various methods presently available. A small muscle of the hand contains about 100 motor units and greater numbers are found in larger muscles; beyond 60 years the numbers begin to decline. In ALS approximately half the motor units cease to function within 6 months of the involvement of the motoneuron pool, while in adult spinal muscular atrophy further loss may not occur over several years. The reduction in MUNE values in myotonic dystrophy remains an enigma, but even more curious are the losses and subsequent recoveries occasionally observed in hyperthyroidism and chronic renal failure; possibly, nontransmitting ("silent") synapses are involved. MUNE may also be used to study CNS problems such as hemiplegia and congenital brachial palsy. The availability of more powerful computers for EMG should lead to advances in MUNE.

Interstitial potassium concentration, [K+], is modulated during muscle activity due to a number of different mechanisms: diffusion and active transport of K+ in combination with water fluxes. The relative significance of the various mechanisms for muscle function is quantified. The effect of interstitial [K+] locally on the single muscle fiber is discussed along with its effect on the cardiovascular and respiratory systems and its role in motor control. It is concluded that K+ may play a significant role in the prevention as well as the development of fatigue.

Brenda Bigland-Ritchie has made seminal contributions to our understanding of skeletal muscle physiology--the energy cost of muscle when it shortens or is forcibly stretched, the relationship between EMG and force, the behavior of single motor units, and above all, the processes underlying neuromuscular fatigue. More than this, she has stimulated inquiry into the search for reflex mechanisms which may serve to balance the activity of the spinal cord with that of the fatiguing muscles. Her use of human volunteers for much of this work is extraordinary, and represents a major strength. Equally important are her well known and widely cited manuscripts. Not only are her findings clearly described and depicted, but every attempt is made to relate her results to the fatigue processes measured in animal or isolated tissue preparations.

Throughout this epilogue, we have emphasized that rapid advances in understanding of neural and muscular aspects of fatigue have occurred since the 1980 London Symposium. However, in each instance of progress, from the single muscle fiber to the forebrain, the application of more precise techniques have raised important new questions. Neuroscientists and muscle physiologists have expanded opportunities for rigorous study of a topic of major scientific and social importance.

Increased fatigability necessarily occurs in every patient with muscle weakness, regardless of whether the latter is due to a central or peripheral neurological disorder. The tendency for disuse to increase fatigability, as a secondary phenomenon, must also be considered; disuse affects both motoneuron recruitment and the biochemical and physiological properties of the muscle fibers. In recent studies impaired recruitment has been observed in postpolio patients, while patients with multiple sclerosis or spinal cord injury have shown, in addition, altered neuromuscular function. Findings are also presented in ALS and the chronic fatigue syndrome. In general, the most dramatic increases in fatigability take place in disorders of the peripheral nervous system and almost any cell component can be incriminated. There is a need to study fatigability systematically in neurology and rehabilitation.

Neuromuscular adaptations probably occur at all levels of the motor pathway, following changes in muscular activity. Adaptations have been mostly investigated in muscle fibers after heavy-resistance and endurance training. In strength training the rapid improvement is due to poorly understood neural factors, with muscle fiber hypertrophy occurring rather later; fiber hyperplasia is probably unimportant. In contrast to other mammals, muscle fibers in humans do not readily change from "slow" to "fast" and vice versa, although there may be a period of plasticity in infancy especially responsive to weightbearing. A proportion of the changes in the fibers, following training, is probably brought about by stretch-activated mechanisms, in which second messengers express immediate early genes and the latter, in turn, promote the transcription of "muscle" genes; other cellular adaptations occur at the level of mRNA translation. In the spinal cord, adaptations following hemiparesis include a loss of functioning motor units. Impaired motor drive occurs not only in organic brain lesions but also after periods of disuse. In persons with amputations, the peripheral nerve stump undergoes degenerative changes; somatosensory cortical evoked responses, following stimulation of the stump, are diminished. It is possible that both sensory and motor cortical representations are increased for neighboring regions of the body.

The possible causes of the transient enlargement of muscle compound action potentials during repetitive stimulation ("pseudofacilitation") are considered. The phenomenon cannot be due to mechanical artefact, while hypersynchronization of the muscle fiber action potentials, the usual explanation, can only make a minor contribution. A more convincing explanation, for which there is now experimental evidence, is that the muscle fibers undergo hyperpolarization, due to the intramuscular release of norepinephrine and consequent stimulation of the electrogenic Na+,K(+)-pump. Defective phosphorylation of the Na+,K(+)-pump is a possible cause of the transient weakness and myotonia in myotonic dystrophy.

The effects of beta-blockade on skeletal muscle excitability and fatiguability during exercise were examined. Ten healthy males (mean age 21.9 +/- 1.1 yr) performed a 4-min fatigue protocol consisting of intermittent isometric voluntary contractions of the knee extensors in one leg. Subjects performed the exercise after treatment with placebo, 100 mg metoprolol, or an equipotent dose of propranolol (60 mg, n = 1; 80 mg, n = 8; 100 mg, n = 1) twice a day for 76 h before testing according to a randomized double-blind design. The evoked twitch torque, maximal voluntary torque, and maximal M-wave amplitude were unaffected by the beta-blockade treatments before fatigue. During the placebo trial, there were significant reductions in the evoked and voluntary torques (77 +/- 15 and 55 +/- 11%, respectively) after the fatigue protocol; however, both the voluntary electromyogram and evoked M waves were well maintained throughout fatigue. The beta-blockade treatments had no significant effect on torque or electromyogram activity over the course of the exercise. Thus, despite evidence for an impairment of dynamic exercise performance with beta 1- and beta 1,2-blockade, there appears to be no effect of these agents on muscle excitability and fatiguability during isometric muscle activity.

The numbers of functioning motor units can be estimated in proximal and distal muscles of human limbs by an electrophysiological technique in which the mean sizes of the motor unit potentials are compared with the maximum M-waves of the same muscles. Although manual methods of estimation have been used successfully in the past, the introduction of automated techniques has brought considerable advantages, including greater objectivity and reduced contamination of the results by "alternation." In healthy subjects, the intrinsic muscles of the hand have approximately 100 motor units each, and the biceps brachii muscle has only slightly more. With advancing age, there is a loss of motor units, which appears to be more pronounced in distal muscles. The motor unit estimating methodology has been found to be of value in the diagnosis and assessment of patients suspected of having muscle denervation. In amyotrophic lateral sclerosis, the mean rate of motor unit loss is swift, whereas in late-onset cases of spinal muscular atrophy, the reduction in the motor unit population does not appear to progress. In only the most rapidly deteriorating cases of post-polio syndrome is it possible to demonstrate further loss of motor units. In all of these denervating disorders, and in peripheral neuropathies, the importance of collateral reinnervation as a compensatory mechanism is emphasized.

A fully automated system is described for estimating the numbers and relative sizes of functioning motor units in proximal and distal muscles of the arm and leg. In this system, a computer controls the motor nerve stimulation, and analyzes the potentials evoked from the muscles; a subprogram searches for instances of "alternation." In 33 healthy volunteers, aged 21 to 56 years, the median-innervated thenar muscles of one hand were tested 2 to 3 times; the mean motor unit estimate was 228 +/- 93 SD. For similar numbers of biceps brachii, extensor digitorum brevis, and vastus medialis muscles, the respective mean values were 113 +/- 40, 131 +/- 45, and 229 +/- 108 units. The reproducibility of the method was such that the overall coefficient of variation, for the normalized results from the 121 muscles studied, was 22%. The reliability of the automated method was doubled if 3 estimates, rather than one, were performed on each muscle. Comparisons of the results obtained by automated and "manual" methods indicated that the computer-derived values tended to be lower by approximately 33%.

The renewed interest in motor unit estimation (counting) has coincided with the introduction of computer-based methodology and with the application of the technique to proximal as well as distal muscles. The advantages and disadvantages of the different methods are considered, together with the assumptions inherent in this type of examination. In normal subjects, the extensor digitorum brevis (EDB) muscle has approximately 200 motor units while each of the intrinsic muscles of the hand has about 100 units; larger muscles in the limbs contain greater numbers of units. Beyond the age of 60 years, there is a decline in the number of functioning motor units in both proximal and distal muscles. In denervating disorders, motor unit estimation is useful for diagnosis and assessment; abnormal values may often be observed in muscles judged clinically to be unaffected. Serial studies have enabled the rate of motor unit loss to be determined in ALS and in spinal muscular atrophy. Depletion of motor units has also been found following upper motoneuron lesions caused by injury to the spinal cord or by cerebral hemorrhage; trans-synaptic dysfunction has been presumed responsible. Rather surprisingly, reduced numbers of motor units have been observed in a variety of myopathic disorders; of these, the most consistent abnormalities have been reported in myotonic muscular dystrophy.

Maximum M-waves (muscle compound action potentials) were studied in the abductor pollicis brevis (APB), extensor digitorum brevis (EDB), and tibialis anterior (TA) muscles of 12 patients with myotonic muscular dystrophy (MMD) and in the same number of control subjects, matched for age and sex. The peak-to-peak amplitudes and voltage-time areas of the responses were measured at rest, between 40 maximum voluntary contractions (each lasting 3 s) and also during a 2-min recovery period. In 34 of the 36 control muscles the M-waves potentiated during the period of intermittent voluntary contractions. In the MMD patients, however, the M waves exhibited initial declines in 25 of 30 muscles. In the APB and EDB muscles the normalized mean values for the smallest M-waves, recorded during the 350 s total observation periods, differed significantly between the 2 groups of subjects. It is suggested that the sarcolemmal Na(+)-K+ pump has a raised threshold for activation in MMD patients.

1. Human soleus muscles were fatigued under ischaemic conditions by intermittent stimulation at 15 Hz. When maximal voluntary plantarflexion was then attempted, the loss of torque was found to be associated with a reduction in voluntary EMG activity. 2. The decrease in EMG activity could not have been due to 'exhaustion' of descending motor drive in the central nervous system since fatigue had been induced by electrical stimulation of peripheral nerve fibres. Similarly, the decrease could not be explained by changes at the neuromuscular junction or muscle fibre membrane, since changes in the M wave (evoked muscle compound action potential) were relatively modest. 3. When the excitability of the soleus motoneurones was tested during fatigue, using the H (Hoffmann) reflex, it was found to be significantly reduced. Control experiments with ischaemia or electrical stimulation, but without fatigue, failed to demonstrate any significant effects on reflex excitability. 4. The findings in this study favour the concept of reflex inhibition of alpha-motoneurones during fatigue.

The force output of the ankle dorsiflexors was studied during a 40-day simulated ascent of Mt. Everest in a hypobaric chamber; both electrically activated and maximal voluntary contractions (MVCs) were employed. The purpose of this study was to establish whether, under conditions of progressive chronic hypoxia, there was a decrease in muscle force output and/or increased fatigability. We also attempted to identify the main site of any failure, i.e., central nervous system, neuromuscular junction, or muscle fiber. Muscle twitch torque (Pt), tetanic torque (Po), MVC torque, and evoked muscle compound action potential (M wave) were monitored during 205-s exercise periods in five subjects at three simulated altitudes (760, 335, and 282 Torr). All three types of torque measurement were well preserved at the three altitudes. In some subjects, the responses to stimuli interpolated during repeated MVCs provided evidence of "central" fatigue at altitude. In addition, the rate of fatigue during 20-Hz electrical stimulation was greater (P less than 0.01) at altitude and there was increased fatigability of the twitch (P less than 0.025); however, the M wave amplitude was maintained. We conclude that central motor drive becomes more precarious at altitude and is associated with increased muscle fatigue at low excitation frequencies; the latter is the result, in part, of chronic hypoxia and occurs in the muscle fiber interior because no impairment in neuromuscular transmission could be demonstrated.

A combination of electrophysiological techniques, including stimulus threshold measurements, coaxial needle recordings of voluntary EMG, and evoked response analysis, has been used to show that the motor innervation of the human biceps brachii has an extensive distribution in the long axis of the muscle. Impulse collision experiments, involving either excitation at two sites or the use of stimuli of graded intensity, have demonstrated that the diffuse muscle innervation is partly a consequence of individual muscle fibers having more than one end-plate.

Twitch potentiation was studied in human tibialis anterior (TA) and plantarflexor (PF) muscles after maximal voluntary contractions (MVCs). Potentiation was greater in TA and other dorsiflexor (DF) muscles than in PF and was dependent on the intensity of the voluntary effect. It was also observed that potentiation was maximal after MVCs of approximately 10-s duration; after longer voluntary contractions, the potentiation was partially suppressed by fatigue, especially in the TA. Potentiation was significantly larger when muscles were tested in a shortened position regardless of the position at which the preceding MVCs had been performed.

The contractile properties of plantaris and soleus muscles were studied in 46-day-old hamsters after 4 weeks of rear-end suspension; their controls were animals which had not been treated or else had been operated upon but not suspended. In the suspended hamsters the plantaris muscles, of which approximately 90% of fibers are normally type II, maintained the properties of fast-twitch muscles in terms of their contraction and half-relaxation times, maximum rates of rise of tetanic tension, and posttetanic potentiation of the twitch. The small reduction of mean tetanic tension, although not significant statistically, was compatible with relatively mild atrophy of the type II fibers; approximately half of the type I fibers appeared to have converted to type II. In contrast, the soleus muscles, normally slow-twitch with approximately 60% type I fibers, exhibited significant shortening of their contraction and half-relaxation times after suspension and the maximum rates of rise of tetanic tension were increased. These changes, and the greatly reduced twitch and tetanic tensions, were compatible with the finding of much greater atrophy of type I than type II fibers, together with the conversion of approximately 10% of fibers from type I to type II. Unlike other contractile variables, posttetanic depression of the soleus twitch was unaffected by suspension. Our findings have implications in relation to other models of disuse.

Using a combination of single maximal stimuli and maximum voluntary contractions, a comparison has been made of muscle properties in pre- and post-pubertal male subjects. In the dorsiflexor and plantarflexor muscles of the ankle, the twitch and maximum voluntary torques were approximately twice as large in the older subjects; the mean height and mean weight increased by factors of 1.20 and 1.86 respectively. The only other muscle parameter that changed, as a function of age, was the contraction time of the ankle dorsiflexors; the mean value was significantly longer in the older subjects. In the younger subjects, there were already clear differences between the dorsiflexor and plantarflexor muscles, the former developing smaller torques and having shorter contraction and half-relaxation times, greater post-activation potentiation and more susceptibility to fatigue. Even in the youngest subject, motor unit activation was complete in the ankle dorsiflexors; although this was not always true of the plantarflexors, the difference between the two subject groups was not significant.

Recent observations are considered to provide further evidence for an abnormality involving motoneurones in DMD. The dystrophic process appears to take place in two stages of which the first occurs during early embryonic life. This stage is thought to involve faulty inductive actions of the neural tube upon mesoderm and upon itself. The neural consequences vary among individuals and are manifested as mental retardation; EEG abnormalities and losses of functioning motor units. While the first two abnormalities are non-progressive, a further loss of motor units, associated with striking reductions in the numbers of excitable muscle fibers, takes place in trunk and large limb muscles at 9--12 years. The latter process, the cause of which is uncertain, constitutes the second stage of DMD.

Twitch speeds and potentiating capacities have been determined for human medial and lateral gastrocnemius and soleus muscles. The experiments involved and application of submaximal stimuli to the respective muscle bellies, with monitoring of the evoked compound action potentials (M-waves) during repetitive stimulation. Contrary to an earlier report, the lateral gastrocnemius was found to have a significantly shorter mean contraction time (100.0 +/- 10.8 ms) than the soleus (156.5 +/- 14.7 ms) and this value was also significantly different from that of the medial gastrocnemius (113.7 +/- 19.6 ms). The mean half-relaxation time for each muscle also differed significantly from those for the other two muscles. A further contrast between the muscles was that potentiation of the twitch, following a 3-s tetanus at 50 Hz, was significantly greater in the lateral gastrocnemius than in soleus (mean values 60.4 +/- 43.1% and 2.6 +/- 3.3% respectively.

Isometric twitch properties have been compared in two pairs of opposing human limb muscles; these were the brachial biceps and triceps, and the anterior tibial and plantarflexor muscles. All four muscles were examined in each of 24 healthy subjects (16 men and 8 women). The brachial triceps had the shortest contraction and half-relaxation times and the greatest twitch potentiation, while the plantarflexors had the most prolonged twitches and least potentiation; the anterior tibial and brachial biceps muscles had similar characteristics. Susceptibility to fatigue was less in the plantarflexors than in the other three muscles. When muscles were assessed without reference to their anatomical sites, a significant relationship was noted between contraction time and potentiation, but not between either of these features and fatiguability. There was no evidence that muscles were uniformly 'faster' or 'slower' in some subjects than in others.

The possibility of a topographic relationship between the spinal cord and the longitudinal axis of a muscle has been explored in two mammalian hamstring muscles: the rat semitendinosus (ST) and biceps femoris (BF). In both muscles the fibers did not extend the full length of the respective muscle bellies but were arranged in longitudinal arrays. There were two such arrays in BF and three in ST; monopolar recordings revealed that each array had a transverse band of endplates extending across the middle part. By stimulating ventral nerve roots in the lumbosacral outflow, it was found that L5 made the greatest contribution to the innervation of both ST and BF, with lesser inputs coming from adjacent roots. In neither ST or BF was there any evidence of a topographic relationship between the spinal cord and the muscle belly.

The physiological features of two antagonistic muscle groups, the dorsiflexors (DF) and plantarflexors (PF) of the ankle, have been compared in 46 healthy subjects (31 men and 15 women) aged 19-65 years. The DF muscles, of which tibialis anterior (TA) was studied most thoroughly, had relatively small twitches, with moderately fast contraction and relaxation phases, and had marked post-activation potentiation; they were susceptible to fatigue during isometric exercise. The PF muscles had comparatively large twitches, with slow contraction and relaxation phases, and poor post-activation potentiation; they were more resistant to fatigue. Women differed from men in having smaller TA twitches and slower PF twitches; PF twitches were also slower in older subjects. The marked differences in physiological properties between DF and PF muscles contrasted with relatively modest histochemical differences found by ourselves and others.