Circadian modulation of neuroplasticity in humans and potential therapeutic implications.

Learning, memory, and recovery from various neurological insults occur by a process known as neuroplasticity. Neuroplastic changes occur by a variety of physiological processes that modify central nervous system structure and function. The ability to non-invasively induce neuroplastic change in humans is developing as an exciting new field in neuroscience and may ultimately improve treatment outcomes for those suffering various neurological conditions reliant on neuroplasticity for recovery of function. The induction of neuroplastic changes is influenced by several factors, and do not occur evenly throughout the day, but appear to be under circadian control. This review will discuss the known mechanisms and techniques used to induce neuroplasticity, circadian modulation of neuroplasticity, and will discuss the potential implications of these findings for human neurorehabilitation.

Pallidotomy does not ameliorate abnormal intracortical inhibition in Parkinson's disease.

Motor cortex excitability was assessed in 12 patients with Parkinson's disease (PD) using transcranial magnetic stimulation. Patients were studied when mobile and medicated ("ON") and when immobile after medication withdrawal ("OFF"). Results were compared to eight age-matched and 11 young controls. Cortical excitability was assessed by measurement of resting motor threshold (RMT), intracortical inhibition and cortical silent period duration. In five patients, the studies included assessments following pallidotomy. Cortical excitability was abnormal in patients with PD with reduced RMT in "ON" and "OFF" states, and less effective intracortical inhibition. Pallidotomy did not affect cortical excitability in either "ON" or "OFF" states, indicating that enhanced motor cortex excitability in patients with PD is unaffected by pallidotomy despite clinical improvement in motor scores.

Stretch reflexes in the human masticatory muscles: a brief review and a new functional role.

Stretch reflexes play a vital role in fine-tuning movements and in automatically maintaining posture. This article briefly reviews the operation of the stretch reflex in the human masticatory system. The conventional approach of stretching muscles in an open-loop manner has yielded much valuable information on the operation of this reflex. In particular, it has revealed that stretching the jaw-closing muscles evokes a reflex response with two major components. The short-latency reflex is favoured when stretches are brisk, but slower stretches evoke an additional long-latency component. In the hand muscles, the long-latency response is transcortical: in the masticatory muscles, it is not. In addition to its role in servo-control of muscle length during chewing, the stretch reflex in the jaw-closing muscles maintains the vertical position of the mandible during vigorous head movements such as those that occur during running, jumping, hopping and other vigorous whole-body movements in which the head moves briskly up and down. This is an interesting model system in which to investigate stretch reflexes with natural stimuli under unrestrained, physiological conditions.

Asymmetry of motor cortex excitability during a simple motor task: relationships with handedness and manual performance.

Transcranial magnetic stimulation (TMS) was used to assess the relative contribution of the corticospinal (CS) pathway in activating the first dorsal interosseous (FDI) muscle in each hand of 16 right- (RH) and 16 left-handed (LH) subjects with varied degrees of hand preference. It was hypothesised that asymmetry in corticospinal activation of the two hands may be related to hand preference and interlimb differences in manual performance. Subjects performed isometric index finger abduction at force levels of 0.5 N, 1 N and 2 N while TMS was applied at resting threshold intensity (T), 0.9T, or 0.8T. The amount of contraction-induced facilitation of the muscle evoked potential (MEP) was used as an estimate of corticospinal involvement in the task. Patterns of MEP facilitation in each hand were compared with measures of manual performance (finger tapping speed, Purdue pegboard, maximal FDI strength). Threshold TMS intensities for an MEP in FDI at rest were similar in LH and RH subjects, and did not vary between hands. Facilitation of the MEP with voluntary activation was larger overall on the left side (P<0.05), but the asymmetry was dependent on the degree of lateralisation of hand preference. For subjects with consistent hand preference (either LH or RH), MEP facilitation in active FDI was larger for the left hand. For non-consistent RH subjects, contraction-induced MEP facilitation was larger in the right FDI muscle than the left. Asymmetry of MEP facilitation was not correlated with differences between hands in finger tapping speed or performance in the pegboard task, but was associated with relative differences in FDI strength. MEP facilitation tended to be larger in the stronger FDI muscle of the pair. We conclude that corticospinal involvement in the command for index finger abduction is generally greater when the left hand is used, although in RH subjects the asymmetry is influenced by the degree of lateralisation of hand preference. The corticospinal asymmetry is not related to speed or dexterity of finger movements, but the association with muscle strength suggests that it may be influenced in part by preferential use of one hand for tasks which strengthen the FDI muscle.

Task-dependent control of human masseter muscles from ipsilateral and contralateral motor cortex.

Corticotrigeminal projections to human masseter motoneuron pools were investigated with focal transcranial magnetic stimulation (TMS). Responses in left and right masseter muscles were quantified from the surface electromyogram (EMG) during different biting tasks. During bilateral biting, TMS elicited motor evoked potentials (MEPs) in both masseter muscles. On average, the MEP area in the masseter contralateral to the stimulus was 39% larger than in the ipsilateral muscle, despite comparable pre-stimulus EMG in both muscles. MEPs elicited while subjects attempted unilateral activation of one masseter muscle were compared with those obtained in the same muscle during a bilateral bite at an equivalent EMG level. MEPs in the masseter contralateral to the stimulated hemisphere were significantly smaller during unilateral compared with bilateral biting. There was no significant difference in the size of ipsilateral MEPs during ipsilateral and bilateral biting. We conclude that the corticotrigeminal projections to masseter are bilateral, with a stronger contralateral projection. The command for unilateral biting is associated with a reduced excitability of corticotrigeminal neurons in the contralateral, but not the ipsilateral motor cortex. We suggest that this may be accomplished by reduced activity of a population of corticotrigeminal neurons which branch to innervate both masseter motoneuron pools.

Reduced interhemispheric inhibition in musicians.

In vivo magnetic resonance imaging has revealed that the anterior half of the corpus callosum is larger in musicians trained intensively from an early age than in untrained subjects. The corpus callosum is crucial for the coordination of bimanual motor activity, but neurophysiological correlates of morphological differences in the corpus callosum of musicians are not known. In the present study we have used transcranial magnetic stimulation (TMS) to assess interhemispheric inhibition in six adult professional musicians who began musical training at an early age. Conditioning TMS was applied to the hand area of the motor cortex of one hemisphere, followed 4-16 ms later by a test stimulus applied to the other hemisphere. Tests were performed at rest, and with the first dorsal interosseous muscle contralateral to the conditioning hemisphere voluntarily active. Conditioning TMS in musicians was 29% less effective at reducing the size of the test MEP at rest, and 63% less effective in the active condition, compared with control subjects. We conclude that transcallosal interhemispheric inhibitory circuits activated by TMS are less effective in musicians than in controls.

A comparison of cross-correlation and surface EMG techniques used to quantify motor unit synchronization in humans.

Two methods used to estimate the strength of motor unit (MU) synchronization in a muscle are the direct cross-correlation of MU discharge times, and averaging of the surface electromyogram (SEMG) with respect to discharge of a reference MU. Although indirect, the latter approach has the advantage that a global estimate of MU synchrony can be obtained quickly and easily. The two methods are generally regarded as providing equivalent information on the extent of MU synchronization in a muscle, but this proposition has not previously been tested quantitatively. In the present study, we used both the SEMG technique (189 MUs) and cross-correlation of MU discharge (498 MU pairs) to estimate MU synchrony in 28 first dorsal interosseus (FDI) muscles from 16 subjects. Despite considerable overlap in the identity of MUs used to quantify synchrony with each method, linear regression revealed no significant correlation between the estimates of MU synchronization in FDI muscles obtained with the two techniques (r2= 0.04, n = 28). This discrepancy was not due to insufficient sampling of the MU population with the cross-correlation method, although we found evidence for a non-uniform tendency for synchronous discharge in two of 13 motor units providing sufficient data for the analysis. The most likely explanation for the discrepancy between the estimates of MU synchrony is that methodological problems with the SEMG technique limit its accuracy. These problems are difficult to avoid under normal experimental conditions, and we conclude that the SEMG method is not reliable for quantitative comparisons of MU synchrony between muscles and subjects.

Bilateral cortical control of the human anterior digastric muscles.

Transcranial magnetic stimulation (TCMS) was used to determine the organization of cortical motor projections to the anterior digastric muscles in 12 normal human subjects. Two distinct types of potentials were evoked in anterior digastric with a figure-of-eight coil. A short-latency (3 ms) response appeared bilaterally on the surface electromyogram (EMG), but only ipsilaterally on intramuscular recordings: this was the result of direct stimulation of the ipsilateral trigeminal motor root. Motor evoked potentials (MEPs) were elicited in the anterior digastric muscles at variable onset latencies of around 10 ms by stimulation of scalp areas antero-lateral to the area for the first dorsal interosseous muscle of the hand. These were evoked bilaterally in relaxed anterior digastric muscles in six of the seven subjects. In the other subject, the responses in the relaxed muscle were exclusively ipsilateral. However, when the anterior digastric muscles were contracted, the responses were bilateral in all subjects. TCMS and spike-triggered averaging revealed that the bilateral responses were not due to the branching of axons from individual digastric motoneurones to muscles on each side. Because the digastric motor nucleus may contain separate populations of ipsi- and contralateral projecting motoneurones, it was necessary to study single motor-unit responses to TCMS to demonstrate a bilateral corticobulbar projection. The responses of 17 single motor units in the anterior digastric muscle to TCMS were recorded. All were activated by contralateral stimulation. Approximately 80% were also activated by ipsilateral TCMS, although one well-characterised motor unit was inhibited by ipsilateral TCMS. When bilateral activation was present, the ipsilateral responses were more secure than the contralateral responses, which may indicate an additional interneurone in the pathway to the contralateral motoneurone. The major conclusions from this study are that (1) the cortical representation of the anterior digastric muscle is antero-lateral to hand muscles; (2) the cortical projection to the anterior digastric muscles is bilateral; (3) the corticobulbar projection is stronger contralaterally than ipsilaterally but may involve at least one additional synapse; and (4) anterior digastric motoneurones do not branch to innervate the muscles bilaterally.

Motor cortical control of human masticatory muscles.

The corticotrigeminal projections to masseter and anterior digastric motoneuron pools that are activated by TMS are bilateral, but not symmetrical. This conclusion is supported by whole-muscle data showing larger MEPs in the contralateral muscle with unilateral focal TMS, as well as evidence that TMS stimulation of one hemisphere may produce excitation in a masseter or digastric single motor unit while stimulation of the opposite hemisphere produced inhibition of the same motor unit. The asymmetry is particularly marked for masseter, in which the low-threshold motor units were most commonly excited with contralateral TMS and inhibited with ipsilateral TMS. Spike-triggered averaging of digastric motor unit activity revealed cross-talk in surface EMG recordings from digastric muscles, and no evidence that muscle fibres in both digastric muscles were innervated by a common motor axon. Narrow excitatory peaks in the PSTH of motor unit discharge elicited by TMS in masseter (either hemisphere) and digastric motor units (ipsilateral hemisphere) suggest a direct corticomotoneuronal projection. The contralateral projection to digastric motoneurons may include additional oligosynaptic connections, as judged by the broader peaks in the PSTH with contralateral TMS. The organisation of bilateral corticotrigeminal inputs revealed with TMS suggests that: (a) the contralateral hemisphere provides relatively more of the excitatory input delivered via the fast corticotrigeminal pathway for both masseter and digastric motoneuron pools, and (b) corticotrigeminal projections from either hemisphere are capable of contributing to the voluntary command mediating activation of masseter, and (to a lesser extent) anterior digastric muscles on one side, that is independent of the homologous muscles on the other side.

Hemispheric differences in motor cortex excitability during a simple index finger abduction task in humans.

Transcranial magnetic (TMS) and electrical (TES) stimulation was used to assess the contribution of the corticospinal pathway to activation of the first dorsal interosseous muscle (FDI) in each hand of 16 right-handed subjects. TMS was applied at relaxed threshold intensity while the subject performed isometric index finger abduction at seven force levels [0.5 N to 50% maximal voluntary contraction (MVC)]. In a separate session, TES of equivalent intensity was applied to each hemisphere in 5 of these subjects while they performed the same force-matching protocol. In the resting state, mean threshold intensity for a muscle-evoked potential (MEP) in FDI using TMS was similar for the hemispheres controlling the dominant and nondominant hands. The size of the threshold MEPs in resting FDI after TMS and TES were also similar in each hand. With TMS, contraction-induced facilitation of the MEP in FDI was significantly larger when the nondominant hand was used for index finger abduction. In the pooled data, the nondominant/dominant ratio of MEP areas (normalized to the maximum M wave) ranged from 1. 7 in the weakest contraction (0.5 N) to 1.1 in the strongest (50% MVC). Eight subjects had significant differences between hands in favour of the nondominant hand, whereas in two subjects contraction-induced facilitation of MEPs was larger in the dominant hand. In five subjects for whom detailed motor unit data were available from a previous study, lateral differences in MEP facilitation were positively correlated with differences in FDI motor unit synchronization between hands. With TES, contraction-induced facilitation of the MEP was similar in each hand, suggesting that spinal excitability was equivalent on both sides. For the group of five subjects tested with both stimulation techniques, contraction-induced facilitation of the MEP was significantly larger after TMS than that obtained with TES when the contraction was performed with the nondominant hand, but not when the dominant hand was used to perform the task. We conclude that the extent of corticospinal neuron involvement in the command for simple index finger abduction in right-handed subjects is generally greater when the nondominant hand is used, compared with the same task performed with the dominant hand.

Motor unit discharge and force tremor in skill- and strength-trained individuals.

We examined motor unit (MU) discharge properties (mean interspike interval, ISI, discharge variability, short-term synchronization, common drive) and force tremor in the first dorsal interosseous (FDI) muscle of five musicians (skill-trained), five weight-lifters (strength-trained) and six untrained subjects during low-force isometric abduction of the index finger. Mean MU ISI was slightly shorter in skill-trained subjects than in untrained subjects. Discharge variability of FDI MUs did not differ significantly between groups. The mean strength of MU synchronization (expressed as the frequency of extra synchronous discharges above chance) was different in skill-trained (0.22+/-0.02 s(-1), 162 MU pairs), untrained (0.32+/-0.02 s(-1), 199 MU pairs) and strength-trained subjects (0.44+/-0.03 s(-1), 183 MU pairs). FDI MU synchrony was weak and of equivalent strength in both hands of skill-trained subjects and the dominant (skilled) hand of untrained subjects. The stronger FDI MU synchrony in the non-dominant hand of untrained subjects was equivalent to that found in both hands of strength-trained subjects. The extent of common modulation of firing rates (common drive) was assessed for a subset of MU pairs and was weaker in skill-trained subjects (0.30+/-0.04, n=14) than untrained (0.43+/-0.3, n=14) and strength-trained (0.48+/-0.03, n=21) subjects. Force tremor was quantified for each hand in the same subjects during isometric index finger abduction at target forces of 0.5 N and 3.5 N. Tremor rms amplitude and peak power in the force frequency spectrum were significantly lower in skill-trained subjects than strength-trained subjects with the 3.5-N target force. The peak tremor frequency was similar in the three groups. The relatively more independent discharge of pairs of FDI MUs in skill-trained subjects was not responsible for the reduced tremor amplitudes in these subjects. Correlations between the overall extent of MU synchrony and common drive in FDI muscles and tremor measures obtained during the same experimental session were all non-significant. Differences in the central descending command signals are the most likely explanation for the more independent discharge of FDI MUs in skill-trained hands, while neural or peripheral muscular factors may be responsible for the weaker tremor.

Relationship between motor unit short-term synchronization and common drive in human first dorsal interosseous muscle.

We assessed the strength of motor unit (MU) short-term synchronization and common fluctuations in mean firing rate (common drive) in the same pairs of MUs in order to evaluate whether these features of voluntary MU discharge arise from a common mechanism. Shared, branched-axon inputs, with the most important being widely divergent monosynaptic projections to motoneurons from motor cortical cells, are regarded as the principal determinants of MU short-term synchronization. It is not known to what extent these synaptic inputs are responsible for common drive behaviour of MUs. MU spike trains from 77 pairs of concurrently active MUs in first dorsal interosseous muscle of 17 subjects were discriminated with the high reliability needed for common drive analysis. For each MU pair, the data used for comparison of the two analyses of correlated MU discharge came from a single trial (1-5 min duration) of isometric abduction of the index finger. Linear regression revealed a weak, significant positive correlation between the strength of MU short-term synchronization and the strength of common drive in the MU pairs (r2 = 0.06, P < 0.05, n = 77), which was slightly stronger when MU pairs with broad synchronous peaks (> 20 ms) were excluded (r2 = 0.09, P < 0.05, n = 63). These data suggest that less than 10% of the variation in the strength of common drive exhibited by pairs of MUs could be accounted for by differences in the strength of MU short-term synchronization. These two phenomena are therefore likely to arise predominantly from separate mechanisms. At least under these task conditions, the widely divergent, branched-axon inputs from single corticospinal neurons which are important in the generation of MU short-term synchronization play only a minor role in the production of common drive of MU discharge rates.

Spike-train acquisition, analysis and real-time experimental control using a graphical programming language (LabView).

A solution is described for the acquisition on a personal computer of standard pulses derived from neuronal discharge, measurement of neuronal discharge times, real-time control of stimulus delivery based on specified inter-pulse interval conditions in the neuronal spike train, and on-line display and analysis of the experimental data. The hardware consisted of an Apple Macintosh IIci computer and a plug-in card (National Instruments NB-MIO16) that supports A/D, D/A, digital I/O and timer functions. The software was written in the object-oriented graphical programming language LabView. Essential elements of the source code of the LabView program are presented and explained. The use of the system is demonstrated in an experiment in which the reflex responses to muscle stretch are assessed for a single motor unit in the human masseter muscle.

Limitations of the surface electromyography technique for estimating motor unit synchronization.

Motor unit synchronization was estimated from the surface electromyograms (EMG) of the first dorsal interosseus muscle of human volunteers by a simplified surface-EMG technique (Milner-Brown et al. 1973, 1975). Single motor units were identified from intramuscular recordings and were used to obtain a spike-triggered average of the surface-EMG. The discharge rate of a reference motor unit was controlled at two levels (high and low), and the effect of motor unit activity on the surface-EMG estimate of synchronization was studied in 56 motor units. The surface-EMG estimate of motor unit synchronization was significantly higher when the reference motor unit discharged at the high rate than when it discharged at the low rate. A regression analysis indicated that the synchronization ratio calculated from the surface EMG was significantly correlated with the level of EMG activity in the muscle. Motor unit synchronization was also estimated from surface-EMG measurements that were derived by computer simulation. The simulation permitted manipulation of motor unit activity (discharge rate and recruitment) with a complete absence of synchrony among the units in the pool. The stimulated surface-EMG index was influenced by an artifact associated with signal rectification, and this effect changed non-monotonically with motor unit activity. Furthermore, the increase in the motor unit activity reduced the signal-to-noise ratio of the spike-triggered surface EMG average, and consequently decreased the sensitivity of the surface-EMG index as an estimate of motor unit synchronization. We conclude that the simplified surface-EMG method (Milner-Brown et al. 1973, 1975) does not provide a useful index of motor unit synchronization due to its inability to accurately distinguish the synchronization from methodological effects related to a rectification artifact and variation in the signal-to-noise ratio.

Discharge patterns of tonically firing human motoneurones.

We have attempted to reconcile the different patterns of distribution of interspike intervals that are found in motoneurones made to discharge by intracellular injection of constant current in reduced animal preparations and by voluntary control in human subjects. We recorded long spike trains from single motor units in three human muscles made to discharge at constant mean frequencies with the help of auditory and visual feedback. The distribution of interspike intervals in each spike train was analysed quantitatively. We found that the different pattern of discharge of the human motor units could be accounted for when due allowance was made for the variability of the drive to the human motoneurone which arose because of the feedback process used to maintain the target frequency. A model testing this hypothesis gave results that were qualitatively consistent with the human data.

Reduced motor unit activation of muscle spindles and tendon organs in the immobilized cat hindlimb.

Six weeks of limb immobilization of a healthy muscle (cat tibialis posterior) at a short length resulted in a significant reduction of mean fiber area for all fiber types (I, 71% of control; IIa, 77% of control; IIb, 79% of control), whereas fiber type proportions were unchanged. For motor units, there was a reduction in peak tetanic force (type slow > fast fatigue resistant > fast fatigable); an increase in the twitch-to-tetanus ratio for fast fatigue-resistant and slow units; and no effect on the twitch force, twitch time course, or fatigability. The reduction in peak force was greater than expected because of fiber atrophy in slow units. Immobilization had a minimal effect on muscle spindle afferent (Ia and spindle group II) responses to a ramp-and-hold stretch of the passive muscle. Tendon organ (Ib) afferents had an increased responsiveness to stretch after immobilization but only when the muscle was stretched from a short resting length. However, immobilization reduced the modulation of muscle afferent discharge in response to tetanic contractions of single motor units. The decline in responsiveness of spindles was a result of the reduced tetanic force of motor units. In contrast, tendon organs in immobilized muscle were twice as likely to convey no information on the contraction of a single motor unit and were more likely to be unloaded, suggesting that immobilization caused the functional denervation of some muscle fibers. Thus the responses of muscle spindles and tendon organs in immobilized muscle reflected atrophic changes in extrafusal fibers but did not provide evidence for substantial disturbance of receptor function.

Responses of human masseter motor units to stretch.

1. The reflex responses to stretch were studied in single motor units and the surface electromyogram in human masseter. 2. Controlled stretches of the isometrically contracting jaw-closing muscles evoked short-latency (10-15 ms) and long-latency (35-70 ms) excitatory reflex responses in the masseter surface electromyogram. 3. The majority (65%) of tonically active masseter motor units were excited in both short- and long-latency phases of the reflex. The timing of the stimulus determined whether the unit discharged in the short- or long-latency phase. If a non-tonically active motor unit was recruited by the stimulus, it invariably discharged in the long-latency phase. 4. Although short-latency responses were strongly time-locked to the stimulus, there was very little shortening of interspike intervals (ISIs) in this phase of the reflex. The shortening of ISIs was more prominent and prolonged during the long-latency phase, which explains why this phase produces most of the reflex force changes following the stretch. 5. Within pairs of concurrently active motor units there was a tenfold range in the size of the short-latency response to the same stretch. 6. A substantial proportion (35%) of the twenty-two masseter motor units tested had no statistically significant short-latency reflex response. 7. In contrast to other human muscles, there was no functional connection between a population of Ia afferents and some masseter motoneurons. There are two possible explanations for this result. The short-latency, presumably monosynaptic, Ia afferent inputs may not be uniformly distributed to human masseter motoneurons. Alternatively, these inputs may be subject to tonic presynaptic inhibition that is not uniformly distributed throughout the masseter motoneuron pool.

Influence of handedness on motor unit discharge properties and force tremor.

Discharge properties of motor units (MUs) in the first dorsal interosseous muscle (FDI) were studied in the dominant and non-dominant hands of six right-handed (RH) and six left-handed (LH) individuals. MU discharge rates and variability were similar in each hand in RH (186 MUs) and LH (160 MUs) subjects. MU synchronization was less prominent in the dominant hand of RH subjects, with 51% (45/88) of cross-correlograms of MU discharge having significant central peaks, compared with 81% (90/111) for the non-dominant hand. The strength of MU synchronization (expressed as the frequency of extra synchronous discharges above chance) was weaker in the dominant hand of right-handers (0.23 +/- 0.03 s-1 vs 0.39 +/- 0.03 s-1), and synchronous peaks from that hand were slightly broader. Four of six RH subjects had significant differences in synchronization between hands (weaker in dominant hand). In contrast, left-handers had similar incidence (80 vs 82%, n = 161) and strength (0.41 +/- 0.03 s-1 vs 0.37 +/- 0.03 s-1) of MU synchrony in dominant and non-dominant hands. No LH subject had a significant difference in synchronization between hands. Force tremor was quantified in each hand in the same subjects during isometric abduction of FDI at 0.5 N and 3.5 N, and directly correlated with the extent of MU synchronization in the muscle. Tremor root mean square amplitude was similar in dominant and non-dominant hands. Power spectral analysis of the tremor force revealed that the peak frequency in the power spectrum was not influenced by handedness, but power at the peak frequency was higher in the non-dominant hand of RH subjects. Correlations between MU discharge variability and synchrony with measures of tremor amplitude were weak. The reduced MU synchronization in the dominant hand of right-handers may reflect a more restricted distribution of direct projections from motor cortical neurons within the FDI motoneuron pool, or reduced excitability of the cortical neurons during the task. These differences in MU synchronization, however, had an insignificant influence on the magnitude of physiological tremor in the FDI.

Fatigue of jaw muscles and speech mechanisms.

Histochemical studies show that the distribution of fiber types in human jaw muscles is different from that in various limb muscles, no doubt representing different functional demands as well as a different embryological derivation. Jaw-closing muscles appear more resistant to fatigue than limb muscles with intermittent maximal contractions. Endurance of continuous isometric biting is limited by pain. Masseter motor unit fatigability in sub-maximal contractions is similar to the limb muscles. There are few physiological data for the jaw-opening muscles. The distribution of fiber types in human speech muscles is consistent with the high speeds of contraction that must be used in phonation. Although clinical syndromes of fatigue of speech muscles are recognized, there is little direct information on the fatigability of the muscle fibers themselves.

A new approach to the estimation of post-synaptic potentials in human motoneurones.

A new method is described for estimating the shape of the compound post-synaptic potentials evoked by stimuli in human motoneurones. The method is based on changes in the duration of the interspike intervals in motor-unit spike trains that are time-locked to the stimulus. This is particularly helpful in estimating the profile of long-latency slow rise-time post-synaptic potentials that are difficult to estimate with other methods. The method is simple to apply and the analysis is readily implemented on a personal computer.