Role of the primary motor and sensory cortex in precision grasping: a transcranial magnetic stimulation study.

Human precision grip requires precise scaling of the grip force to match the weight and frictional conditions of the object. The ability to produce an accurately scaled grip force prior to lifting an object is thought to be the result of an internal feedforward model. However, relatively little is known about the roles of various brain regions in the control of such precision grip-lift synergies. Here we investigate the role of the primary motor (M1) and sensory (S1) cortices during a grip-lift task using inhibitory transcranial magnetic theta-burst stimulation (TBS). Fifteen healthy individuals received 40 s of either (i) M1 TBS, (ii) S1 TBS or (iii) sham stimulation. Following a 5-min rest, subjects lifted a manipulandum five times using a precision grip or completed a simple reaction time task. Following S1 stimulation, the duration of the pre-load phase was significantly longer than following sham stimulation. Following M1 stimulation, the temporal relationship between changes in grip and load force was altered, with changes in grip force coming to lag behind changes in load force. This result contrasts with that seen in the sham condition where changes in grip force preceded changes in load force. No significant difference was observed in the simple reaction task following either M1 or S1 stimulation. These results further quantify the contribution of the M1 to anticipatory grip-force scaling. In addition, they provide the first evidence for the contribution of S1 to object manipulation, suggesting that sensory information is not necessary for optimal functioning of anticipatory control.

Motor cortex excitability after thalamic infarction.

Transcranial magnetic stimulation was used to map hand muscle representations in the motor cortex of a patient in whom infarction of the sensory thalamus deprived the sensorimotor cortex of sensory input. The threshold for activation of the motor cortex on the affected side was higher and the cortical representational maps of individual muscles were less well defined than those on the normal side. It is concluded that electrophysiological changes in cortical organisation can be demonstrated following withdrawal of, or imbalance in sensory afferent activity to the cerebral cortex in humans.

Meiosis: a prostaglandin response that is not inhibited by aspirin.

Antidromic stimulation of the sensory nerve to the rabbit eye produces pupillary meiosis, supposedly by release of prostaglandins into the aqueous humour. The analogy between this phenomenon and neurogenic inflammation is drawn. It is shown that aspirin and indomethacin, known blockers of prostaglandin synthesis and release, fail to block the meiosis thus produced.

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.

Fatigue of single motor units in human masseter.

The spike-triggered averaging technique was used to determine the time course and extent of fatigue of single motor unit twitches in the human masseter. This is the first report of a fatigue test having been applied to masseter motor units in either animals or humans. The human masseter was found to be comprised predominantly of fast-twitch motor units with a broad spectrum of fatigability. Very few physiological type S units were found, despite histochemical evidence for a substantial population of type I fibers in the masseter. In addition, there was no significant correlation between fatigability and either twitch amplitude or contractile speed in the motor units studied. The latter observations are consistent with the unusual histological features of the masseter. Comparison with other human fatigue data suggests that the extent of fatigue in the present population of masseter motor units after approximately 3,000 activations is similar to that reported for populations of units in first dorsal interosseous and medial gastrocnemius.

Studies of stimulus-evoked responses in single motoneurones in humans.

Surface electromyography (EMG) has been a powerful technique for studying reflex and other stimulus-evoked responses in the human nervous system. However, important additional insights can be gained into the operation of neural circuits by studying the responses of single motor units to various stimuli. In this paper, some of the advantages of single motor unit recording will be canvassed, and some examples of the application to this method to the study of reflex responses to sensory stimuli and brain stimulation will be presented.

Estimating post-synaptic potentials in tonically discharging human motoneurons.

The activity of single motor units in human muscles can be recorded with relative ease, and the spike train of a single motor unit precisely reflects the spike train of the parent motoneurone. This has led to the proposal of a number of methods to estimate stimulus-evoked post-synaptic potentials in human motoneurones. All of these methods rely on manipulating the spike trains of motor units over a number of trials. All are based on a number of assumptions, all have limitations, and none so far have passed the test of a direct comparison of the estimate of the shape of the post-synaptic potential with a direct intracellular measurement of it. These techniques are summarised in this review.

A simple circuit for producing vertical arrays of analogue signals and dot raster displays of nerve and muscle action potentials.

It is often helpful to display analogue signals such as electromyograms, electroencephalograms, nerve action potentials, etc., in a regular vertical array. A special case of this display is the widely-used dot raster. This paper describes a simple circuit which enables up to 31 analogue signals to be thus displayed on an analogue storage oscilloscope screen or X-Y plotter. A modification permits up to 255 trials to be displayed. The same circuit produces a standard, dot raster display from standard pulses representing nerve or muscle cell action potentials.

Threshold depolarization measurements in resting human motoneurones.

Threshold depolarization is defined as the amplitude of the depolarization that will just bring a neurone to its firing threshold. Here, a novel technique is described for the measurement of threshold depolarization in resting human motoneurones. The tibial nerve was stimulated at an intensity that was just sufficient for the resulting Ia afferent volley to activate a single motor unit in the soleus muscle. The same motor unit was then recruited by voluntary activation, and the amplitude of the EPSP elicited by this stimulus was determined by a manner described earlier. The value found for the threshold depolarization was around 5 mV for all 6 motoneurones that were successfully tested.

Quantitative analysis of reflex responses in the averaged surface electromyogram.

The relationship between the averaged surface electromyogram (EMG) and the activity of motoneurones in reflex studies is analysed mathematically. This analysis reveals that, subject to certain conditions being met, the integral of the average of the unrectified EMG is linearly related to the activity of motor units in the muscle. This was tested with experimental data. The activity of 2 motor units, and the surface EMG, were recorded directly in a reflex paradigm. A close match was found between the integral of the average of the unrectified EMG and the summed peristimulus time histograms (PSTHs) of the units' activity. This analysis gives more quantitative measurements of the timing of motoneuronal activity in reflexes than the conventional analysis of the EMG. It also offers the potential for making quantitative measurements of changes in motor unit activity evoked by different stimuli. This analysis avoids the pitfall of the artefactual peaks that can occur in the average of the rectified EMG as a consequence of the full-wave rectification. It is concluded that the integral of the unrectified average offers a valuable adjunct to the conventional analysis in many reflex studies. The analysis can also be applied to quantitative studies of neurograms.

An apparatus for controlled stretch of human jaw-closing muscles.

The design of a special-purpose muscle stretcher for reflex studies of the human jaw-closing muscles is described. The device is based on a servo-controlled electromagnetic vibrator which imposes controlled displacements on the lower jaw. The mechanics of the device keep jaw movements coaxial with the temporomandibular joint during the stretches. The design incorporates important safety features including mechanical stops and electronic cut-outs to protect the jaws from excessive stretches.

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.

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.

Axon reflexes in spinal dorsal roots.

The existence of branching of myelinated dorsal root axons has been shown with electrophysiological techniques. The point at which the axons branch is several mm proximal to the ganglion. This observation may be relevant to the interpretation of studies which use spike-triggered averaging to investigate the pattern and the extent of the distribution of sensory information from primary afferent fibers to second-order neurons.

Climbing fiber lesions disrupt conditioning of the nictitating membrane response in the rabbit.

The pattern of acquisition of the classically conditioned nictitating membrane response was determined in rabbits which had recovered from a surgical lesion of the olivary decussation. In comparison with sham-operated controls, the animals with climbing fiber lesions showed delayed and incomplete conditioning. This observation supports the hypothesis of Marr and Albus that motor learning occurs in the cerebellar cortex when conjunctive inputs arrive along both the mossy and climbing fiber pathways.

Discharge variability and physiological properties of human masseter motor units.

Intramuscular electrodes were used to study discharge variability in motor units of human masseter whose physiological properties were determined using spike-triggered averaging. Subjects voluntarily controlled the mean firing rate of a selected motor unit at 10 Hz for 15 min of continuous activation. Discharge variability was assessed at the beginning and end of this period. In 81% of units, the discharge variability at a mean interspike interval (ISI) of 100 ms increased after 15 min of continuous activity. There was a wide range of discharge variability within the population of masseter units studied, but no significant correlations were found between initial discharge variability and recruitment threshold, twitch tension or time-to-peak tension (TTP). There was, however, a significant correlation between motor unit fatigability and its initial discharge variability. This represents a link between the motoneuron and the functional properties of the muscle fibers in innervates.

Instability of motor unit firing rates during prolonged isometric contractions in human masseter.

The firing patterns of up to 4 concurrently active masseter motor units were studied with intramuscular electrodes during a continuous isometric contraction of 15 min duration, in which the subject maintained the mean firing rate of one selected unit at 10 Hz. With this paradigm the net excitation (i.e. mean firing rate) of one unit in the muscle was controlled. This served as the reference for the functional state of other active units during the prolonged contraction. With the mean firing rate of one unit in the muscle fixed, 58% of other active units showed a slow, statistically-significant change in mean firing rate over the 15 min. The initial firing rate of the units did not influence the change in rate. The original firing rate hierarchy, which in short-term contractions reflects the recruitment order, was altered during the prolonged contraction. The explanation for these differential changes in motoneuron net excitation is not clear; they could be intrinsic to the motoneurons or perhaps mediated by reflex pathways. The selective facilitation or suppression of some motor units with continuous activation means that the original size-structured combination of motor units can be modified during a prolonged contraction.

Changes in corticomotor representations induced by prolonged peripheral nerve stimulation in humans.

OBJECTIVE: Manipulation of afferent input can induce reorganization within the sensorimotor cortex which may have important functional consequences. Here we investigate whether prolonged peripheral nerve stimulation can induce reorganization within the human motor cortex. METHODS: Using transcranial magnetic stimulation, we mapped the scalp representation of the corticospinal projection to hand muscles in 8 normal subjects before and after 2h of simultaneous repetitive electrical stimulation of the ulnar and radial nerves at the wrist. Control mapping experiments were conducted in 6 subjects. RESULTS: Following nerve stimulation, larger motor-evoked potentials were evoked from more scalp sites. The induced changes were most apparent in first dorsal interosseous, but were also seen in other hand muscles. The increases in area of the representational maps were accompanied by changes in the location of the optimal site for evoking responses in first dorsal interosseous, and changes in the centres of gravity of the maps. CONCLUSIONS: Prolonged afferent stimulation induces an increase in excitability of the corticospinal projection. This is accompanied by a significant shift in the centre of gravity of the stimulated muscles which we propose is evidence of a non-uniform expansion in their cortical representation.

Recovery of function after cryosurgical lesions of peripheral nerves in rats.

Unilateral lesions were made in rat sciatic nerves with a cryoprobe at about -65 degrees C. Three months later, recovery of motor and sensory function of the hindlimb had occurred. The compound action potential from the dorsal root indicated that myelinated and unmyelinated fibre groups had regenerated. Cryosurgery may be useful in the long-term blockade of sensory nerves for pain relief.

Cross-talk from other muscles can contaminate EMG signals in reflex studies of the human leg.

The extent of contamination of the whole muscle surface electromyogram (SEMG) was studied using the classical H-reflex preparation of the human leg. SEMG and single motor unit activity were recorded from the soleus and the anterior tibial muscles in response to a low intensity stimulation of the tibial nerve at the popliteal fossa. The SEMGs of individual motor units were established to compare with the whole muscle SEMG in order to determine the presence of the cross-talk. It was shown that the whole muscle SEMG can be contaminated by the activity from the antagonists especially at high stimulation intensities.