1Activation of descending corticospinal tracts with transmastoid electrical stimuli has been used to assess changes in the behaviour of motoneurones after voluntary contractions. Stimuli were delivered before and after maximal voluntary isometric contractions (MVCs) of the elbow flexor muscles.
2Following a sustained MVC of the elbow flexors lasting 5–120 s there was an immediate reduction of the response to transmastoid stimulation to about half of the control value. The response recovered to control levels after about 2 min. This was evident even when the size of the responses was adjusted to accommodate changes in the maximal muscle action potential (assessed with supramaximal stimuli at the brachial plexus).
3To determine whether the post-contraction depression required activity in descending motor paths, motoneurones were activated by supramaximal tetanic stimulation of the musculocutaneous nerve for 10 s. This did not depress the response to transmastoid stimulation.
4Following a sustained MVC of 120 s duration, the response to transcranial magnetic stimulation of the motor cortex gradually declined to a minimal level by about 2 min and remained depressed for more than 10 min.
5Additional studies were performed to check that the activation of descending tracts by transmastoid stimulation was likely to involve excitation of direct corticospinal paths. When magnetic cortical stimuli and transmastoid stimuli were timed appropriately, the response to magnetic cortical stimulation could be largely occluded.
6This study describes a novel depression of effectiveness of corticospinal actions on human motoneurones. This depression may involve the corticomotoneuronal synapse.
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During and after voluntary exercise there are changes in the behaviour of the motoneurones and motor cortex. During sustained maximal voluntary isometric contractions, the discharge rate of motoneurones declines from about 30 Hz to below 20 Hz within a minute (e.g. Bigland-Ritchie et al. 1986; Gandevia et al. 1990), and voluntary activation of the muscle also declines as can be demonstrated with motor nerve or motor cortical stimulation (e.g. Gandevia et al. 1996). Thus, the stimuli delivered during the continuing ‘maximal’ effort generate larger force increments from the muscle at the end than at the start of the contraction, that is, central fatigue develops (for reviews see Gandevia et al. 1995; Gandevia, 1998). However, during the contraction the muscle's excitatory response to motor cortical stimulation increases, even when corrected for the increase in size of the maximal compound muscle action potential (Taylor et al. 1996, 1999). After the contraction when the muscle is relaxed, the responses to transcranial magnetic stimulation of the motor cortex are depressed (e.g. Brasil-Neto et al. 1993; Zanette et al. 1995; McKay et al. 1995; Liepert et al. 1996). This post-contraction depression is believed to reflect a purely cortical phenomenon because estimates of the excitability of spinal motoneurones using transcranial electrical stimulation of the cortex were said to be unaltered by the contraction (e.g. Brasil-Neto et al. 1993; cf. McKay et al. 1995).
The present studies were designed to assess the possibility that voluntary contractions induce neural changes at subcortical levels within the motor pathways from cortex to motoneurone. The selected test input was a descending volley excited by electrical stimulation to the cervicomedullary junction via electrodes placed on the mastoids. Based on collision experiments with transcranial electrical stimulation, the transmastoid stimulus is likely to generate a single excitatory volley in corticospinal axons (Ugawa et al. 1991; see also Rothwell et al. 1994). This descending input was also chosen (rather than a reflex input) because corticospinal synapses appear to lack presynaptic inhibition (Nielsen & Petersen, 1994), and thus the response to transmastoid stimulation is likely to reflect only changes in the corticospinal path and motoneurones. To ensure that any changes in the evoked EMG were not due to changes at the muscle fibre membrane or neuromuscular junction (see Cupido et al. 1996), we also recorded responses to supramaximal nerve stimulation. Stimuli were delivered before a sustained isometric maximal contraction and immediately after it. The corticospinal stimuli were deliberately given during muscle relaxation because changes in motoneurone discharge rates with fatigue make it impossible to match the intracellular firing trajectories of motoneurones during voluntary contraction.
The responses to transmastoid stimulation are initially reduced and later facilitated after a voluntary contraction. This initial reduction requires voluntary activity in descending motor paths and is not produced simply by motoneuronal activation. Preliminary findings have been reported (Petersen et al. 1998; Gandevia et al. 1999).
Seven normal volunteers (27–45 years, 3 females) were studied. The procedures were approved by the local ethics committee and the studies conducted according to the Declaration of Helsinki. The subject sat comfortably at a table with the right shoulder flexed and the elbow flexed to 90 deg with the wrist strapped to a rigid myograph which measured elbow flexion torque. The left arm was loosely strapped to a similar apparatus (Fig. 1). Four of the subjects were studied on two or more occasions.
Force and EMG recordings
The isometric force produced by contraction of the right elbow flexors was measured with a linear strain gauge (Xtran). Surface electromyographic activity (EMG) was recorded with electrodes overlying biceps brachii and brachioradialis on the right (fatiguing) side and, in some protocols, from biceps brachii and brachioradialis on the left (non-fatiguing) side. EMG was recorded with surface electrodes (Ag-AgCl discs, 10 mm diameter) firmly stuck to the skin. The subject was earthed via a large flexible strap high on the upper arm. The EMG signals were amplified and filtered (1.6 Hz- 1 kHz).
Recordings were made of the motor responses in the muscles of the upper limb to stimulation at the brachial plexus, electrical stimulation between the mastoids, and magnetic stimulation over the motor cortex.
(1) Brachial plexus stimulation. Single electrical stimuli were delivered with a cathode in the supraclavicular fossa and an anode on the acromion (100 μs duration; Digitimer, DS7, modified to deliver up to 1 A). The electrodes were filled with conductive paste and taped firmly to the skin (Ag-AgCl discs, 10 mm diameter). The intensity of stimulation was set at least 50 % above the level needed to produce a maximal compound muscle action potential (maximal M-wave) in brachioradialis. The average amplitude of the maximal M-waves was 19.2 ± 3.1 mV for recordings from biceps brachii and 14.7 ± 0.9 mV for brachioradialis (mean ±s.e.m.). Because muscles innervated by the musculocutaneous nerve required lower stimulus intensities to produce a maximal response, the final intensity of stimulation for the brachial plexus was usually more than 70 % above that required for a maximal response in biceps. In some studies stimuli were delivered bilaterally.
(2) Cervicomedullary junction stimulation. Single electrical stimuli were delivered via two 9 mm Ag-AgCl electrodes fixed over the left (cathode) and right (anode) mastoid processes and filled with conductive paste (100 μs duration, up to 750 V; Digitimer, D180). The intensity of stimulation of descending motor tracts at the transmastoid level was set with diminishing increments from the stimulator (5 % down to 0.5 % of stimulator output). Responses were monitored at high gain on a dedicated storage oscilloscope (1–2 ms per division), to assess whether the onset latency of responses in the relaxed muscles was reduced markedly (by ∼2 ms) with an increment in stimulus intensity. Such a shift in latency indicated that stimulation was inadvertently occurring along the nerve at or beyond the ventral root rather than at elements presynaptic to the motoneurones. With the subject instructed to relax, the stimulus intensity was adjusted to produce a compound potential in the right brachioradialis of 20–30 % of the maximal M-wave (termed the cervicomedullary motor evoked potential, CMEP). The usual stimulus intensity was ∼500 V. Once this level had been selected, the stimulus intensity was increased to 750 V (the maximal output of the stimulator) to check that a shortening in latency occurred. This confirmed that the selected stimulus for the experiment was below the intensity required to activate the axons of the motoneurones directly. Furthermore, at the selected intensity, the size of the CMEP increased when the subject made a weak voluntary contraction.
(3) Transcranial magnetic stimulation of the motor cortex. Responses (termed motor cortical evoked potentials, MEPs) were evoked by a circular coil (13.5 cm outside diameter) positioned over the vertex (Magstim 200). The output of the stimulator was usually set at 80–90 % maximum. The direction of current flow was set to maximize activation of the left motor cortex.
Care was taken to ensure that no strong contractions were undertaken by the subjects with the upper limbs during the 1–2 h preceding the experimental maximal voluntary contraction (MVC). In the main studies the subjects made a sustained MVC lasting 120 s. Before and shortly after maximal voluntary contractions a ‘set’ of stimuli were delivered. The usual sequence of stimulation in a set is depicted in Fig. 1B. Each set consisted of two stimuli to the cervicomedullary junction, one to the brachial plexus bilaterally, and then two to the motor cortex. Five seconds separated the stimuli and the subject was reminded to relax before every stimulus. Before the MVC, the set of stimuli was repeated three times at intervals of 1–2 min.
The subject received force feedback and constant verbal encouragement during the sustained MVCs. The subject relaxed on instruction and sets of stimuli were begun 5, 35, 65, 95, 120, 150, 210, 300, 420 and 720 s after contraction ceased. An extra transmastoid stimulus was delivered about 2 s after the contraction ended. Apart from the obvious arousal associated with the MVC, care was taken to avoid any unnecessary or unpredictable stimulation which might alter spinal excitability.
Further studies were undertaken to examine the depression of responses to transmastoid stimulation which occurred after voluntary isometric contractions. A short description is given below with further details in Results.
Responses to cervicomedullary and cortical stimulation following MVCs of 5 s duration were studied in four subjects with a similar protocol to that used in the main study. The studies were also conducted in two subjects in whom the duration of the MVC was only 1 s.
Matched MEP and CMEP sizes
In three subjects the stimulus intensities to cervicomedullary and to cortical stimulation were set initially to produce a CMEP and MEP (respectively) of similar size (∼10 % maximal M-wave) in biceps brachii. The duration of the MVC was 2 min. The protocol was otherwise similar to that in the main study except that each set of stimuli consisted of a repeated sequence of cervicomedullary junction, brachial plexus and motor cortex stimulation. After the MVC, stimuli were delivered every 5 s for 270 s with additional sets at 300, 420 and 720 s.
Non-voluntary activation of elbow flexor motoneurones
To determine whether the depression of the response to transmastoid stimulation following MVCs of the elbow flexors required voluntary activation of motoneurones, tetanic contraction of the biceps and brachialis was produced by electrical stimulation of the musculocutaneous nerve. Stimuli were delivered with the cathode over the proximomedial part of the biceps, just below the edge of the deltoid, and with the anode 50 mm distal. The electrodes for musculocutaneous nerve stimulation were Ag-AgCl cups (12 mm diameter) which were covered with gauze and conductive paste. The intensity of stimulation was set to be supramaximal (by 30 %) for a maximal M-wave recorded from the surface electrodes over biceps brachii. The train of stimuli lasted for 10 s and the frequency of stimuli was fixed at 30 Hz (100 μs pulse duration; constant-current stimuli). In a matching study subjects performed a 10 s MVC. The intensity of cervicomedullary stimulation was initially set to produce a response which was about 25 % of the maximal M-wave in the biceps brachii. The sets of test stimuli consisted of two stimuli to the cervicomedullary junction between which a supramaximal stimulus was delivered to the ipsilateral brachial plexus with an interstimulus interval of 5 s. In two of the three subjects the study with the tetanic contraction preceded that with the voluntary contraction by 2 h, and in the third subject the interval between studies was 24 h.
Nature of the descending volley evoked by transmastoid stimulation
In three subjects, we used the protocol of Ugawa et al. (1991) to determine whether the descending volley evoked by transmastoid stimulation was likely to travel in the same axons as those activated by transcranial magnetic stimulation over the motor cortex. The latter stimulus produces a sequence of I-waves and sometimes an initial D-wave in corticospinal axons (e.g. Burke et al. 1993; Nakamura et al. 1997; Di Lazzaro et al. 1998). Subjects were relaxed. We compared the responses to transcranial stimulation, transmastoid stimulation and to both stimuli delivered at several different interstimulus intervals. The stimuli were delivered in blocks for each interstimulus interval, with nine trials consisting of three of each stimulus condition. Based on the study of Ugawa et al. (1991) the intervals were selected to assess whether the initial volley to cortical stimulation should be reduced as a result of collision with the antidromic volley produced by transmastoid stimulation. In the Discussion we argue that the transmastoid shock stimulates corticospinal paths, but prior to that in the text we refer to responses to transmastoid (i.e. cervicomedullary) stimulation.
Analyses and statistics
All responses, including those required to choose stimulus intensities, were acquired with a specialized interface (CED 1401, Cambridge Electronic Design) for later analysis using customized software. Force and EMG signals were sampled at 5 kHz from 50 ms before stimulation to 200 ms after. The size of the responses was assessed using the area of the compound muscle action potential, although measurements of the peak-to-peak amplitude provided the same qualitative conclusions (see Fig. 2). Because some dispersion of the descending volleys reaching the muscle occurs both centrally and in the motor axons with fatiguing contractions (e.g. Taylor et al. 1999), measurements of area were preferred. Area was measured above and below baseline between two cursors set at the onset and end of the potentials. The cursor positions were the same for each type of response throughout a study. The latency of each response was determined by eye aided by a cursor. Similar values were obtained with a computerized algorithm.
Statistical comparisons were made using repeated measures ANOVA with subsequent paired t tests (Student's). Unless otherwise indicated, results are given as means ±s.e.m. Statistical significance was set at the 5 % level.
The maximal voluntary torques for elbow flexion in the male and female subjects were within predicted normal ranges (e.g. Allen et al. 1994). During the sustained maximal voluntary contractions (MVCs) lasting 2 min, maximal torque declined by 65 ± 1 %, whereas it declined minimally for MVCs of 5 s duration. Sets of stimuli to descending motor paths (electrical stimulation between transmastoid electrodes), the motor cortex and the brachial plexus (at Erb's point) were delivered to the relaxed muscles before and after a test maximal contraction. The sets of stimuli were arranged in such a way that the responses to transmastoid stimulation could be corrected for any changes in size of the maximal M-wave (see Methods).
Transmastoid stimulation evoked compound muscle action potentials in the elbow flexor muscles with onset latencies of 7.8 ± 0.2 ms for biceps brachii and 10.2 ± 0.2 ms for brachioradialis. The amplitude of the responses increased during a weak voluntary contraction of the elbow flexors. Such behaviour is consistent with activation of rapidly conducting paths to motoneurones and inconsistent with direct activation of motor axons. The latter possibility was excluded in each study because the response latencies to transmastoid stimulation decreased by about 2 ms if stimulus intensities were increased from the usual stimulus level of ∼500 V to 750 V (see Methods). At the intensities used for the main studies, responses were larger (relative to the maximal M-wave) in biceps than brachioradialis.
Changes in the responses to transmastoid stimulation following muscle contraction
Figure 2 shows typical responses to transmastoid stimulation (i.e. cervicomedullary motor evoked potentials, CMEPs), motor cortical stimulation (i.e. motor cortical evoked potentials, MEPs), and the maximal M-wave. Voluntary contraction of the elbow flexors on one side markedly depressed their responses to transmastoid stimulation. This post-contraction depression of the response to transmastoid stimulation was evident when tested as early as 2–5 s after the contraction and occurred in all subjects. The depression did not occur for the homologous muscles on the non-contracting side (Fig. 2). In contrast, voluntary contraction consistently increased the size of the maximal M-wave in muscles involved in the MVC (Cupido et al. 1996; see also Taylor et al. 1999).
Changes in absolute area of the responses to transmastoid stimulation and those to supramaximal stimulation of the motor nerve are pooled for the group of subjects in Fig. 3. The growth of the M-wave reached its peak about 1–2 min after the contraction and recovered towards the control value after about 7 min. By contrast, the responses to transmastoid stimulation were maximally depressed immediately after the 2 min MVC and recovered to control levels about 2 min after the contraction. The pattern of changes was similar for the biceps and brachioradialis muscles. Because changes in the magnitude of the M-wave must influence the apparent efficacy of responses elicited by transmastoid and motor cortical stimulation, in subsequent analyses we expressed the size of responses relative to the maximal M-wave recorded in the same set of stimuli (see Methods).
To determine whether the size of the depression of the responses to transmastoid stimulation was directly related to the duration of the contraction (and hence the metabolic and cardiorespiratory demands), we measured responses when the duration of the contraction was reduced from 2 min to 5 s (Fig. 4, right panels). In these studies, the first assessment of the responses to transmastoid stimulation occurred 2 s after the contraction ended. Again, the responses were markedly depressed in the motoneurones of biceps and brachioradialis and they recovered to pre-contraction levels with a similar time course to those after MVCs lasting 2 min (Fig. 4, left panels). Additional studies showed that some depression of responses occurred even with contractions lasting 1 s.
One potentially confounding factor was that the absolute size of the initial response to transmastoid stimulation was usually greater than that of the MEP (see below) so that the same motoneurones were not sampled with both descending inputs. However, the post-contraction depression of the CMEP still occurred when the two stimuli activated about the same fraction of the biceps motoneurone pool. An example is shown in Fig. 5.
To examine whether the post-contraction depression of responses to transmastoid stimulation simply depended on activation of the motoneurones rather than descending voluntary inputs to them, we repeated the study but activated the motoneurones using supramaximal tetanic stimulation of the peripheral nerve. In one experiment three subjects made MVCs of 10 s duration, and, in the other, the motor nerve to biceps brachii was stimulated for 10 s at 30 Hz in the same subjects while they made no voluntary effort to contract. Results for both experiments are compared in Fig. 6. As expected from the depression after 5 s MVCs, responses to transmastoid stimulation decreased after the 10 s MVC and did not return to control levels until 2 min after the contraction. However, the responses to transmastoid stimulation showed no depression when the muscle and its motoneurones were activated as a result of tetanic peripheral stimulation at 30 Hz. The simplest explanation is that post-contraction depression of responses to transmastoid stimulation reflects changes in the descending motor pathway at a pre-motoneuronal level (see Discussion).
Apart from the obvious post-contraction depression of the responses to transmastoid stimulation, we noted a small long-lasting facilitation after the 2 min MVC (e.g. Fig. 4). This was also evident after supramaximal stimulation of the motor nerve lasting 10 s (Fig. 6). In the main studies some facilitation also occurred on the non-contracting side (Fig. 2, left panels).
Changes in the responses to transcranial magnetic stimulation of the motor cortex
Following a maximal voluntary effort, the response to stimulation of the motor cortex decreased. However, the reduction had a different time course from that with transmastoid stimulation. After a 2 min MVC, responses were not initially reduced but declined over about 2 min to reach a stable depressed level of 30–40 % of the initial control values (Fig. 7A). This depression was still present 12 min after the contraction. With a 5 s MVC the changes were more variable but there was significant depression over the first 2 min after the contraction (Fig. 7B). Because responses to motor cortical stimulation may be affected by the state of spinal excitability revealed by the responses to transmastoid stimulation, the data have been expressed as a ratio in Fig. 7C. When the changes at a spinal level are taken into account, the responses to motor cortical stimulation are initially markedly increased above control levels but then depressed for many minutes, especially following the longer maximal contractions.
Combined transmastoid and motor cortical stimulation
Transcranial magnetic stimulation activates the corticospinal output particularly to distal muscles of the upper limb (e.g. Palmer & Ashby, 1992). To determine whether the responses to transmastoid stimulation were mediated by the same axons, we delivered cortical stimuli, transmastoid stimuli, and both stimuli at different interstimulus intervals (Fig. 8). Subjects were relaxed. When the cortical stimuli were delivered 0–3 ms before the transmastoid stimuli, the combined response was no larger than that to the transmastoid stimulus alone and its latency was the same as that of the transmastoid response. This interaction was not present when the cortical stimuli were delivered at earlier intervals. The apparent occlusion (at 0–3 ms) is consistent with collision of a descending excitatory volley by an antidromic volley set up by the transmastoid stimulation. If this analysis is correct, the two forms of stimulation are likely to activate a common set of corticospinal axons to elbow flexor motoneurones. Of course, both forms of stimulation may also activate other neural paths.
The main novel finding is that immediately after a sustained voluntary contraction activation of descending motor tracts at the cervicomedullary level by an electrical stimulus delivered between the mastoids produced greatly reduced EMG responses in the muscles which had performed the contraction. This effect recovered within 2 min and was followed by a longer-lasting facilitation of the response. The post-contraction depression was demonstrated in responses that ranged from 5 to 50 % of the maximal M-wave (Figs 2, 4 and 5). The time course of the post-contraction depression was quite different from that produced by transcranial magnetic stimulation of the motor cortex. Before consideration of possible mechanisms for this phenomenon, several technical and measurement issues need to be resolved.
First, what is being activated by the transmastoid stimulation? The study by Ugawa and colleagues (1991) showed that the evoked EMG response to transmastoid stimulation was likely to arise from a single descending volley in corticospinal axons. The strongest evidence for this was the apparent occlusion of the responses to transmastoid stimuli with appropriately timed transcranial electrical stimulation. Our study confirmed this result for the corticospinal output to elbow flexor muscles. Overall, these results suggest that the depression of responses to transmastoid stimuli after a contraction is likely to involve corticospinal axons and their actions on motoneurones.
Second, the way in which EMG responses are quantified in studies of muscle fatigue needs scrutiny. There are variable changes in the maximal M-wave during repetitive stimulation and fatiguing exercise and these may take some time to recover (e.g. Cupido et al. 1996; Taylor et al. 1999). A sustained increase in the size of the maximal M-wave produced by supramaximal stimulation of the brachial plexus at Erb's point occurred after the 2 min MVC and took about 7 min to recover fully. This change did not occur for non-contracting muscles (Taylor et al. 1999; confirmed here). Thus, we usually used a normalization procedure so that the responses to transmastoid stimulation could be assessed in the light of any changes in the maximal M-wave. The depression in the response to transmastoid stimulation after a contraction was evident in raw traces (measured as either peak-to-peak amplitudes or areas; Figs 2, 3 and 5). However, to measure this effect, responses were normalized to the area of the maximal M-wave produced no more than 10 s before or after the transmastoid stimulation. This normalization is likely to be inaccurate in the few seconds immediately after the MVC when the responses to transmastoid stimulation were changing rapidly.
Because the post-contraction depression of responses to transmastoid stimulation was not seen after non-voluntary activation of motoneurones by electrical stimulation of the motor nerve, the depression probably has a premotoneuronal origin. It is likely that the tetanic stimulation will activate early-recruited motoneurones (of low voluntary threshold) trans-synaptically because their conduction velocity will be less than that of the excitatory Ia volley. Motoneurones of higher voluntary threshold will also be activated antidromically. It was not possible to mimic the normal activation of all motoneurones by an artificial form of stimulation. However, the frequency of electrical stimulation matched the mean maximal firing rates of motor units for the biceps during MVCs (Bellemare et al. 1983). Further evidence in favour of a premotoneuronal origin for the depression of responses to transmastoid stimulation comes from the observation that the depression was not influenced by maintenance of the muscle in an ischaemic state (for 2 min) after the contraction, a procedure which will produce sustained activation of its group III and IV afferents (Petersen et al. 1998). If the effect had been mediated by postsynaptic inhibition at a motoneuronal level produced by group III and IV afferents, then the post-contraction depression should not have recovered when the muscle was briefly held ischaemic.
There are at least two possible sites for the depression of responses to transmastoid stimulation. First, the changes may be occurring at corticospinal synapses on motoneurones. The properties of this synapse have been studied in detail in non-human primates (for review see Phillips & Porter, 1968; Porter & Lemon, 1993; see also Lawrence et al. 1985). While we are not aware that single responses have been assessed after a period of repetitive stimulation of the corticospinal system in animals, the EMG responses to single transcranial electrical stimuli are reduced immediately after repetitive magnetic stimulation of the human motor cortex (1 s at 10 Hz) (Modugno et al. 1998). By contrast, responses to transcranial magnetic stimulation were enhanced. Given that the response to weak transcranial electrical stimulation is likely to be dominated by the response to direct excitation of corticospinal axons (D-waves) in awake subjects (Rothwell et al. 1991), the pattern of changes after repetitive cortical activation is similar to that following voluntary contractions. A complex homosynaptic depression with a recovery time course of about 10 s has been described for the Ia afferent motoneurone synapse so that synaptic efficiency of inputs to motoneurones is not necessarily fixed (Hultborn et al. 1996; see also Curtis & Eccles, 1960; Crone & Nielsen, 1989; Lev-Tov & Pinco, 1992). However, a remarkable feature of the post-contraction depression reported here is its duration, which is much longer than that reported for effects at the spindle afferent synapse on human motoneurones.
Second, the absolute size of the evoked descending volley may decline because the excitability of corticospinal axons is reduced due to activity-dependent changes produced by voluntary action. This possibility is hard to assess directly, as it is not possible to record the relevant descending volley. However, an activity-dependent hyperpolarization of peripheral motor axons occurs as a result of voluntary contractions (e.g. Bergmans, 1970; Vagg et al. 1998). Variable changes including increases and decreases in the excitability of single corticospinal axons were reported in monkeys doing voluntary tasks (Schmied & Fetz, 1987). However, there is some evidence that a simple activity-dependent change in axonal behaviour is not responsible for the post-contraction depression, but it is not conclusive. The post-contraction depression of responses to corticospinal stimulation reported here was not directly proportional to the duration of the contraction. Indeed, the depression was surprisingly similar for contractions lasting between 5 and 120 s. In addition, the depression was absent if tested during brief voluntary contractions after the sustained conditioning MVC, rather than at rest as in the present study (Butler et al. 1999).
As expected, we found that responses to transcranial magnetic stimulation of the motor cortex were not depressed immediately after contractions but became depressed and remained depressed for many minutes following sustained fatiguing MVCs (see Introduction and Fig. 7A). The different behaviour of the responses to transmastoid and motor cortical stimulation after contractions not only occurred under the standard testing conditions (e.g. Fig. 2) but also when the initial response to transmastoid stimulation was decreased to match that to motor cortical stimulation. If recruitment of motoneurones by the two forms of stimulation begins with low-threshold motoneurones, then the post-contraction depression of the response to transmastoid stimulation is unlikely to result (for example) from selective inhibition of high-threshold motoneurones. Hence, given our evidence that there may be substantial changes occurring ‘downstream’ of the cell bodies in the motor cortex, the present results highlight the difficulty in interpretation of changes in responses to motor cortical stimulation. The possibility that the corticospinal connection with motoneurones shows large activity-dependent changes following voluntary activity requires further investigation.
This work was supported by the National Health and Medical Research Council of Australia. We are grateful to Drs H. Hultborn and J. Brock for comments on the manuscript and to Drs S. Redman and M. Binder for discussion during the studies.