Impaired response of human motoneurones to corticospinal stimulation after voluntary exercise

Abstract

1. Activation 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. 2. Following 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). 3. To 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. 4. Following 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. 5. Additional 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. 6. This study describes a novel depression of effectiveness of corticospinal actions on human motoneurones. This depression may involve the corticomotoneuronal synapse.

Figure 1. Experimental set-up and the stimulus trains

A, experimental arrangement. Maximal voluntary contractions of the elbow flexor muscles (MVCs) are performed on the right side. Electromyographic responses recorded from over brachioradialis and biceps brachii. Stimuli were applied at supramaximal levels to the brachial plexus at Erb's point. Responses were also evoked by electrical stimulation via electrodes on the mastoid processes. This activates the corticospinal tract (Ugawa et al. 1991). In addition, transcranial magnetic stimulation was delivered over the motor cortex. B, sequence of stimuli used in the main experiments. The interval between stimuli in a set was 5 s. Each set of stimuli was performed prior to the MVC and was repeated at intervals for up to 12 min after the contraction (see Methods).

Figure 2. Typical recordings before and after a sustained MVC of the elbow flexors on the right

Upper panels show the EMG responses from left and right brachioradialis. Lower panels show the EMG responses from left and right biceps brachii. Sets of superimposed responses are shown, first of the control recordings in the pre-exercise period, then from the 30 s immediately after exercise, and finally from the period 5 min after exercise. Following exercise there was a reduction in the size of the response to transmastoid (cervicomedullary) stimulation (CMEP) on the contracting side (arrows) and this had recovered by 5 min after exercise. The response to transcranial magnetic stimulation (MEP) was also depressed following exercise and remained so despite recovery of the response to transmastoid stimulation. Indeed, in this example there was a late increase in size of the response to transmastoid stimulation. No depression of responses occurred on the contralateral (left) side. Note the increase in gain for the responses to transcranial magnetic stimulation. Mmax, maximal M-wave.

Figure 3. Responses to supramaximal stimulation of the motor nerve (M-wave) and to transmastoid stimulation before and after a 2 min MVC

Absolute size of the responses elicited in brachioradialis by supramaximal stimulation of the motor nerve (‘M-wave’, •) and by transmastoid stimulation (i.e. cervicomedullary motor evoked response, ‘CMEP’, ○). The MVC lasted 2 min and is shown by the shaded area. Time ‘zero’ corresponds to the end of the MVC. Means ±s.e.m. for 7 subjects. Following the contraction the M-wave increased above control levels but the response to transmastoid stimulation was depressed. A similar pattern of change was observed for recordings from biceps brachii (not shown).

Figure 4. Grouped data for the responses to transmastoid stimulation before and after MVCs

Upper panels show the normalized responses (CMEPs) from brachioradialis and the lower panels show the responses from biceps brachii. Data for the 2 min MVC on the left and for the 5 s MVC on the right. Because the compound muscle action potential can change as a result of the voluntary contraction, responses to transmastoid stimulation have been normalized to the area of the corresponding maximal M-wave (Mmax) recorded in the same set of stimuli. The shaded region indicates the period of the MVC. Means ±s.e.m. (n= 7). Time ‘zero’ corresponds to the end of the MVC.

Figure 5. Matched responses in biceps with transmastoid and motor cortical stimulation

Responses from one subject in whom the intensity of the transmastoid stimulus was adjusted so that the size of the initial CMEP approximated the size of the MEP produced by motor cortical stimulation (≈5–10 % of the maximal M-wave). Responses are shown (superimposed) for sets of stimuli before and at various times after a sustained MVC of 2 min duration. Immediately after the MVC, the responses to transmastoid stimulation were reduced while those to motor cortical stimulation were initially enhanced and then declined. Note that the largest MEPs occurred immediately after the MVC, when the CMEPs were almost abolished.

Figure 6. Comparison of responses in biceps to transmastoid stimulation after a voluntary contraction and after a tetanic contraction produced by stimulation of its motor nerve

Responses to transmastoid stimulation for 3 subjects after a 10 s MVC (○) and after a 10 s tetanus at 30 Hz (•). Means ±s.e.m. The initial depression of responses to transmastoid stimulation was absent for the tetanic but not the voluntary contraction. This suggests that activation of the motoneurones through peripheral nerve stimulation is not sufficient to depress their responsiveness to a descending volley produced by transmastoid stimulation.

Figure 7. Responses in biceps to transcranial magnetic stimulation of the cortex after MVCs

Responses are shown before and after MVCs of the elbow flexor muscles. Means ±s.e.m. Shaded area denotes the duration of the MVC in each panel. A, subjects (n= 7) performed a 2 min MVC. B, subjects (n= 4) performed a 5 s MVC. C, data for the 2 min MVC (•) and 5 s MVC (○), with the responses to transcranial magnetic stimulation of the cortex expressed as a percentage of the corresponding responses to transmastoid (cervicomedullary) stimulation and normalized to the control values before the contraction. Data for pairs of stimuli have been averaged.

Figure 8. Apparent occlusion of the responses in biceps with combined magnetic cortical and transmastoid stimuli

Responses from a typical recording in one subject for studies in which transcranial magnetic stimuli (Cortex), transmastoid (Transmastoid), and combined stimuli (Both) were applied. Responses were 20–30 % of the maximal M-wave. Each trace is the average of 3 responses. The lowest traces represent the subtraction of the response to transmastoid stimulation from the response to combined stimulation (Both - transmastoid). Vertical dashed lines indicate the timing of the cortical stimulus and the filled arrows indicate the timing of the transmastoid stimulus. When the cortical stimulus preceded the transmastoid stimulus by 4 ms the combined response was slightly facilitated. However, when the interstimulus interval was reduced to 3 ms, there was occlusion, with the response to combined stimulation being similar to the response to transmastoid stimulation alone. Vertical calibration: 2 mV.