Focal depression of cortical excitability induced by fatiguing muscle contraction: a transcranial magnetic stimulation study

Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the motor cortex were recorded in separate sessions to assess changes in motor cortex excitability after a fatiguing isometric maximal voluntary contraction (MVC) of the right ankle dorsal flexor muscles. Five healthy male subjects, aged 37.4±4.2 years (mean±SE), were seated in a chair equipped with a load cell to measure dorsiflexion force. TMS or TES was delivered over the scalp vertex before and after a fatiguing MVC, which was maintained until force decreased by 50%. MEPs were recorded by surface electrodes placed over quadriceps, hamstrings, tibialis anterior (TA), and soleus muscles bilaterally. M-waves were elicited from the exercised TA by supramaximal electrical stimulation of the peroneal nerve. H-reflex and MVC recovery after fatiguing, sustained MVC were also studied independently in additional sessions. TMS-induced MEPs were significantly reduced for 20 min following MVC, but only in the exercised TA muscle. Comparing TMS and TES mean MEP amplitudes, we found that, over the first 5 min following the fatiguing MVC, they were decreased by about 55% for each. M-wave responses were unchanged. H-reflex amplitude and MVC force recovered within the 1st min following the fatiguing MVC. When neuromuscular fatigue was induced by tetanic motor point stimulation of the TA, TMS-induced MEP amplitudes remained unchanged. These findings suggest that the observed decrease in MEP amplitude represents a focal reduction of cortical excitability following a fatiguing motor task and may be caused by intracortical and/or subcortical inhibitory mechanisms.     

Central fatigue during a long-lasting submaximal contraction of the triceps surae

Our purpose was to study central fatigue and its dependence on peripheral reflex inhibition during a sustained submaximal contraction of the triceps surae. In 11 healthy subjects, superimposed twitches, surface electromyograms (EMG) from the medial head of the gastrocnemius (MG) and soleus (SOL) muscles, maximal compound motor action potentials (M_max), tracking error and tremor were recorded during sustained fatiguing contractions at a torque level corresponding to 30% of maximal voluntary contraction (MVC). When the endurance limit (401±91 s) of the voluntary contraction (VC-I) was reached, the triceps surae could be electrically stimulated to the same torque level for an additional 1 min in 10 of the 11 subjects. These subjects were then able to continue the contraction voluntarily (voluntary contraction II, VC-II) for another 85±48 s. At the endurance limit of VC-I, the superimposed twitch was larger than during the unfatigued MVC, while there was no significant difference between the twitch at the endurance limit of VC-II and MVC. The EMG amplitude of both MG and SOL at the endurance limit of VC-I was significantly less than that during the MVC. While the EMG amplitude of MG increased further during VC-II, SOL EMG remained unchanged, neither muscle reaching their unfatigued MVC values. This difference was diminished for SOL by taking into account its decrease in M_max found during VC-II, and relative EMG levels approached their MVC values. These results clearly indicate that a higher voluntary muscle activation was achievable after 1 min of electrical muscle stimulation, which continued metabolic stress and contractile fatigue processes but allowed for supraspinal, muscle spindle and/or motoneuronal recovery. It is concluded that peripheral reflex inhibition of -motoneurons via small-diameter muscle afferents is of minor significance for the development of the central fatigue that was found to occur during the first voluntary contraction.     

Corticospinal Facilitation Studied During Voluntary Contraction of Human Abdominal Muscles

Transcranial magnetic stimulation (TMS) of the human motor cortex was used to study facilitation of motor-evoked potentials (MEPs) in the rectus abdominis (RA) muscle, a trunk flexor, during voluntary activation. MEPs could be produced in the relaxed RA muscles of all six normal subjects studied. The MEPs had short latencies (18-22 ms) which are consistent with other studies suggesting a fast corticospinal input to the trunk muscles. Marked facilitation was observed in the MEPs when subjects were asked to produce graded levels of voluntary contractions. The two tasks used to produce voluntary contractions were a forced expiration during a breath-holding task (FEBH) and bilateral trunk flexion (BTF). Maximal voluntary EMG activity during the BTF task produced around 4.2 times more integrated EMG than during the FEBH task. Similarly the MEP amplitude at MVC was 2.3 times greater during BTF than FEBH. The pattern of MEP facilitation with increasing voluntary EMG was not linear and a maximal MEP amplitude was observed at a level of voluntary contraction around 30 % MVC in both tasks. There were some subtle differences in the pattern of facilitation in the two tasks. When TMS was applied to the right cortex only, MEPs were seen in both left and right RA muscles suggesting some ipsilateral corticospinal innervation. The latency of the right (ipsilateral) response was approximately 2 ms longer than the left. Comparison with studies in hand and leg muscles suggests that the facilitation pattern in RA may reflect a substantial degree of corticospinal innervation. Experimental Physiology (2001) 86.1, 131-136.     

Periodic increases in force during sustained contraction reduce fatigue and facilitate spatial redistribution of trapezius muscle activity

This study compared fatigue and the spatial distribution of upper trapezius electromyographic (EMG) amplitude during a 6-min constant force shoulder elevation task at 20% of the maximal voluntary contraction force (MVC) (constant force) and during the same task interrupted by brief (2 s) periodic increases in force to 25% MVC every 30 s (variable force). Surface EMG signals were recorded with a 13 × 5 grid of electrodes from the upper trapezius muscle of nine healthy subjects. The centroid (center of activity) of the EMG root mean square map was computed to assess changes over time in the spatial distribution of EMG amplitude. MVC force decreased by (mean ± SD) 9.0 ± 3.9% after the constant force task (P < 0.05) but was unchanged following the variable force contraction. The centroid of EMG amplitude shifted in the cranial direction across the duration of the variable force contraction (P < 0.05) but not during the constant force contraction (shift of 2.9 ± 2.3 mm and 1.4 ± 1.1 mm, respectively). The results demonstrate that periodic increases in force during a sustained contraction enhance the modifications in spatial distribution of upper trapezius EMG amplitude and reduce fatigue compared to a constant force contraction performed at a lower average load. The change in spatial distribution of EMG amplitude over time during a sustained contraction may reflect a mechanism to counteract fatigue during prolonged muscle activity.     

H-reflex and reciprocal Ia inhibition after fatiguing isometric voluntary contraction in soleus muscle

This study investigated the H-reflex and reciprocal Ia inhibition during fatigue in the human soleus muscle. Ten healthy subjects participated in this study, and performed intermittent isometric voluntary contraction of the ankle plantarflexion at 50% MVC as the fatiguing task. Reciprocal Ia inhibition was evaluated by the degree of H-reflex amplitude depression in the soleus muscle by the test stimulus following conditioning stimulus to the common peroneal nerve. The difference in H-reflex amplitude between before and after fatiguing task was also checked. There was no significant difference in the degree of H-reflex amplitude depression, although the H-reflex amplitude significantly decreased after the fatiguing task (p < 0.01). From the results of this study, it was considered that the decrease in H-reflex amplitude was caused by descending inhibitory input from the supraspinal to alpha-motoneuron, and the excitability of the Ia inhibitory interneuron was not involved. It was suggested that the function of reciprocal Ia inhibition was difficult to modulate during fatigue caused by isometric voluntary contraction in this study.     

EMG amplitude distribution changes over the upper trapezius muscle are similar in sustained and ramp contractions

Aim: To investigate whether global motor unit recruitment to compensate for muscle fatigue during sustained contraction and to regulate force increase during ramp contraction are controlled in similar manners in the upper trapezius muscle. Methods: Fourteen subjects performed a 10‐s ramp contraction from 0% to 90% of maximal voluntary contraction (MVC) and a 3‐min sustained contraction at 25% MVC. Both contractions involved isometric shoulder elevation with a multi‐channel surface electromyographical grid placed on the skin above the muscle. To evaluate the global muscle activation pattern, the changes in spatial amplitude distribution of the sustained and the ramp contraction were examined and compared. Results: In both contraction types, the upper part of the trapezius muscle was spatially non‐uniform (inhomogeneous) activated. Throughout the sustained contraction, the amplitude distribution of the upper trapezius muscle became more similar to the amplitude distribution at higher force levels. Conclusion: These findings support the hypothesis that global motor unit recruitment to compensate for muscle fatigue during a sustained contraction, and to regulate force increase during a ramp contraction is controlled in a similar manner. Consequently, they confirm fundamental principles of motor unit activation based on recordings of limited motor unit samples.     

Relaxation from a voluntary contraction is preceded by increased excitability of motor cortical inhibitory circuits

Termination of a muscle contraction is as important a part of movement as muscle activation yet the mechanisms responsible are less well understood. In the present experiments we examined the possible role of intracortical inhibitory circuits in terminating a 20% maximum isometric contraction of the first dorsal interosseous muscle (FDI) in eight healthy subjects. Subjects performed the task simultaneously with both hands and received single or pairs (at an interstimulus interval of 3 ms to evaluate short interval intracortical inhibition, SICI) of transcranial magnetic stimuli (TMS) via a focal coil over the motor hand area of the left hemisphere at different times before and after the onset of relaxation. The amplitude of the motor-evoked potential (MEP) following a single or a pair of TMS pulses was measured in the right FDI and plotted relative to the onset of relaxation as estimated from the surface electromyogram (EMG) of the left FDI. MEPs were larger during contraction than after relaxation whereas SICI was absent during contraction and reappeared after relaxation. We found that in all subjects, the time course of MEP changes during relaxation was closely fitted by a Boltzmann sigmoidal curve which allowed us to estimate the mean MEP amplitudes as well as the ratio of the amplitudes after single or pairs of TMS pulses (i.e.%SICI) at any time in the task. The data showed that the amplitude of MEPs to single pulse TMS had started to decline at about the same time as the onset of EMG silence. Furthermore, the size of the MEPs evoked by paired pulses decreased up to 30 ms beforehand. The latter suggests that an increase in SICI occurs prior to the onset of MEP changes, and hence that increased cortical inhibition may play a role in suppressing corticospinal excitability during relaxation. A subsidiary experiment showed that the time relations of changes in SICI and MEP were unchanged by a period of 10 min training on the task.     

Cortical control of human soleus muscle during volitional and postural activities studied using focal magnetic stimulation

The surface-recorded electromyographic (EMG) responses evoked in the ankle musculature by focal, transcranial, magnetic stimulation of the motor cortex were studied in healthy human subjects. Such soleus evoked motor responses (EMRs) were characterised over a wide range of background levels of motor activity and using different stimulus intensities. EMRs were recorded during predominantly (1) volitional and (2) postural tasks. In the former task subjects were seated and voluntarily produced prescribed levels of soleus activation by reference to a visual monitor of EMG. In the latter task subjects assumed standing postures without EMG feedback. Comparison of the EMRs of soleus, traditionally considered a slow anti-gravity extensor muscle, during these tasks was used to evaluate its cortical control in primarily volitional versus primarily postural activities. The form of soleus EMRs produced by single magnetic cortical stimuli comprised an initial (approx. 30 ms) increase and subsequent (approx. 50 ms) depression of EMG. Cortical stimulation could elicit substantial excitatory soleus EMG responses; for example, responses evoked by mild, magnetic stimuli (125% threshold for inducing a response in the relaxed muscle) as subjects exerted full voluntary plantarflexor effort averaged almost 20% of the maximum M-wave which could be elicited by an electrical stimulus to the posterior tibial nerve. Excitatory EMRs could be elicited in the voluntarily relaxed soleus muscle of the majority of subjects during sitting. The amplitude of soleus responses, induced by threshold stimuli for the relaxed state or approximately 125% threshold intensity, increased approximately linearly with background EMG over a wide range of volitional contraction levels. By contrast, there was no systematic change in the latency of excitatory soleus EMRs with increasing voluntary effort. The excitatory responses evoked in the voluntarily relaxed soleus of seated subjects by magnetic stimulation were regularly facilitated by incremental, voluntary contraction of the contralateral ankle extensors in a graded manner. However, such facilitation of responses was not observed when subjects voluntarily activated the muscle in which EMRs were elicited. The pattern of the responses elicited in soleus by magnetic stimulation during the postural task generally resembled that found during the volitional task. The amplitudes of excitatory soleus EMRs at a given stimulus intensity, obtained when subjects stood quietly, leaned forwards or stood on their toes to produce differing levels of ankle extensor contraction, increased with background EMG. Overall, the relationship between the size of cortically evoked soleus responses and the tonic level of motor activity, observed in individual subjects at matched stimulus intensities, did not consistently differ between postural and volitional tasks. The present results suggest that the motor cortex is potentially capable of exerting rapid regulation of the soleus muscle, and presumably other ankle extensors, not only when the muscle participates in volitional tasks but also when it is engaged in postural maintenance.     

Prior history of FDI muscle contraction: different effect on MEP amplitude and muscle activity

Motor evoked potentials (MEPs) in the right first dorsal interosseous (FDI) muscle elicited by transcranial magnetic stimulation of left motor cortex were assessed in ten healthy subjects during maintenance of a fixed FDI contraction level. Subjects maintained an integrated EMG (IEMG) level with visual feedback and reproduced this level by memory afterwards in the following tasks: stationary FDI muscle contraction at the level of 40 ± 5 % of its maximum voluntary contraction (MVC; 40 % task), at the level of 20 ± 5 % MVC (20 % task), and also when 20 % MVC was preceded by either no contraction (0–20 task), by stronger muscle contraction (40–20 task) or by no contraction with a previous strong contraction (40–0–20 task). The results show that the IEMG level was within the prescribed limits when 20 and 40 % stationary tasks were executed with and without visual feedback. In 0–20, 40–20, and 40–0–20 tasks, 20 % IEMG level was precisely controlled in the presence of visual feedback, but without visual feedback the IEMG and force during 20 % IEMG maintenance were significantly higher in the 40–0–20 task than those in 0–20 and 40–20 tasks. That is, without visual feedback, there were significant variations in muscle activity due to different prehistory of contraction. In stationary tasks, MEP amplitudes in 40 % task were higher than in 20 % task. MEPs did not differ significantly during maintenance of the 20 % level in tasks with different prehistory of muscle contraction with and without visual feedback. Thus, in spite of variations in muscle background activity due to different prehistory of contraction MEPs did not vary significantly. This dissociation suggests that the voluntary maintenance of IEMG level is determined not only by cortical mechanisms, as reflected by corticospinal excitability, but also by lower levels of CNS, where afferent signals and influences from other brain structures and spinal cord are convergent.     

Differential changes in corticospinal and Ia input to tibialis anterior and soleus motor neurones during voluntary contraction in man

Motor-evoked potentials (MEPs) were recorded in the tibialis anterior and soleus muscles following transcranial magnetic stimulation (TMS) of the motor cortex. In the soleus, the H-reflex amplitude increased with the contraction level to the same extent as that of MEPs, whereas in the tibialis anterior, the H-reflex amplitude increased significantly less than that of MEPs. The latency of the MEPs decreased with contraction, whereas this was not the case of the H-reflexes. In the tibialis anterior, the response probability of single-motor units (SMU) to TMS increased more substantially during voluntary contraction than following stimulation of the peroneal nerve. In the tibialis anterior, the response probability of SMU increased more substantially during voluntary contraction than following stimulation of the peroneal nerve. The short-latency facilitation, presumably monosynaptic of origin, of the soleus H-reflex evoked by subthreshold TMS increased as a function of the plantarflexion force. This was not the case for the heteronymous Ia facilitation of the soleus H-reflex following stimulation of the femoral nerve. It is concluded that the corticospinal input to lower limb motor neurones generated by TMS increases with the level of voluntary contraction, whereas this is true only to a limited extent for the synaptic input from Ia afferents. It is suggested that this reflects changes in the susceptibility of corticospinal cells to TMS during voluntary contraction.     

Changes in soleus motoneuron pool reflex excitability and surface EMG parameters during fatiguing low- vs. high-intensity isometric contractions

The fatigue-related changes in soleus motoneuron pool reflex excitability and surface electromyography (EMG) parameters, and maximal voluntary contraction (MVC) force of the plantarflexor (PF) muscles during repeatedly sustained low- (30% MVC) vs. high-intensity (70% MVC) isometric contractions were evaluated Twelve young men with mean (+/- SE) age of 22.4 +/- 0.3 years participated in two fatigue tasks on separate days with at least 1-week interval. The fatigue task consisted of three sustained isometric contractions of PF muscles at a target force level until exhaustion separated with 2-min pause between contractions. M-wave (muscle compound action potential) amplitude (M(max)), Hoffmann reflex maximal amplitude (H(max)) to M-wave amplitude ratio (H(max)/M(max)), and root mean square amplitude (RMS) and median frequency (MF) of EMG power spectrum were recorded from the soleus muscle. The M(max) remained constant immediately post-fatigue and during recovery for low- and high-intensity fatigue tasks, whereas H(max)/M(max) was significantly (p < 0.05) reduced only after high-intensity fatigue task. The increase in RMS and decrease in MF during isometric contractions, and reduction in MVC force immediately after the exercise was greater (p < 0.05) for low-intensity fatigue task. We conclude that low-intensity isometric contractions, repeatedly sustained to fatigue, resulted in a marked increase in the EMG amplitude and spectral compression without a significant post-fatigue reflex inhibition of soleus motoneuron pool. High-intensity contractions, however, resulted in post-fatigue reflex inhibition of soleus motoneuron pool and less pronounced EMG spectral compression during fatiguing contractions. A failure of neuromuscular transmission-propagation was not evident after repetitive fatiguing isometric contractions.     

Altered responses of human elbow flexors to peripheral-nerve and cortical stimulation during a sustained maximal voluntary contraction

 The short-latency electromyographic response evoked by transcranial magnetic stimulation (MEP) increases in size during fatigue, but the mechanisms are unclear. Because large changes occur in the muscle action potential, we tested whether changes in the response to stimulation of the peripheral motor nerve could fully account for the increase in the MEP. Subjects (n=8) performed sustained maximal voluntary contractions (MVCs) of the right elbow flexors for 2 min. During the contraction, the MEP and the response to supramaximal stimulation of motor-nerve fibres in the brachial plexus were alternately recorded. During the contraction, responses to motor-nerve stimulation increased in area by 87±35% (mean±SD) in the biceps brachii and 74±30% in the brachioradialis, but the area of the MEPs increased by 153±86% and 175±122%, respectively. Thus, the increase in the MEP was greater than the increase in the peripheral M-wave. The onset latency of the MEP in the biceps brachii increased by 0.7±0.6 ms (range: –0.2 to 1.9 ms) during the sustained contraction. A smaller increase occurred in response to peripheral nerve stimulation (0.3±0.3 ms; from –0.3 to 0.9 ms). In the contralateral elbow flexors, neither responses to transcranial magnetic stimulation nor responses to motor-nerve stimulation changed in size or latency. During the sustained contraction, the short silent period after stimulation of the peripheral nerve (48±5 ms in biceps brachii and 48±4 ms in brachioradialis) increased in duration by about 12 ms (to 61±12 ms and 60±9 ms, respectively), whereas the silent period following transcranial magnetic stimulation increased from 238±39 ms in biceps brachii and 243±34 ms in brachioradialis to 325±41 ms and 343±42 ms, respectively. During a sustained MVC, while the motor responses to peripheral and to cortical stimulation grow concurrently, growth of the MEP cannot be entirely accounted for by changes in the muscle action potential. Hence, some of the increase in MEP size during fatigue must reflect changes in the central nervous system. Increased latency of the MEPs and lengthening of the peripherally evoked silent period are consistent with decreased excitability of the alpha motoneurone pool. Thus, an increased response from the motor cortex to the magnetic stimulus remains a likely contributor to the increase in the size of the MEP in fatigue. Received: 11 September 1998 / Accepted: 28 January 1999     

Failure of activation of spinal motoneurones after muscle fatigue in healthy subjects studied by transcranial magnetic stimulation

During a sustained maximal effort a progressive decline in the ability to drive motoneurones (MNs) develops. We used the recently developed triple stimulation technique (TST) to study corticospinal conduction after fatiguing exercise in healthy subjects. This method employs a collision technique to estimate the proportion of motor units activated by a transcranial magnetic stimulus. Following a sustained contraction of the abductor digiti minimi muscle at 50 % maximal force maintained to exhaustion there was an immediate reduction of the TST response from >95% to about 60%. This effect recovered to control levels within 1 min and implies that a decreased number of spinal MNs were excited. Additional TST experiments after maximal and submaximal efforts showed that the decrease in size of the TST response was related to duration and strength of exercise. Motor evoked potentials (MEPs) after conventional transcranial magnetic stimulation (TMS) and responses to peripheral nerve stimulation were recorded following the same fatigue protocol. The size of both the MEPs and the peripheral responses increased after the contraction and were in direct contrast to the decrease in size of the TST response. This points to increased probability of repetitive spinal MN activation during fatigue even if some MNs in the pool failed to discharge. Silent period duration following cortical stimulation lengthened by an average of 55 ms after the contraction and recovered within a time course similar to that of the TST response depression. Overall, the results suggest that the outflow from the motor cortex could become insufficient to drive all spinal MNs to discharge when the muscle is fatigued and that complex interactions between failure of activation and compensatory mechanisms to maintain motor unit activation occur during sustained voluntary activity. When inability to maintain force occurs during submaximal effort, failure of activation of motor units is predominant.     

Muscle weakness following sustained and rhythmic isometric contractions in man

Summary The effects of sustained and rhythmically performed isometric contractions on electrically evoked twitch and tetanic force generation of the triceps surae have been investigated in 4 healthy male subjects. The isometric contractions were performed separately and on different occasions at 30%, 60% and 100% of the force of maximal voluntary contraction (MVC). The area under the maximal voluntary contraction (MVC) force/ time curve during the rhythmic and sustained contractions was the same for each experiment. The results showed that following rhythmic isometric exercise there was a small decrease in low (10 and 20 Hz) and high (40 Hz) frequency tetanic tension which was associated with % MVC. However, there was no change in the 20/40 ratio of tetanic forces, MVC or the contraction times and force of the maximal twitch. In contrast, following sustained isometric exercise tetanic forces were markedly reduced, particularly at low frequencies of stimulation. The 20/40 ratio decreased and the induced muscle weakness was greater at 30% than 60% or 100% MVC. The performance of sustained isometric contractions also effected a decrease in contraction time of the twitch and MVC. The results are in accord with previous findings for dynamic work (Davies and White 1982), and show that if isometric exercise is performed rhythmically the effect on tetanic tensions is small and there is no evidence of a preferential loss of electrically evoked force at either high or low frequencies of stimulation following the contractions. For sustained contractions, however, the opposite is true, the ratio of 20/40 Hz forces is markedly reduced and following 30% sustained MVC there is a significant (p<0.05) change in the time to peak tension (TPT) of the maximal twitch.     

Intracortical modulation of cortical-bulbar responses for the masseter muscle

Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated in the masseter muscles of 12 subjects and the cortical silent period (SP) in nine subjects. Motor evoked potentials (MEPs) were recorded from contralateral (cMM) and ipsilateral (iMM) masseters, activated at 10% of maximal voluntary contraction (MVC). Interstimulus intervals (ISIs) were 2 and 3 ms for SICI, 10 and 15 ms for ICF. TMS of the left masseteric cortex induced MEPs that were larger in the cMM than the iMM; stimulation of right masseteric cortex produced a similar asymmetry in response amplitude. SICI was only observed using a CS intensity of 70% AMT and was equal in both cMM and iMM. SICI was stronger at higher TS intensities, was abolished by muscle activation greater than 10% MVC, and was unaffected by coil orientation changes. Control experiments confirmed that SICI was not contaminated by any inhibitory peripheral reflexes. However, ICF could not be obtained because it was masked by bilateral reflex depression of masseter EMG caused by auditory input from the coil discharge. The SP was bilateral and symmetric; its duration ranged from 35 to 70 ms depending on TS intensity and coil orientation. We conclude that SICI is present in the cortical representation of masseter muscles. The similarity of SICI in cMM and iMM suggests either that a single pool of inhibitory interneurons controls ipsi- and contralateral corticotrigeminal projections or that inhibition is directed to bilaterally projecting corticotrigeminal fibres. Finally, the corticotrigeminal projection seems to be weakly influenced by inhibitory interneurons mediating the cortical SP.     

Evaluations of inhibitory effect on the motor cortex by cutaneous pain via application of capsaicin

To evaluation the effect of experimental tonic cutaneous pain on motor cortex excitability by means of transcranial magnetic stimulation (TMS). Thirty healthy adults (male: 12, female: 18) were tested with TMS. Cutaneous pain was induced by topical application of capsaicin cream (0.025%) on the skin overlying the flexor carpi radialis of dominant limb. And the cream had been under an occlusive dressing for 40 minutes until we removed it. Magnetic stimulation was performed to the contralateral cortex with a circular coil at 80% intensity of maximum stimulator output. MEPs were recorded at flexor carpi radialis (FCR), extensor carpi radialis (ECR) and opponens pollicis (OP) with constant isometric contraction of 10%, 30% maximal voluntary contraction (MVC). Main outcome measures the intensity of pain by visual analog scale (VAS). The latency, amplitude and silent period of motor evoked potentials (MEPs). Values at baseline and 20, 40, 60, 80 minutes from applying capsaicin were compared. VAS score reached the peak value at 40 minutes. Amplitudes of MEPs at FCR progressively decreased up to 40 minutes than returned to nearly baseline value at 80 minutes. The decrease in MEP amplitude at FCR was accompanied by the increase in VAS score significantly and sustained for 20 min after washing out capsaicin cream. At ECR & OP, we could not demonstrate any changes in amplitude with time. Silent period at FCR only was significantly prolonged with the increase in VAS score. The present findings support that noxious cutaneous stimulation inhibit motor cortex excitability by so-called cortico-cortical circuits.     

Origin of facilitation of motor-evoked potentials after paired magnetic stimulation: direct recording of epidural activity in conscious humans

A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below active threshold for obtaining motor-evoked potentials (MEPs) facilitates EMG responses evoked at rest in hand muscles by a suprathreshold magnetic stimulus given 10-25 ms later. This is known as intracortical facilitation (ICF). We recorded descending volleys produced by single and paired magnetic motor cortex stimulation through high cervical epidural electrodes implanted for pain relief in six conscious patients. At interstimulus intervals (ISIs) of 10 and 15 ms, although MEP was facilitated, there was no change in the amplitude or number of descending volleys. An additional I wave sometimes was observed at 25 ms ISI. In one subject, we also evaluated the effects of reversing the direction of the induced current in the brain. At 10 ms ISI, the facilitation of the MEPs disappeared and was replaced by slight suppression; at 2 ms ISI, there was a pronounced facilitation of epidural volleys. Subsequent experiments on healthy subjects showed that a conditioning stimulus capable of producing ICF of MEPs had no effect on the EMG response evoked by transmastoidal electrical stimulation of corticospinal tract. We conclude that ICF occurs because either 1) the conditioning stimulus has a (thus far undetected) effect on spinal cord excitability that increases its response to the same amplitude test volley or 2) that it can alter the composition (but not the amplitude) of the descending volleys set up by the test stimulus such that a larger proportion of the activity is destined for the target muscle.     

Stability of corticospinal excitability and grip force in intrinsic hand muscles in man over a 24-h period

The maximum voluntary muscle force can vary throughout the day; typically being low in the morning and high in the evening. The nature of this possible variation has been investigated with respect to corticospinal excitability. Six healthy subjects were studied. Maximum voluntary contraction (MVC) in the thenar muscles was measured. In addition, we monitored several indices of corticospinal excitability using electromyographic (EMG) recording and transcranial magnetic stimulation (TMS) of the motor cortex. Motor evoked potentials (MEPs) were recorded while relaxed and at 10% MVC when the silent period was assessed as an index of corticospinal inhibition. Readings were taken every 3 h for 24 h. MVC of the thenar muscles did not change significantly over the 24 h. The mean areas, latencies and durations of MEPs did not show significant changes over the 24-h test period with the muscle relaxed or contracted; however, MEP area did vary between sessions at all stimulus intensities suggesting non-time-of-day-dependent changes in corticospinal excitability. Furthermore, the extent and duration of the silent period seen after the MEP in the contracted muscle did not change significantly over the 24 h of the experiment at any stimulus intensity. These results provide evidence that the MVC force of the thenar muscles and their responses to TMS are stable throughout the course of the day and suggest that, in hand muscles, corticospinal excitability may not be subject to circadian variation.     

Two phases of short-interval intracortical inhibition

Short-interval intracortical inhibition (SICI) is a widely used method to study cortical inhibition, and abnormalities have been found in several neurological and psychiatric disorders. Previous studies suggested that SICI involves two phases and the first phase may be explained by axonal refractoriness. Our objectives are to further investigate the mechanisms of the two phases of SICI. SICI was studied in 11 normal volunteers by a paired transcranial magnetic stimulation (TMS) paradigm applied to the left motor cortex with a subthreshold conditioning stimulus (80% resting motor threshold for rest condition and 95% active motor threshold for active condition) followed by a suprathreshold test stimulus at interstimulus intervals (ISIs) of 1–4.5 ms in steps of 0.5 ms. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle. Three different test stimulus intensities adjusted to produce 0.2, 1 and 4 mV MEPs at rest were studied with the target muscle relaxed and during 20% maximum contraction. Maximum inhibition was observed at ISIs of 1 ms and 2.5 ms for the rest condition and the difference among ISIs was reduced with voluntary contraction. SICI increased with larger test MEP amplitude and decreased with voluntary contraction. At test MEP of 0.2 mV, some subjects showed facilitation and this is likely related to short-interval intracortical facilitation. For rest SICI, the correlation between adjacent ISIs was much higher from 3 to 4.5 ms than from 1 to 2.5 ms or between 1 and 2.5 ms. There was no correlation between SICI at different test MEP amplitudes. We conclude that maximum SICI at ISIs of 1 and 2.5 ms are mediated by different mechanisms. SICI at 1 ms cannot be fully explained by axonal refractoriness and synaptic inhibition may be involved. SICI is a complex phenomenon and inhibition at different ISIs may be mediated by different inhibitory circuits.     

Modulation of corticospinal excitability dependent upon imagined force level

Motor imagery is defined as the mental execution of a movement without any muscle activity. In the present study, corticospinal excitability was assessed by motor evoked potentials (MEPs) when the subjects imagined isometric elbow flexion at various force levels. Electromyography was recorded from the right brachioradialis, the biceps brachii and the triceps brachii muscles. First, the maximum voluntary contraction (MVC) of elbow flexion was recorded in each subject. Subjects practiced performing 10, 30 and 60 % MVC using visual feedback. After the practice, MEPs were recorded during the imagery of elbow flexion with the forces of 10, 30 and 60 % MVC without any feedback. After the MEPs recording, we assigned subjects to reproduce the actual elbow flexion force at 10, 30 and 60 % MVC. The MEPs amplitudes in the brachioradialis and biceps brachii in the 60 % MVC condition were significantly greater than those in the 10 % MVC condition (p < 0.05). These findings suggest that the enhancement of corticospinal excitability during motor imagery is associated with an increase in imagined force level.