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Recombinant human erythropoietin (EPO) increases exercise capacity by stimulating erythropoiesis and subsequently enhancing oxygen delivery to the working muscles. In a large dose, EPO crosses the BBB and may reduce central fatigue and improve cognition. In turn, this would augment exercise capacity independent of erythropoiesis. To test this hypothesis, 15 healthy young men (18-34 years old, 74 + or - 7 kg) received either 3 days of high-dose (30,000 IU/day; n = 7) double-blinded placebo controlled or 3 mo of low-dose (5,000 IU/wk; n = 8) counter-balanced open but controlled administration of EPO. We recorded exercise capacity, transcranial ultrasonography-derived middle cerebral artery blood velocity, and arterial-internal jugular venous concentration differences of glucose and lactate. In addition, cognitive function, ratings of perceived exertion, ventilation, and voluntary activation by transcranial magnetic stimulation-induced twitch force were evaluated. Although EPO in a high dose increased cerebrospinal fluid EPO concentration approximately 20-fold and affected ventilation and cerebral glucose and lactate metabolism (P < 0.05), 3 days of high-dose EPO administration had no effect on cognition, voluntary activation, or exercise capacity, but ratings of perceived exertion increased (P < 0.05). We confirmed that 3 mo of administration of EPO increases exercise capacity, but the improvement could not be accounted for by other mechanisms than enhanced oxygen delivery. In conclusion, EPO does not attenuate central fatigue or change cognitive performance strategy, suggesting that EPO enhances exercise capacity exclusively by increased oxygen delivery to the working muscles.

Aim: Changes in sensory information from active muscles accompany fatiguing exercise and the force-generating capacity deteriorates. The central motor commands therefore must adjust depending on the task performed. Muscle potentials evoked by transcranial magnetic stimulation (TMS) change during the course of fatiguing muscle activity, which demonstrates activity changes in cortical or spinal networks during fatiguing exercise. Here, we investigate cortical mechanisms that are actively involved in driving the contracting muscles., Methods: During a sustained submaximal contraction (30% of maximal voluntary contraction) of the elbow flexor muscles we applied TMS over the motor cortex. At an intensity below motor threshold, TMS reduced the ongoing muscle activity in biceps brachii. This reduction appears as a suppression at short latency of the stimulus-triggered average of rectified electromyographic (EMG) activity. The magnitude of the suppression was evaluated relative to the mean EMG activity during the 50 ms prior to the cortical stimulus., Results: During the first 2 min of the fatiguing muscle contraction the suppression was 10 +/- 0.9% of the ongoing EMG activity. At 2 min prior to task failure the suppression had reached 16 +/- 2.1%. In control experiments without fatigue we did not find a similar increase in suppression with increasing levels of ongoing EMG activity., Conclusion: Using a form of TMS which reduces cortical output to motor neurones (and disfacilitates them), this study suggests that neuromuscular fatigue increases this disfacilitatory effect. This finding is consistent with an increase in the excitability of inhibitory circuits controlling corticospinal output.

Maximal exercise may be limited by central fatigue defined as an inability of the central nervous system to fully recruit the involved muscles. This study evaluated whether a reduction in the cerebral oxygen-to-carbohydrate index (OCI) and in the cerebral mitochondrial oxygen tension relate to the ability to generate a maximal voluntary contraction and to the transcranial magnetic stimulated force generation. To determine the role of a reduced OCI and in central fatigue, 16 males performed low intensity, maximal intensity and hypoxic cycling exercise. Exercise fatigue was evaluated by ratings of perceived exertion (RPE), arm maximal voluntary force (MVC), and voluntary activation of elbow flexor muscles assessed with transcranial magnetic stimulation. Low intensity exercise did not produce any indication of central fatigue or marked cerebral metabolic deviations. Exercise in hypoxia (0.10) reduced cerebral oxygen delivery 25% and decreased 11+/-4 mmHg (P<0.001) together with OCI (6.2+/-0.7 to 4.8+/-0.5, P<0.001). RPE increased while MVC and voluntary activation were reduced (P<0.05). During maximal exercise declined 8+/-4 mmHg (P<0.05) and OCI to 3.8+/-0.5 (P<0.001). RPE was 18.5, and MVC and voluntary activation were reduced (P<0.05). We observed no signs of muscular fatigue in the elbow flexors and all control MVCs were similar to resting values. Exhaustive exercise provoked cerebral deoxygenation, metabolic changes and indices of fatigue similar to those observed during exercise in hypoxia indicating that reduced cerebral oxygenation may play a role in the development of central fatigue and may be an exercise capacity limiting factor.

This review considers the operation of the corticospinal system in primates. There is a relatively widespread cortical area containing corticospinal outputs to a single muscle and thus a motoneurone pool receives corticospinal input from a wide region of the cortex. In addition, corticospinal cells themselves have divergent intraspinal branches which innervate more than one motoneuronal pool but the synergistic couplings involving the many hand muscles are likely to be more diverse than can be accommodated simply by fixed patterns of corticospinal divergence. Many studies using transcranial magnetic stimulation of the human motor cortex have highlighted the capacity of the cortex to modify its apparent excitability in response to altered afferent inputs, training and various pathologies. Studies using cortical stimulation at 'very low' intensities which elicit only short-latency suppression of the discharge of motor units have revealed that the rapidly conducting corticospinal axons (stimulated at higher intensities) drive motoneurones in normal voluntary contractions. There are also major non-linearities generated at a spinal level in the relation between corticospinal output and the output from the motoneurone pool. For example, recent studies have revealed that the efficacy of the human corticospinal connection with motoneurones undergoes activity-dependent changes which influence the size of voluntary contractions. Hence, corticospinal drives must be sculpted continuously to compensate for the changing functional efficacy of the descending systems which activate the motoneurones. This highlights the need for proprioceptive monitoring of movements to ensure their accurate execution.

Time- and frequency-domain analysis of the coupling between pairs of electromyograms (EMG) recorded from leg muscles was investigated during walking in healthy human subjects. For two independent surface EMG signals from the tibialis anterior (TA) muscle, coupling estimated from coherence measurements was observed at frequencies

In 35 healthy human subjects coupling of EMGs recorded from the tibialis anterior (TA) and soleus (Sol) muscles during voluntary co-contraction was analysed in the time and frequency domains. Two patterns were observed in different subjects or in the same subject on different occasions. One pattern consisted of central peaks in the cumulant density function of the two signals, which was often accompanied by coherence in the 15-35 Hz frequency band. The other pattern consisted of a central trough in the cumulant density function, which was mostly accompanied by coherence around 10 Hz. When this was the case oscillations were usually observed in the cumulant density function with time lags of 100 ms. Both patterns could be observed in the same subject, but usually not at the same time. Coherence around 10 Hz associated with a central trough in the cumulant density function was less common during weak than during strong co-contraction. The central peak with coherence in the 15-35 Hz frequency band in contrast tended to be most common during weak contraction. There was a tendency for the 10-Hz coherence with central trough to occur when the contractions had been maintained for some time. Both patterns could be observed when sensory feedback in large diameter afferents was blocked by ischaemia. When a central peak with coherence in the 15-35 Hz frequency band was observed for paired TA and Sol EMG recordings (10 out of 19 subjects), a coupling in the same frequency band was also observed between the EMG activities from the two muscles and the EEG activity recorded from the leg area of the motor cortex. When the central trough and the coherence around 10 Hz was observed for the EMG recordings (8 out of 19 subjects), no significant coherence was observed between EEG and EMG in 7 of the 8 subjects. In the last subject coherence around 10 Hz was observed. It is suggested that these findings signify the existence of two different central input systems to antagonistic ankle motoneurones: one input activates one muscle while depressing the antagonist and the other coactivates antagonistic motoneurones. The data suggest that at least the latter input depends on motor cortical activity.

Transcranial magnetic stimulation activates corticospinal neurones directly and transsynaptically and hence, activates motoneurones and results in a response in the muscle. Transmastoid stimulation results in a similar muscle response through activation of axons in the spinal cord. This study was designed to determine whether the two stimuli activate the same descending axons. Responses to transcranial magnetic stimuli paired with electrical transmastoid stimuli were examined in biceps brachii in human subjects. Twelve interstimulus intervals (ISIs) from -6 ms (magnet before transmastoid) to 5 ms were investigated. When responses to the individual stimuli were set at 10-15 % of the maximal M-wave, responses to the paired stimuli were larger than expected at ISIs of -6 and -5 ms but were reduced in size at ISIs of -2 to 1 ms and at 3 to 5 ms. With individual responses of 3-5 % of maximal M-wave, facilitation still occurred at ISIs of -6 and -5 ms and depression of the paired response at ISIs of 0, 1, 4 and 5 ms. The interaction of the response to transmastoid stimulation with the multiple descending volleys elicited by magnetic stimulation of the cortex is complex. However, depression of the response to the paired stimuli at short ISIs is consistent with an occlusive interaction in which an antidromic volley evoked by the transmastoid stimulus collides with and annihilates descending action potentials evoked by the transcranial magnetic stimulus. Thus, it is consistent with the two stimuli activating some of the same corticospinal axons.

1. In human subjects, a high-voltage electrical pulse between electrodes fixed over the mastoid processes activates descending tract axons at the level of the cervico-medullary junction to produce motor responses (cevicomedullary evoked responses; CMEPs) in the biceps brachii and brachioradialis muscles. 2. During isometric maximal voluntary contractions (MVCs) of the elbow flexors, CMEPs in the biceps brachii and brachioradialis muscles are sometimes followed by a second compound muscle action potential. This response can be observed in single trials (amplitude of up to 60 % of the maximal M wave) and follows the CMEP by about 16 ms in both muscles. The response only occurs during very strong voluntary contractions. 3. The second response following transmastoid stimulation appears with stimulation intensities that are at the threshold for evoking a CMEP in the contracting muscles. The response grows with increasing stimulus intensity, but then decreases in amplitude and finally disappears at high stimulation intensities. 4. A single stimulus to the brachial plexus during MVCs can also elicit a second response (following the M wave) in the biceps brachii and brachioradialis muscles. The latency of this response is 3-4 ms longer than that of the second response observed following transmastoid stimulation. This difference in latency is consistent with a reflex response to stimulation of large-diameter afferents. 5. The amplitude of the second response to transmastoid stimulation can be reduced by appropriately timed subthreshold transcranial magnetic stimuli. This result is consistent with intracortical inhibition of the response. 6. We suggest that transmastoid stimulation can elicit a large transcortical reflex response in the biceps brachii and brachioradialis muscles. The response travels via the motor cortex but is only apparent during near-maximal voluntary efforts.

Synchronization of motor unit activity was investigated during treadmill walking (speed: 3-4 km/h) in 25 healthy human subjects. Recordings were made by pairs of wire electrodes inserted into the tibialis anterior (TA) muscle and by pairs of surface electrodes placed over this muscle and a number of other lower limb muscles (soleus, gastrocnemius lateralis, gastrocnemius medialis, biceps femoris, vastus lateralis, and vastus medialis). Short-lasting synchronization (average duration: 9.6 +/- 1.1 ms) was observed between spike trains generated from multiunit electromyographic (EMG) signals recorded by the wire electrodes in TA in eight of nine subjects. Synchronization with a slightly longer duration (12.8 +/- 1.2 ms) was also found in 13 of 14 subjects for paired TA surface EMG recordings. The duration and size of this synchronization was within the same range as that observed during tonic dorsiflexion in sitting subjects. There was no relationship between the amount of synchronization and the speed of walking. Synchronization was also observed for pairs of surface EMG recordings from different ankle plantarflexors (soleus, medial gastrocnemius, and lateral gastrocnemius) and knee extensors (vastus lateralis and medialis of quadriceps), but not or rarely for paired recordings from ankle and knee muscles. The data demonstrate that human motor units within a muscle as well as synergistic muscles acting on the same joint receive a common synaptic drive during human gait. It is speculated that the common drive responsible for the motor unit synchronization during gait may be similar to that responsible for short-term synchronization during tonic voluntary contraction.

The aim of the present study was to investigate the contribution of reciprocal inhibition to muscle tone by examining the transmission in the reciprocal inhibitory pathway in patients with a known defect in the glycine receptor. The study was performed in eight patients with hereditary hyperekplexia, six with the major form and two with the minor form of the disease. A mutation in the alpha1-subunit of the glycine receptor had been demonstrated in the patients with the major form, whereas no mutation was seen in the patients with the minor form. Disynaptic reciprocal inhibition, which is presumed to be mediated by glycine, was not seen in the patients with the major form of the disease, while it could be evoked in the patients with the minor form of the disease. Presynaptic inhibition, which is presumed to be mediated by GABA, was seen in both types of patients. It is concluded that the major form of hereditary hyperekplexia is associated with impaired transmission in glycinergic reciprocal inhibitory pathways. The findings demonstrate the importance of reciprocal inhibition for the muscle tone in man, and it is suggested that the impaired reciprocal inhibition seen in patients with a defect in the glycine receptor may contribute to the increased muscle stiffness that is observed in these patients.

The existence of transcortical reflex pathways in the control of distal arm and hand muscles in man is now widely accepted. Much more controversy exists regarding a possible contribution of such reflexes to the control of leg muscles. It is often assumed that transcortical reflex pathways play no, or only a minor, role in the control of leg muscles. Transcortical reflex pathways according to this view are reserved for the control of the distal upper limb and are seen in close relation to the evolution of the primate hand. Here we review data, which provide evidence that transcortical reflexes do exist for lower limb muscles and may play a significant role in the control of at least some of these muscles. This evidence is based on animal research, recent experiments combining transcranial magnetic stimulation with peripheral electrical and mechanical stimulation in healthy subjects and neurological patients. We propose that afferent activity from muscle and skin may play a role in the regulation of bipedal gait through transcortical pathways.

The distribution of monosynaptic and nonmonosynaptic excitation was investigated within flexor carpi radialis (FCR) and extensor carpi radialis (ECR) motoneurone (MN) pools. FCR H reflexes of different size were conditioned by various conditioning stimuli eliciting different effects: (1) musculocutaneous-induced non-monosynaptic excitation of FCR MNs at the onset of biceps contraction, (2) heteronymous monosynaptic Ia facilitation, (3) reciprocal Ia inhibition, and (4) presynaptic inhibition of Ia terminals. Musculocutaneous-induced non-monosynaptic excitation increased continuously with the size of the unconditioned reflex. In contrast, heteronymous monosynaptic Ia excitation first increased and then decreased, with increases in the unconditioned reflex size, reciprocal inhibition and presynaptic inhibition showing an approximately similar tendency. This suggests that the non-monosynaptic excitation is distributed more evenly to early and late recruited MNs than monosynaptic Ia excitation, reciprocal inhibition and presynaptic inhibition. A different pattern of homonymous radial-induced monosynaptic and non-monosynaptic excitation was also found for individual ECR MNs investigated with the poststimulus time histogram (PSTH) method. Whereas the monosynaptic Ia excitation tended to be most marked in lower threshold MUs, the nonmonosynaptic excitation was evenly distributed to lower and higher threshold MUs. We propose that the even distribution of the non-monosynaptic excitation in the motoneuronal pool may be of significance when it is necessary to activate a wide range of MNs more or less simultaneously.

Motor unit firing rates and voluntary activation of muscle decline during sustained isometric contractions. After exercise, the responses to motor cortical and corticospinal stimulation are reduced. These changes may reflect motoneuronal inhibition mediated by group III and IV muscle afferents. To determine whether the post-contraction depression of the responses to corticospinal or motor cortical stimulation could be maintained by continued firing of ischaemically sensitive group III and IV muscle afferents, we examined responses in muscles that were held ischaemic after exercise. Following a sustained maximal voluntary contraction (MVC) of the elbow flexors lasting 2 min, the response to stimulation of the corticospinal tract was reduced but the usual recovery (over approximately 2 min) was not delayed when the muscles were maintained ischaemic for 2 min after the contraction. Following a sustained MVC, the time course of the reduction in the response to motor cortical stimulation (a gradual decrease over approximately 2 min, maintained for > 10 min) was also not altered if the muscle was held ischaemic. Mean arterial blood pressure rose to 155 +/- 12 mmHg during the 2 min MVC, declined to 125 +/- 9 mmHg immediately after it, but remained at this level without returning to pre-exercise levels (102 +/- 10 mmHg) until circulation to the arm was restored. This confirms that the sustained MVC activated a reflex dependent on group III and IV muscle afferents. This study shows that ischaemically sensitive group III and IV muscle afferents do not mediate depression of responses to motor cortical or corticospinal stimulation after fatiguing exercise. It also suggests that firing of such afferents does not directly inhibit motoneurones or motor cortical output cells.

1. The modulation of disynaptic reciprocal inhibition between antagonistic ankle muscles during walking was investigated in 17 healthy human subjects. Inhibition from ankle dorsiflexors to ankle plantar flexors was evoked by stimulation of the common peroneal nerve (CPN) and evaluated as the stimulus-induced depression of rectified soleus EMG activity (latency approx. 40 ms) or the short-latency depression of the soleus H-reflex (conditioning-test intervals around 2-3 ms). In some experiments the inhibition from ankle plantar flexors to ankle dorsiflexors was investigated. In these experiments the tibial nerve was stimulated and the amount of inhibition was evaluated from the short-latency depression of the voluntary rectified tibialis anterior (TA) EMG. 2. The short-latency inhibition of the soleus H-reflex following the CPN stimulation (1.1 x motor threshold; MT) was strongly modulated during walking, being large in the swing phase and absent in the stance phase. 3. A smaller amount of EMG depression following the CPN stimulation (1. 1-1.2 x MT) was observed in the stance phase of walking as compared to tonic or dynamic plantar flexion at a similar background EMG activity level in standing or sitting subjects. 4. In four subjects a depression of the TA EMG activity was produced by stimulation of the tibial nerve (1.1-1.2 x MT). In all subjects a smaller amount of inhibition was observed in the swing phase of walking as compared to tonic dorsiflexion at a comparable EMG activity level. 5. It is concluded that the transmission in the disynaptic Ia reciprocal pathway between ankle plantar flexors and dorsiflexors is modulated during walking. Inhibition from dorsiflexors to plantar flexors seems to be large in swing and small in stance, whereas inhibition from plantar flexors to dorsiflexors seems to be small in swing.

The responses of 34 extensor-carpi-radialis motor units to graded transcranial magnetic stimulation (TMS) and electrical stimulation of the radial nerve were investigated in six human subjects. Simultaneously with the recording of the single motor-unit discharges, motor-evoked potentials (MEPs) and H-reflexes evoked by the two types of stimulation were recorded by surface electrodes and expressed as a percentage of the maximal motor response (Mmax). Ten motor units were activated in the H-reflex when it was less than 5% of Mmax, but not in the MEP even when it was 15% of Mmax. The opposite was observed for three motor units. Eleven motor units were recruited by both stimuli, but with significantly different recruitment thresholds. Only ten motor units had a threshold similar to TMS and radial nerve stimulation. From these observations, we suggest that caution should be taken when making conclusions regarding motor cortical excitability based on changes in the size of MEPs, even when it is ensured that there are no similar changes in background EMG-activity or H-reflexes.

Stimulation of cutaneous foot afferents has been shown to evoke a facilitation of the tibialis anterior (TA) EMG-activity at a latency of 70-95 ms in the early and middle swing phase of human walking. The present study investigated the underlying mechanism for this facilitation. In those subjects in whom it was possible to elicit a reflex during tonic dorsiflexion while seated (6 out of 17 tested), the facilitation in the TA EMG evoked by stimulation of the sural nerve (3 shocks, 3-ms interval, 2.0-2.5x perception threshold) was found to have the same latency in the swing phase of walking. The facilitation observed during tonic dorsiflexion has been suggested to be -- at least partly -- mediated by a transcortical pathway. To investigate whether a similar mechanism contributes to the facilitation observed during walking, magnetic stimulation of the motor cortex (1.2x motor threshold) was applied in the early swing phase at different intervals in relation to the cutaneous stimulation in 17 subjects. In 13 of the subjects, the motor potentials evoked by the magnetic stimulation (MEPs) were more facilitated by prior sural-nerve stimulation (conditioning-test intervals of 50-80 ms) than the algebraic sum of the control MEP and the cutaneous facilitation in the EMG when evoked separately. In four of these subjects, a tibialis anterior H-reflex could also be evoked during walking. In none of the subjects was an increase of the H-reflex similar to that for the MEP observed. In five experiments on four subjects, MEPs evoked by magnetic and electrical cortical stimulation were compared. In four of these experiments, only the magnetically induced MEPs were facilitated by prior stimulation of the sural nerve. We suggest that a transcortical pathway may also contribute to late cutaneous reflexes during walking.

1. The effect of transcranial magnetic stimulation (TMS) on the soleus H reflex was investigated in the stance phase of walking in seventeen human subjects. For comparison, measurements were also made during quiet standing, matched tonic plantar flexion and matched dynamic plantar flexion. 2. During walking and dynamic plantar flexion subliminal (0.95 times threshold for a motor response in the soleus muscle) TMS evoked a large short-latency facilitation (onset at conditioning-test interval: -5 to -1 ms) of the H reflex followed by a later (onset at conditioning-test interval: 3-16 ms) long-lasting inhibition. In contrast, during standing and tonic plantar flexion the short-latency facilitation was either absent or small and the late inhibition was replaced by a long-lasting facilitation. 3. When grading the intensity of TMS it was found that the short-latency facilitation had a lower threshold during walking than during standing and tonic plantar flexion. Regardless of the stimulus intensity the late facilitation was never seen during walking and dynamic plantar flexion and the late inhibition was not seen, except for one subject, during standing and tonic plantar flexion. 4. A similar difference in the threshold of the short-latency facilitation between walking and standing was not observed when the magnetic stimulation was replaced by transcranial electrical stimulation. 5. The lower threshold of the short-latency facilitation evoked by magnetic but not electrical transcranial stimulation during walking compared with standing suggests that cortical cells with direct motoneuronal connections increase their excitability in relation to human walking. The significance of the differences in the late facilitatory and inhibitory effects during the different tasks is unclear.

Changes in reciprocal inhibition from ankle dorsiflexors to ankle plantar flexors were evaluated at increasing levels of tonic plantar flexion in 11 healthy subjects. Stimulation of the common peroneal nerve (CPN) evoked a short-latency depression of the rectified and averaged soleus electromyogram (average latency of depression: 40 ms) and a short-latency inhibition of the soleus H-reflex (conditioning-test interval: 2-3 ms). When the intensity of the CPN stimulation was below approximately 1.2 x motor threshold (x MT) the inhibition of both the soleus EMG (expressed as the amount of EMG during the inhibition as percentage of the background EMG) and the soleus H-reflex (expressed as the size of the conditioned reflex as percentage of the control H-reflex size) were seen to decrease with increasing levels of plantar flexion. At intensities of stimulation higher than approximately 1.2 x MT the inhibition of the EMG and the H-reflex was very strong and was not modulated with contraction. It is suggested that the decrease of reciprocal inhibition with increasing levels of plantar flexion is due to a decreased excitability of the Ia inhibitory interneurones which are responsible for the inhibition. It is emphasized that submaximal stimulation is necessary to demonstrate this modulation of inhibition and that the functional contribution of reciprocal inhibition to motor performance cannot be revealed from the amount of inhibition evoked by artificial electrical stimulation of a peripheral nerve.

1. In human subjects, stretch applied to ankle dorsiflexors elicited three bursts of reflex activity in the tibialis anterior (TA) muscle (labelled M1, M2 and M3) at mean onset latencies of 44, 69 and 95 ms, respectively. The possibility that the later of these reflex bursts is mediated by a transcortical pathway was investigated. 2. The stretch evoked a cerebral potential recorded from the somatosensory cortex at a mean onset latency of 47 ms in nine subjects. In the same subjects a compound motor-evoked potential (MEP) in the TA muscle, evoked by magnetic stimulation of the motor cortex, had a mean onset latency of 32 ms. The M1 and the M2 reflexes thus had too short a latency to be caused by a transcortical pathway (minimum latency, 79 ms (47 + 32)), whereas the later part of the M2 and all of the M3 reflex had a sufficiently long latency. 3. When the transcranial magnetic stimulation was timed so that the MEP arrived in the TA muscle at the same time as the M1 or M2 reflexes, no extra increase in the potential was observed. However, when the MEP arrived at the same time as the M3 reflex a significant (P < 0.01) extra-facilitation was observed in all twelve subjects investigated. 4. Peaks evoked by transcranial magnetic stimulation in the post-stimulus time histogram of the discharge probability of single TA motor units (n = 28) were strongly facilitated when they occurred at the same time as the M3 response. This was not the case for the first peaks evoked by electrical transcranial stimulation in any of nine units investigated. 5. We suggest that these findings are explained by an increased cortical excitability following TA stretch and that this supports the hypothesis that the M3 response in the TA muscle is - at least partly - mediated by a transcortical reflex.

1. Stimulation of the superficial peroneal or the sural nerve (3 shocks, 3 ms interval, 1 ms duration, 2.5 x perception threshold) evoked a reflex activation of the tibialis anterior muscle at a latency of approximately 70-95 ms in all of nine healthy human subjects. Stimulation of the medial plantar nerve only rarely produced similar effects. The possibility that a transcortical pathway contributes to these late reflex responses was investigated by combining the cutaneous stimulations and a transcranial magnetic stimulation of the contralateral motor cortex. 2. A significant facilitation of short-latency peaks in the post-stimulus time histogram of single tibialis anterior motor units evoked by the transcortical magnetic stimulation was observed in eight out of nine subjects following stimulation of the superficial peroneal or sural nerves at the latency of the long-latency reflex. In contrast such a facilitation was only rarely seen when the medial plantar nerve was stimulated. 3. With the same timing for the stimuli, the superficial peroneal and sural nerve stimulations also produced a significant increase in the short-latency, presumed monosynaptic, facilitation of the tibialis anterior H reflex produced by the brain stimulation. 4. Similar facilitatory effects of the cutaneous stimuli could not be demonstrated when the magnetic stimulation of the cortex was replaced with electrical stimulation, implying that cortical excitability is affected by a conditioning cutaneous stimulation. 5. It is suggested that the long-latency reflexes in the tibialis anterior muscle evoked by activation of cutaneous afferents from the human foot are, at least partly, mediated by a transcortical pathway.

A quantitative polymerase chain reaction (PCR) method was used to measure the quantities of type I, IIa, IIx, and IIb myosin heavy chain (MHC) mRNA in total RNA preparations of the soleus, gastrocnemius, and plantaris muscles of normal and hindlimb-immobilized rats. Type IIx and even type IIb MHC mRNA were demonstrated at extremely low levels in normal soleus, 2.1 +/- 0.4 x 10(5) and 5.0 +/- 0.2 x 10(5) molecules of mRNA per microgram total RNA, respectively. Immobilization for 1 wk significantly altered the gene expression of MHC isoforms. In soleus, both type IIx and IIb MHC genes became significantly upregulated, 24-fold (P < 0.005) and 2.6-fold (P < 0.05), respectively. In gastrocnemius, the level of type IIa MHC mRNA decreased by 51% (P < 0.01) and the level of type IIx MHC mRNA increased by 140% (P < 0.05). In plantaris, the level of type IIa MHC mRNA decreased by 58% (P < 0.005). In conclusion, immobilization changed the MHC mRNA profile in three different types of skeletal muscle toward faster isoforms. The quantitative results permit reliable evaluation of changes in mRNA levels.

1. In resting subjects low-intensity magnetic stimulation of the brain evoked an inhibition of the soleus H reflex at short latency (conditioning-test interval, -2 to +1 ms) followed approximately 10 ms later by a period of facilitation. During voluntary dynamic or tonic plantar flexion the same stimulus evoked a facilitation with a shorter latency than the inhibition (conditioning-test interval, -5 to -1 ms). 2. At the onset of ramp-and-hold plantar flexion the short-latency facilitation was seen at lower intensities of stimulation than the long-latency facilitation in six of seven subjects. At rest and/or during tonic plantar flexion the opposite was observed in four of the subjects, whereas the two facilitations had approximately the same threshold in the remaining subjects. 3. The short-latency facilitation decreased approximately 100 ms after the onset of ramp-and-hold plantar flexion in all of eight subjects. The long-latency facilitation, in contrast, either had the same size throughout the ramp phase or even increased around the end of the ramp phase. 4. The short-latency facilitation of the reflex was significantly larger at the onset of a fast ramp-and-hold plantar flexion (10 N m (150 ms)-1) than at the onset of a slow contraction (10 N m (600 ms)-1), whereas the opposite was the case for the long-latency facilitation. 5. As the short- and long-latency facilitations had different thresholds and were differently regulated during voluntary movement, it is suggested that they are caused by activation of different descending pathways by the magnetic stimulus.