2. TMS of low intensity (below threshold for a motor-evoked potential, MEP) produced a suppression of ongoing EMG activity during walking. The average latency for this suppression was 40·0 ± 1.0 ms. At slightly higher intensities of stimulation there was a facilitation of the EMG activity with an average latency of 29.5 ± 1.0 ms. As the intensity of the stimulation was increased the facilitation increased in size and eventually a MEP was clear in individual sweeps.3. In three subjects TMS was replaced by electrical stimulation over the motor cortex. Just below MEP threshold there was a clear facilitation at short latency (~28 ms). As the intensity of the electrical stimulation was reduced the size of the facilitation decreased until it eventually disappeared. We did not observe a suppression of the EMG activity similar to that produced by TMS in any of the subjects.4. The present study demonstrates that motoneuronal activity during walking can be suppressed by activation of intracortical inhibitory circuits. This illustrates for the first time that activity in the motor cortex is directly involved in the control of the muscles during human walking.

The cerebral activation during bicycle movements was investigated by oxygen-15-labelled H2O positron emission tomography (PET) in seven healthy human subjects. Compared to rest active bicycling significantly activated sites bilaterally in the primary sensory cortex, primary motor cortex (M1) and supplementary motor cortex (SMA) as well as the anterior part of cerebellum. Comparing passive bicycling movements with rest, an almost equal activation was observed. Subtracting passive from active bicycle movements, significant activation was only observed in the leg area of the primary motor cortex and the precuneus, but not in the primary sensory cortex (S1). The M1 activation was positively correlated (alpha=0.75-0.85, t=6.4, P<10(-5)) with the rate of the active bicycle movements. Imagination of bicycle movements compared to rest activated bilaterally sites in the SMA. It is suggested that the higher motor centres, including the primary and supplementary motor cortices as well as the cerebellum, take an active part in the generation and control of rhythmic motor tasks such as bicycling.

It is possible to obtain information about the synaptic drive to motoneurons during walking by analyzing motor-unit coupling in the time and frequency domains. The purpose of the present study was to compare motor-unit coupling during walking in healthy subjects and patients with incomplete spinal cord lesion to obtain evidence of differences in the motoneuronal drive that result from the lesion. Such information is of importance for development of new strategies for gait restoration. Twenty patients with incomplete spinal cord lesion (SCL) participated in the study. Control experiments were performed in 11 healthy subjects. In all healthy subjects, short-term synchronization was evident in the discharge of tibialis anterior (TA) motor units during the swing phase of treadmill walking. This was identified from the presence of a narrow central peak in cumulant densities constructed from paired EMG recordings and from the presence of significant coherence between these signals in the 10- to 20-Hz band. Such indicators of short-term synchrony were either absent or very small in the patient group. The relationship between the amount of short-term synchrony and the magnitude of the 10- to 20-Hz coherence in the patients is discussed in relation to gait ability. It is suggested that supraspinal drive to the spinal cord is responsible for short-term synchrony and coherence in the 10- to 20-Hz frequency band during walking in healthy subjects. Absence or reduction of these features may serve as physiological markers of impaired supraspinal control of gait in SCL patients. Such markers could have diagnostic and prognostic value in relation to the recovery of locomotion in patients with central motor lesions.

Pyndt, H. S. and J. B. Nielsen. Modulation of transmission in the corticospinal and group Ia afferent pathways to soleus motoneurons during bicycling. J Neurophysiol 89: 304 -314, 2003. 10.1152/jn.00386.2002. Transmission in the corticospinal and Ia pathways to soleus motoneurons was investigated in healthy human subjects during bicycling. Soleus H reflexes and motor evoked potentials (MEPs) after transcranial magnetic stimulation (TMS) were modulated similarly during the crank cycle being large during downstroke [concomitant with soleus background electromyographic (EMG) activity] and small during upstroke. Tibialis anterior MEPs were in contrast large during upstroke and small during downstroke. The soleus H reflexes and MEPs were also recorded during tonic plantarflexion at a similar ankle joint position, corresponding ankle angle, and matched background EMG activity as during the different phases of bicycling. Relative to their size during tonic plantarflexion, the MEPs were found to be facilitated in the early part of downstroke during bicycling, whereas the H reflexes were depressed in the late part of downstroke. The intensity of TMS was decreased below MEP threshold and used to condition the soleus H reflex. At short intervals (conditioning-test intervals of Ϫ3 to Ϫ1 ms), TMS produced a facilitation of the H reflex that is in all likelihood caused by activation of the fast monosynaptic corticospinal pathway. This facilitation was significantly larger in the early part of downstroke during bicycling than during tonic plantarflexion. This suggests that the increased MEP during downstroke was caused by changes in transmission in the fast monosynaptic corticospinal pathway. To investigate whether the depression of H reflexes in the late part of downstroke was caused by increased presynaptic inhibition of Ia afferents, the soleus H reflex was conditioned by stimulation of the femoral nerve. At a short interval (conditioning-test interval: Ϫ7 to Ϫ5 ms), the femoral nerve stimulation produced a facilitation of the H reflex that is mediated by the heteronymous monosynaptic Ia pathway from the femoral nerve to soleus motoneurons. Within the initial 0.5 ms after its onset, the size of this facilitation depends on the level of presynaptic inhibition of the Ia afferents, which mediate the facilitation. The size of the facilitation was strongly depressed in the late part of downstroke, compared with the early part of downstroke, suggesting that increased presynaptic inhibition was indeed responsible for the depression of the H reflex. These findings suggest that there is a selectively increased transmission in the fast monosynaptic corticospinal pathway to soleus motoneurons in early downstroke during bicycling. It would seem likely that one cause of this is increased excitability of the involved cortical neurons. The increased presynaptic inhibition of Ia afferents in late downstroke may be of importance for depression of stretch reflex activity before and during upstroke.

In this review we discuss the contribution of transcranial magnetic stimulation (TMS) to the understanding of human motor control. Compound motor-evoked potentials (MEPs) may provide valuable information about corticospinal transmission, especially in patients with neurological disorders, but generally do not allow conclusions regarding the details of corticospinal function to be made. Techniques such as poststimulus time histograms (PSTHs) of the discharge of single, voluntarily activated motor units and conditioning of H reflexes provide a more optimal way of evaluating transmission in specific excitatory and inhibitory pathways. Through application of such techniques, several important issues have been clarified. TMS has provided the first real evidence that direct monosynaptic connections from the motor cortex to spinal motoneurons exist in man, and it has been revealed that the distribution of these projections roughly follows the same proximal-distal gradient as in other primates. However, pronounced differences also exist. In particular, the tibialis anterior muscle appears to receive as significant a monosynaptic corticospinal drive as muscles in the hand. The reason for this may be the importance of this muscle in controlling the foot trajectory in the swing phase of walking. Conditioning of H reflexes by TMS has provided evidence of changes in cortical excitability prior to and during various movements. These experiments have generally confirmed information obtained from chronic recording of the activity of corticospinal cells in primates, but information about the corticospinal contribution to movements for which information from other primates is sparse or lacking has also been obtained. One example is walking, where TMS experiments have revealed that the corticospinal tract makes an important contribution to the ongoing EMG activity during treadmill walking. TMS experiments have also documented the convergence of descending corticospinal projections and peripheral afferents on spinal interneurons. Current investigations of the functional significance of this convergence also rely on TMS experiments. The general conclusion from this review is that TMS is a powerful technique in the analysis of motor control, but that care is necessary when interpreting the data. Combining TMS with other techniques such as PSTH and H reflex testing amplifies greatly the power of the technique.

The purpose of this study was to investigate the role of reciprocal inhibition in the regulation of antagonistic ankle muscles during bicycling. A total of 20 subjects participated in the study. Reciprocal inhibition was induced by stimulation of the peroneal nerve (PN) at 1.2 times threshold for the M-response in the tibialis anterior muscle (TA) and recorded as a depression of the rectified soleus (SOL) EMG. Recordings were made during tonic plantar flexion and during bicycling on an ergometer bicycle. During tonic contraction, the amount of inhibition in the SOL EMG was linearly correlated to the amount of background EMG. This linear relation was used to calculate the expected amount of reciprocal inhibition at corresponding EMG levels during bicycling. During the early phase of down-stroke of bicycling at 60 revolutions per minute (RPM) and an external load of 1.0 kg, the amount of recorded reciprocal inhibition was significantly smaller than that calculated from the linear relation during tonic contraction. In nine subjects, the SOL H-reflex was used to evaluate the amount of inhibition. At a short conditioning test interval (2-3 ms), the PN stimulation depressed the SOL H-reflex when the subjects were at rest. This short latency inhibition was absent during downstroke, but appeared during upstroke just prior to and during TA activation. A positive linear relation was found between the level of SOL background EMG in early downstroke and the external load (0.5-2.5 kg) as well as the rate of pedaling (30-90 RPM at 1.0 kg external load). The amount of inhibition in the SOL EMG when expressed as a percentage of the background EMG activity decreased significantly with increasing load. During increased pedaling rate, a similar decrease was seen, but it did not reach a statistically significant level. The data illustrate that reciprocal inhibition of the soleus muscle is modulated during bicycling being small in downstroke when the SOL muscle is active and large in upstroke where the muscle is inactive and its antagonist becomes active. The depression of the inhibition in relation to increased load and pedaling rate likely reflects the need of reducing inhibition of the SOL motoneurons to ensure a sufficient activation of the muscle.

Manipulation of afferent input is capable of inducing reorganisation of the motor cortex. For example, following 1 h of paired electrical stimulation to the motor point of two hand muscles ("associative stimulation") the excitability of the corticospinal projection to the stimulated muscles is increased. Here we investigated the mechanisms responsible for such change using transcranial magnetic stimulation (TMS). Cortical excitability changes were investigated by measuring motor evoked potentials (MEPs), intracortical inhibition (ICI), intracortical facilitation (ICF), and short-interval intracortical facilitation (SICF). Following 1 h of associative stimulation MEP amplitudes in the stimulated muscles significantly increased. Additionally, there was a significant increase in ICF and of SICF at interstimulus intervals in the range of 2.3-3.3 ms. There was no significant change in ICI. These findings confirm previous observations that a 1-h period of associative stimulation can increase the excitability of the cortical projection to stimulated muscles. Additionally, these results suggest that the observed modifications of excitability are due to changes in intracortical excitatory circuits.