Corticospinal projections to lower limb motoneurons in man

Summary The projections of cortical neurons activated by transcranial magnetic stimulation to single lower limb spinal motoneurons were examined in 34 normal subjects. Peristimulus time histograms of the discharge times of single, voluntarily activated motor units were used to derive information about postsynaptic potentials in single spinal motoneurons produced by magnetic stimuli applied over the contralateral scalp. All tibialis anterior motor units and the majority of motoneurons innervating the small muscles of the foot showed strong short latency facilitation. About half of the motoneurons of proximal lower limb muscles showed this facilitation. Short latency facilitation of the motoneurons of soleus and medial gastrocnemius was only rarely observed and when present was weak. The short latency facilitation is attributed to the projections of the fast corticospinal pathway with monosynaptic projections to motoneurons. The relative strength of the facilitation in different motoneuron pools is considered to reflect the density of corticospinal projections to that motoneuron pool. The observed pattern of projections in man shows some differences from the pattern of projections in subhuman primates that might reflect the different use of the limb.     

Postnatal development of corticospinal postsynaptic action

The corticospinal system has a delayed and prolonged postnatal development. In the cat, lesion, inactivation, or stimulation of the system influence motor output minimally when corticospinal (CS) terminals have an immature topographic pattern but produce robust effects immediately after developing the mature pattern by weeks 6-7. In this study, we directly tested if the delay in expression of cortical motor functions is due to the inability of the corticospinal synapse to activate spinal neurons. We stimulated corticospinal axons in the pyramid and recorded evoked field potentials from the surface of the cervical spinal cord and locally from within the gray matter in anesthetized cats during development and in adults. Pyramidal stimulation in animals between week 4 and maturity evoked an initial corticospinal surface volley followed by a postsynaptic field response. Depth recordings from the superficial dorsal horn to the ventral white matter showed that local pre- and postsynaptic field potentials could be recorded over the full extent of the gray matter in 4- to 5-wk animals but were restricted to the intermediate zone in older animals and adults. Dorsoventral refinement of CS field potentials parallels anatomical refinement of individual CS axon terminals shown in our earlier studies. Our present findings indicate that the developing corticospinal system could influence the excitability of virtually the entire contralateral gray matter before cortical motor functions are expressed. Given the importance of activity-dependent axon terminal refinement, this capacity for activating spinal neurons during early postnatal life could play an important role in development of CS circuit connectivity.     

Mechanism of the silent period following transcranial magnetic stimulation Evidence from epidural recordings

We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50–200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357±62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability. Received: 21 January 1999 / Accepted: 14 April 1999     

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.     

Reduced intracortical inhibition and facilitation of corticospinal neurons in musicians

Interhemispheric inhibition between motor cortices is reduced in musicians. In the present study we have assessed intracortical inhibition (ICI) and facilitation (ICF) within ipsilateral motor cortex in 15 musicians and 15 non-musician controls. Transcranial magnetic stimulation (TMS) was used to elicit muscle evoked potentials (MEPs) from left first dorsal interosseous (FDI) muscle at rest, and during voluntary index finger abduction (0.5 N). Paired TMS with subthreshold conditioning was used to test early ICI with interstimulus intervals (ISIs) 1-5 ms, and ICF with ISIs 8-15 ms. Suprathreshold conditioning was used to test late ICI with ISIs 100-200 ms. TMS thresholds were similar in musicians and controls both at rest and with weak voluntary activation of FDI, indicating that postsynaptic excitability of corticospinal neurons was similar in both groups. ICI was less effective in musicians with FDI at rest and active, but only with an ISI of 3 ms. ICF was less effective in musicians under both rest and active conditions, and this was independent of ISI. There were no differences in late ICI between musicians and controls. We conclude that ICI and ICF circuits which are activated by weak TMS have less influence on corticospinal neuron excitability in musicians. Because of the dependence on ISI, the most likely explanation for the reduced ICI in musicians is an alteration of the interaction between the ICI circuit and neural elements responsible for the later I-waves evoked in corticospinal neurons by TMS. Excitability of the neural elements producing early and late ICI is not altered in musicians. Reduced ICF in musicians could be due to reduced excitability of neurons responsible for ICF, or an altered balance of excitatory inputs to corticospinal neurons which favours neurons that are not acted upon by the ICF circuit. The reduced influence of ICI and ICF circuits on corticospinal neuron excitability in musicians is likely to reflect a training-induced adaptation. It is not clear at present whether these differences represent an adaptive change related to their extraordinary control of finger movements, or alternatively a maladaptive change induced by "overuse" of the hands from extensive training.     

Characteristics of the output from the dentate nucleus to spinal neurons via pathways which do not involve the primary sensorimotor cortex

Summary Experiments were performed to determine the action of the dentate output on neurons in the spinal cord mediated by pathways which do not involve the primary sensorimotor and premotor cortices. The dentate nucleus was electrically stimulated by stereotaxically placed electrodes in Rhesus monkeys whose contralateral sensorimotor and premotor cortices were ablated. The resultant changes in excitability of lumbar alpha motoneurons activated by Ia afferents from nerves innervating femoral, hamstring, gastrocnemius-soleus and peroneal muscles were measured by intracellular recordings and by determining the percent change in the amplitude of the monosynaptic reflex recorded from ventral roots. The effect of stimulation of the dentate nucleus on proprioceptive reflexes was determined by recording the changes in postsynaptic potentials evoked by selective stimulation of Ia and Ib afferent fibers. The results demonstrated that the dentate nucleus exerts a significant action on the excitability of spinal neurons via pathways which do not include the sensorimotor and premotor cortices. Whether the dentate stimulus produced an increase or decrease in the excitability of these neurons was dependent upon the site within the dentate nucleus at which the stimulus was applied, demonstrating that, in the decorticate preparation, the output from this nucleus is quite heterogeneous. In addition, stimulation of the dentate nucleus in these monkeys did not affect the Ia reflex pathway but significantly changed the amplitude of the inhibitory postsynaptic potential evoked by Ib afferents in lumbar alpha motoneurons.     

Impaired crossed facilitation of the corticospinal pathway after cervical spinal cord injury

In uninjured humans, it is well established that voluntary contraction of muscles on one side of the body can facilitate transmission in the contralateral corticospinal pathway. This crossed facilitatory effect may favor interlimb coordination and motor performance. Whether this aspect of corticospinal function is preserved after chronic spinal cord injury (SCI) is unknown. Here, using transcranial magnetic stimulation, we show in patients with chronic cervical SCI (C(5)-C(8)) that the size of motor evoked potentials (MEPs) in a resting intrinsic hand muscle remained unchanged during increasing levels of voluntary contraction with a contralateral distal or proximal arm muscle. In contrast, MEP size in a resting hand muscle was increased during the same motor tasks in healthy control subjects. The magnitude of voluntary electromyography was negatively correlated with MEP size after chronic cervical SCI and positively correlated in healthy control subjects. To examine the mechanisms contributing to MEP crossed facilitation we examined short-interval intracortical inhibition (SICI), interhemispheric inhibition (IHI), and motoneuronal behavior by testing F waves and cervicomedullary MEPs (CMEPs). During strong voluntary contractions SICI was unchanged after cervical SCI and decreased in healthy control subjects compared with rest. F-wave amplitude and persistence and CMEP size remained unchanged after cervical SCI and increased in healthy control subjects compared with rest. In addition, during strong voluntary contractions IHI was unchanged in cervical SCI compared with rest. Our results indicate that GABAergic intracortical circuits, interhemispheric glutamatergic projections between motor cortices, and excitability of index finger motoneurons are neural mechanisms underlying, at least in part, the lack of crossed corticospinal facilitation observed after SCI. Our data point to the spinal motoneurons as a critical site for modulating corticospinal transmission after chronic cervical SCI.     

Organization of ipsilateral excitatory and inhibitory pathways in the human motor cortex

Motor cortex stimulation has both excitatory and inhibitory effects on ipsilateral muscles. Excitatory effects can be assessed by ipsilateral motor-evoked potentials (iMEPs). Inhibitory effects include an interruption of ipsilateral voluntary muscle activity known as the silent period (iSP) and a reduction in corticospinal excitability evoked by conditioning stimulation of the contralateral motor cortex (interhemispheric inhibition, IHI). Both iSP and IHI may be mediated by transcallosal pathways. Their relationship to the contralateral corticospinal projection and whether iSP and IHI represent the same phenomenon remain unclear. The neuronal population activated by transcranial magnetic stimulation (TMS) is highly dependent on the direction of the induced current in the brain. We examined the relationship among iMEP, iSP, IHI, and the contralateral corticospinal system by examining the effects of different stimulus intensities and current directions. Surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. The iSP in the right FDI muscle was obtained by right motor cortex stimulation during voluntary muscle contraction. IHI was examined by conditioning stimulation of the right motor cortex followed by test stimulation of the left motor cortex at interstimulus intervals (ISIs) of 2-80 ms. The induced current directions tested in the right motor cortex were anterior medial (AM), posterior medial (PM), posterior lateral, and anterior lateral (AL). Contralateral MEPs (cMEPs) had the lowest threshold with the AM direction and the shortest latency with the PM direction. iMEPs were present in 8 of 10 subjects. Both iMEP and IHI did not show significant directional preference. iSP was observed in all subjects with the highest threshold for the AL direction and the longest duration for the AM direction. cMEP, iSP, and IHI all increased with stimulus intensity up to approximately 75% stimulator output. Target muscle activation decreased IHI at 8-ms ISI but had little effect on IHI at 40-ms ISI. iSP and IHI at 8-ms ISI did not correlate at any stimulus intensities and current directions tested, and factor analysis showed that they are explained by different factors. However, active IHI at 40-ms ISI was explained by the same factor as iSP. The different directional preference for cMEP compared with iMEP and IHI suggests that these ipsilateral effects are mediated by populations of cortical neurons that are different from those activating the corticospinal neurons. iSP and IHI do not represent the same phenomenon and should be considered complementary measures of ipsilateral inhibition.     

Correlations between size parameters and the amplitude of the excitatory postsynaptic potential evoked by magnetic brain stimulation in human hand muscle motoneurons

According to the size principle for motoneurons one would expect that an excitatory stimulus given to a motoneuronal pool should evoke small excitatory postsynaptic potentials (EPSPs) in large and large EPSPs in small motoneurons of the pool. In this study this expectation was tested for the motoneuron pool of the first dorsal interosseus muscle of man excited by a magnetic stimulus given to the contralateral motor cortex. In total, 60 first dorsal interosseus motor units from three healthy volunteers were investigated. For each unit the EPSP size induced by the magnetic brain stimulus was assessed indirectly through a cross correlation of magnetic brain stimuli with motor unit discharges during a slight voluntary contraction. In addition to the indirect measurement of EPSP size, three indicators of motoneuronal size were obtained for each unit: the area the macroelectromyogram (Macro EMG) of the unit encloses with the baseline, the peak-to-peak amplitude of the Macro EMG, and the true latency from the magnetic stimulus to the motor unit which in turn provides an indirect estimate for the conduction velocity of the motoneuronal axon. It was found that all three measures of motoneuron size were significantly negatively correlated with the estimates of EPSP amplitude. Such significant negative correlations were found not only in the pooled data but also in the data from each subject individually. These correlations reveal that a magnetic brain stimulus induces small EPSPs in large and large EPSPs in small motoneurons of the first dorsal interosseus muscle of man.     

Corticospinal excitability during painful self-stimulation in humans: a transcranial magnetic stimulation study

We investigated changes in the corticospinal pattern of activity in healthy volunteers during sustained noxious and non-noxious mechanical stimulation of the first hand digit, resulting from active (self-stimulation) or passive (externally-induced) pressing against a sharp or blunted tip. The results indicate that, in order to press a finger onto a noxious stimulus with the same force generated to press onto a non-noxious one, the motor cortex adopts a peculiar strategy in terms of recruitment of motor units. This is reflected by an increase of corticospinal excitability (as revealed by motor potentials evoked by transcranial magnetic stimulation of the contralateral primary motor cortex) and EMG activity of agonist muscles, possibly related to an increase of motor unit synchronization.     

Output of human motoneuron pools to corticospinal inputs during voluntary contractions

This study investigated transmission of corticospinal output through motoneurons over a wide range of voluntary contraction strengths in humans. During voluntary contraction of biceps brachii, motor evoked potentials (MEPs) to transcranial magnetic stimulation of the motor cortex grow up to about 50% maximal force and then decrease. To determine whether the decrease reflects events at a cortical or spinal level, responses to stimulation of the cortex and corticospinal tract (cervicomedullary motor evoked potentials, CMEPs) as well as maximal M-waves (M(max)) were recorded during strong contractions at 50 to 100% maximum. In biceps and brachioradialis, MEPs and CMEPs (normalized to M(max)) evoked by strong stimuli decreased during strong elbow flexions. Responses were largest during contractions at 75% maximum and both potentials decreased by about 25% M(max) during maximal efforts (P < 0.001). Reductions were smaller with weaker stimuli, but again similar for MEPs and CMEPs. Thus the reduction in MEPs during strong voluntary contractions can be accounted for by reduced responsiveness of the motoneuron pool to stimulation. During strong contractions of the first dorsal interosseous, a muscle that increases voluntary force largely by frequency modulation, MEPs declined more than in either elbow flexor muscle (35% M(max), P < 0.001). This suggests that motoneuron firing rates are important determinants of evoked output from the motoneuron pool. However, motor cortical output does not appear to be limited at high contraction strengths.     

Impaired motor cortical inhibition in Parkinson's disease: motor unit responses to transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS)-induced corticospinal volleys can be investigated in detail by analysing the firing pattern modulation of active motor units (MUs) at close to threshold stimulation strengths. In amyotropic lateral sclerosis (ALS) these volleys are dispersed and prolonged, attributed to altered motor cortical excitability. Impaired intracortical inhibition, as found in ALS, is not unique to this disease, but is also a well-established finding in Parkinson's disease (PD). The present study explored whether reduced inhibition in the motor cortex in PD is accompanied by similar changes in motor unit firing modulation by TMS as are found in ALS. TMS was applied to the contralateral motor cortex during a low-force voluntary elbow flexion while 126-channel surface electromyography (SEMG) was recorded from the brachial biceps muscle. A recently developed method for SEMG decomposition was used to extract the firing pattern of up to five simultaneously active MUs. Sixteen MUs in 7 PD patients and 17 MUs in 5 healthy control subjects were analysed and peristimulus time histograms (PSTHs) and interspike interval change functions (IICFs) were calculated. The IICF provides an estimate of the modulation of the postsynaptic membrane potential at the spinal motoneuron, evoked by the stimulus. In PD the duration of the PSTH peak was significantly increased and the synchrony was decreased. The excitatory phase at 20–50 ms of the IICF was broader in PD, reflecting a longer duration of the TMS-evoked excitatory postsynaptic potential. It is proposed that these results are due to prolonged corticospinal volleys resulting from impaired intracortical inhibition. Electronic Publication     

Medullary reticulospinal tract mediating the generalized motor inhibition in cats: parallel inhibitory mechanisms acting on motoneurons and on interneuronal transmission in reflex pathways

The present study was designed to elucidate the spinal interneuronal mechanisms of motor inhibition evoked by stimulating the medullary reticular formation. Two questions were addressed. First, whether there is a parallel motor inhibition to motoneurons and to interneurons in reflex pathways. Second, whether the inhibition is mediated by interneurons interposed in known reflex pathways. We recorded the intracellular activity of hindlimb motoneurons in decerebrate cats and examined the effects of medullary stimulation on these neurons and on interneuronal transmission in reflex pathways to them. Stimuli (three pulses at 10-60microA and 1-10ms intervals) delivered to the nucleus reticularis gigantocellularis evoked inhibitory postsynaptic potentials in alpha-motoneurons (n=147) and gamma-motoneurons (n=5) with both early and late latencies. The early inhibitory postsynaptic potentials were observed in 66.4% of the motoneurons and had a latency of 4.0-5.5ms with a segmental delay of more than 1.4ms. The late inhibitory postsynaptic potentials were observed in 98.0% of the motoneurons and had a latency of 30-35ms, with a peak latency of 50-60ms. Both types of inhibitory postsynaptic potentials were evoked through fibers descending in the ventrolateral quadrant. The inhibitory postsynaptic potentials were not influenced by recurrent inhibitory pathways, but both types were greatly attenuated by volleys in flexor reflex afferents. Conditioning medullary stimulation, which was subthreshold to evoke inhibitory postsynaptic potentials in the motoneurons, neither evoked primary afferent depolarization of dorsal roots nor reduced the input resistance of the motoneurons. However, the conditioning stimulation often facilitated non-reciprocal group I inhibitory pathways (Ib inhibitory pathways) to the motoneurons in early (<20ms) and late (30-80ms) periods. In contrast, it attenuated test postsynaptic potentials evoked through reciprocal Ia inhibitory pathways, and excitatory and inhibitory pathways from flexor reflex afferent and recurrent inhibitory pathways. The inhibitory effects were observed in both early and late periods. The present results provide new information about a parallel inhibitory process from the medullary reticular formation that produces a generalized motor inhibition by acting on alpha- and gamma-motoneurons, and on interneurons in reflex pathways. Interneurons receiving inhibition from flexor reflex afferents and a group of Ib interneurons may mediate the inhibitory effects upon motoneurons.     

Unconscious modulation of motor cortex excitability revealed with transcranial magnetic stimulation

The neuronal effects of sensory events that do not enter conscious awareness have been reported in numerous pathological conditions and in normal subjects. In the present study, unconscious modulation of corticospinal excitability was probed in healthy volunteers with transcranial magnetic stimulation (TMS). TMS-induced motor evoked potentials (MEPs) were collected from the first dorsal interosseus muscle while subjects performed a masked semantic priming task that has been shown to elicit covert motor cortex activations. Our data show that the amplitude of the MEPs is modulated by an unseen prime, in line with temporal patterns revealed with event related potentials. These data confirm previous reports showing specific motor neural responses associated with an unseen visual stimulus and establish TMS as a valuable tool in the study of the neural correlates of consciousness.     

Influence of touching an object on corticospinal excitability during motor imagery

We investigated whether corticospinal excitability during the imagery of an action involving an external object was influenced by actually touching the object. Corticospinal excitability was assessed by monitoring motor evoked potentials (MEPs) in the first dorsal interosseous muscle following transcranial magnetic stimulation over the motor cortex during imagery of squeezing a ball—with or without passively holding the ball. The MEPs amplitude during imagery when the ball was held was larger than that when the ball was not held. The MEPs amplitude was not modulated just by holding the ball. In the same experimental condition, the somatosensory evoked potentials (SEPs) in response to the stimulation of median nerve were not modulated by motor imagery or by holding the ball. These results suggest that the corticospinal excitability during imagery of squeezing a ball is enhanced with the real touch of the ball, and the enhancement would be caused by some changes along the corticospinal pathway itself and not by the change in responsiveness along the afferent pathway to the primary somatosensory cortex.     

Inhibition of motoneurons during the cutaneous silent period in the spinal cord of the turtle

The transient suppression of motor activity in the spinal cord after a cutaneous stimulus is termed the cutaneous silent period (CSP). It is not known if CSP is due to suppression of the premotor network or direct inhibition of motoneurons. This issue was examined by intracellular recordings from motoneurons in the isolated carapace-spinal cord preparation from adult turtles during rhythmic scratch-like reflex. Electrical stimulation of cutaneous nerves induced CSP-like suppression of motor nerve firing during rhythmic network activity. The stimulus that generated the CSP-like suppression of motor activity evokes a polysynaptic compound synaptic potential in motoneurons and suppressed their firing. This compound synaptic potential was hyperpolarizing near threshold for action potentials and was associated with a substantial increase in conductance during the CSP in the motor pool. These results show that direct postsynaptic inhibition of motoneurons contributes to the CSP.     

Change in Excitability of Corticospinal Pathway and GABA-Mediated Inhibitory Circuits of Primary Motor Cortex Induced by Contraction of Adjacent Hand Muscle

The present study examined whether the excitability of the corticospinal pathway and the GABA-mediated inhibitory circuits of the primary motor cortex that project onto the corticospinal neurons in the tonically contracting hand muscle are changed by tonic contraction of the adjacent hand muscle. The motor evoked potential (MEP) and cortical silent period (CSP) in the tonically contracting hand muscle were obtained while the adjacent hand muscle was either tonically contracting or at rest. The MEP and CSP of the first dorsal interosseous (FDI) muscle elicited across the scalp sites where the MEP is predominantly elicited in the FDI muscle were decreased by tonic contraction of the abductor digiti minimi (ADM) muscle. The centers of the area of the MEP and the duration of the CSP in the FDI muscle elicited across the sites where the MEP is predominantly elicited in the FDI muscle were lateral to those in the FDI muscle elicited across the sites where the MEP is elicited in both the FDI and ADM muscles. They were also lateral to those in the ADM muscle elicited either across the sites where the MEP is predominantly elicited in the ADM muscle, or across the sites where the MEP is elicited in both the FDI and ADM muscles. The decrease in the corticospinal excitability and the excitability of the GABA-mediated inhibitory circuits of the primary motor cortex that project onto the corticospinal neurons in the FDI muscle may be due either to (1) the interaction between the activity of the lateral area of the FDI representation and the descending drive to the ADM muscle, or (2) the decreased susceptibility of the primary motor area that predominantly projects onto the corticospinal neurons in the FDI muscle, which also plays a role in independent finger movement when both the FDI and ADM muscles act together as synergists.     

Neural correlates of encoding and expression in implicit sequence learning

It has been shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) to the human primary motor hand area (M1-HAND) can induce a lasting increase in corticospinal excitability. Here we recorded motor evoked potentials (MEPs) from the right first dorsal interosseus muscle to investigate how sub-threshold high-frequency rTMS to the M1-HAND modulates cortical and spinal excitability. In a first experiment, we gave 1500 stimuli of 5 Hz rTMS. At an intensity of 90% of active motor threshold, rTMS produced no effect on MEP amplitude at rest. Increasing the intensity to 90% of resting motor threshold (RMT), rTMS produced an increase in MEP amplitude. This facilitatory effect gradually built up during the course of rTMS, reaching significance after the administration of 900 stimuli. In a second experiment, MEPs were elicited during tonic contraction using weak anodal electrical or magnetic test stimuli. 1500 (but not 600) conditioning stimuli at 90% of RMT induced a facilitation of MEPs in the contracting FDI muscle. In a third experiment, 600 conditioning stimuli were given at 90% of RMT to the M1-HAND. Using two well-established conditioning-test paradigms, we found a decrease in short-latency intracortical inhibition (SICI), and a facilitation of the first peak of facilitatory I-waves interaction (SICF). There was no correlation between the relative changes in SICI and SICF. These results demonstrate that subthreshold 5 Hz rTMS can induce lasting changes in specific neuronal subpopulations in the human corticospinal motor system, depending on the intensity and duration of rTMS. Short 5 Hz rTMS (600 stimuli) at 90% of RMT can selectively shape the excitability of distinct intracortical circuits, whereas prolonged 5 Hz rTMS (900 stimuli) provokes an overall increase in excitability of the corticospinal output system, including spinal motoneurones.     

Effect of tonic voluntary activity on the excitability of human motor cortex.

1. The threshold for obtaining EMG responses after transcranial magnetic stimulation of the brain is reduced by voluntary contraction of the target muscle. The present experiments tested whether some of this effect is due to increased cortical, as opposed to spinal, excitability during the contraction. 2. Magnetic stimulation was delivered with a figure-of-eight coil oriented with the junction region along the interaural line and also (in 4 of 7 subjects) with a circular coil centred at the vertex. The intensity of the conditioning stimulus was subthreshold for evoking a motor response in the relaxed wrist flexor muscles of the forearm. The presence of a small descending corticospinal volley in both the relaxed and active conditions was detected by measuring the facilitation of test H reflexes elicited in the flexor muscles of the forearm. 3. In all subjects, magnetic stimulation with either coil facilitated the H reflex at conditioning-test intervals of -1 to -3 ms (median nerve stimulus before magnetic). This was followed by a long-lasting facilitation. In three of the seven subjects stimulation with the figure-of-eight coil elicited an additional, earlier peak of facilitation at a conditioning-test interval of -3 to -5 ms. 4. In all subjects, the threshold for obtaining facilitation of the H reflex using a conditioning-test interval of -1 to -3 ms was reduced, and the amount of facilitation was larger, if subjects performed a weak tonic voluntary contraction. In contrast, with a conditioning-test interval of -3 to -5 ms voluntary contraction had no effect on the threshold. 5. It is suggested that H reflex facilitation at the conditioning-test interval of -1 to -3 ms was produced by indirect activation of corticospinal neurones by the magnetic stimulus, whereas at -3 to -5 ms, the facilitation was produced by direct activation of corticospinal axons. It is concluded that tonic voluntary contraction of a target muscle decreases the threshold for indirect activation of corticospinal neurones but not for direct stimulation of their axons.