Task-dependent modulation of inhibitory actions within the primary motor cortex

 In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205±42 ms; FDI 213±47 ms). SP duration at tonic isometric contraction amounted to 172±35 ms in APB and 178±31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159±15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies –30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex. Received: 24 November 1997 / Accepted: 11 August 1998     

Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects

The aim of this study was to determine whether prolonged, repetitive mixed nerve stimulation (duty cycle 1 s, 500 ms on-500 ms off, 10 Hz) of the ulnar nerve leads to a change in excitability of primary motor cortex in normal human subjects. Motor-evoked potentials (MEPs) generated in three intrinsic hand muscles [abductor digiti minimi (ADM), first dorsal interosseous (FDI) and abductor pollicis brevis (APB)] by focal transcranial magnetic stimulation were recorded during complete relaxation before and after a period of prolonged repetitive ulnar nerve stimulation at the wrist. Transcranial magnetic stimuli were applied at seven scalp sites separated by 1 cm: the optimal scalp site for eliciting MEPs in the target muscle (FDI), three sites medial to the optimal site and three sites lateral to the optimal stimulation site. The area of the MEPs evoked in the ulnar-(FDI, ADM) but not the median-innervated (APB) muscles was increased after prolonged ulnar nerve stimulation. Centre of gravity measures demonstrated that there was no significant difference in the distribution of cortical excitability after the peripheral stimulation. F-wave responses in the intrinsic hand muscles were not altered after prolonged ulnar nerve stimulation, suggesting that the changes in MEP areas were not the result of stimulus-induced increases in the excitability of spinal motoneurones. Control experiments employing transcranial electric stimulation provided no evidence for a spinal origin for the excitability changes. These results demonstrate that in normal human subjects the excitability of the cortical projection to hand muscles can be altered in a manner determined by the peripheral stimulus applied.     

Long-lasting modulation of human motor cortex following prolonged transcutaneous electrical nerve stimulation (TENS) of forearm muscles: evidence of reciprocal inhibition and facilitation

Several lines of evidence indicate that motor cortex excitability can be modulated by manipulation of afferent inputs, like peripheral electrical stimulation. Most studies in humans mainly dealt with the effects of prolonged low-frequency peripheral nerve stimulation on motor cortical excitability, despite its being known from animal studies that high-frequency stimulation can also result in changes of the cortical excitability. To investigate the possible effects of high-frequency peripheral stimulation on motor cortical excitability we recorded motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex from the right flexor carpi radialis (FCR), extensor carpi radialis (ECR), and first dorsal interosseous (FDI) in normal subjects, before and after transcutaneous electrical nerve stimulation (TENS) of 30 min duration applied over the FCR. The amplitude of MEPs from the FRC was significantly reduced from 10 to 35 min after TENS while the amplitude of MEPs from ECR was increased. No effects were observed in the FDI muscle. Indices of peripheral nerve (M-wave) and spinal cord excitability (H waves) did not change throughout the experiment. Electrical stimulation of the lateral antebrachial cutaneous nerve has no significant effect on motor cortex excitability. These findings suggest that TENS of forearm muscles can induce transient reciprocal inhibitory and facilitatory changes in corticomotoneuronal excitability of forearm flexor and extensor muscles lasting several minutes. These changes probably may occur at cortical site and seem to be mainly dependent on stimulation of muscle afferents. These findings might eventually lead to practical applications in rehabilitation, especially in those syndromes in which the excitatory and inhibitory balance between agonist and antagonist is severely impaired, such as spasticity and dystonia.M. Tinazzi and S. Zarattini contributed equally to the work     

Suppression of the motor cortex by magnetic stimulation of the cerebellum

Conditioning magnetic stimulation of the cerebellum suppresses the motor cortex 5-8 ms later, probably through activation of cerebellar Purkinje cells, which inhibit the dentatothalamocortical pathway. To further characterize this pathway, we examined several factors that may modulate its excitability. We tested the effects of different test motor evoked potential (MEP) amplitudes, voluntary activation of the target muscle, and arm extension that required activation of proximal arm muscles while maintaining relaxation of hand muscles. Surface electromyography was recorded from the right first dorsal interosseous (FDI) muscle. A double-cone coil centered 3 cm lateral to the inion was used for right cerebellar stimulation. The stimulus intensity was set at 5% below the threshold for activation of the corticospinal tract. A figure-of-eight coil was used for left motor cortex stimulation. Interstimulus intervals (ISIs) between 3 and 15 ms were studied. Small test MEPs of about 0.5 mV were markedly inhibited at ISIs of 5-8 ms, but there was much less inhibition for test MEPs of about 2 mV. There was no significant MEP suppression during voluntary activation of the FDI muscle or during right arm extension. Left arm extension did not affect inhibition. Our findings indicate that cerebellar stimulation has a much stronger effect on motor cortex neurons activated near threshold intensities than those activated at higher intensities. Activation of contralateral but not ipsilateral proximal arm muscles during arm extension reduced the excitability of the cerebellothalamocortical projections to the hand area of the motor cortex.     

Role of the human motor cortex in rapid motor learning

Recent studies suggest that the human primary motor cortex (M1) is involved in motor learning, but the nature of that involvement is not clear. Here, learning-related changes in M1 excitability were studied with transcranial magnetic stimulation (TMS) while na subjects practiced either a ballistic or a ramp pinch task to the 0.5-Hz beat of a metronome. Subjects rapidly learned to optimize ballistic contractions as indicated by a significant increase in peak pinch acceleration and peak force after the 60-min practice epoch. The increase in force and acceleration was associated with an increase in motor evoked potential (MEP) amplitude in a muscle involved in the training (flexor policis brevis) but not in a muscle unrelated to the task (abductor digiti minimi). MEPs returned to their baseline amplitude after subjects had acquired the new skill, whereas no practice-induced changes in MEP amplitude were observed after subjects had overlearned the task, or after practicing slow ramp pinches. Since the changes in MEP amplitude were observed only after TMS of M1 but not after direct stimulation of the corticospinal tract, these findings indicate task- and effector-specific involvement of human M1 in rapid motor learning.     

Modification of the human motor cortex by associative stimulation

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.     

Modulation of intracortical facilitatory circuits of the human primary motor cortex by digital nerve stimulation

We investigated the effect of electrical digit stimulation on two different intracortical facilitatory phenomena. Paired-pulse transcranial magnetic stimuli (TMS) with different conditioning stimulus (CS) intensities were applied over the primary motor cortex (M1). Electromyographic (EMG) recordings were made from the relaxed right abductor digiti minimi muscle (ADM). The effect of preceding sensory stimulation applied to the ipsilateral digit V on the conditioning magnetic stimulus was examined. Changing the CS intensity affected the influence of peripheral electrical stimulation on motor evoked potential (MEP) amplitudes evoked by paired pulse TMS. Inhibition induced by ipsilateral digit stimulation was strongest with the lowest CS intensity if MEP amplitudes were evoked by a subthreshold CS followed by a suprathreshold test stimulus (TS) at an interstimulus interval (ISI) of 10 ms. In contrast, inhibition induced by digit stimulation in a paired-pulse paradigm with a suprathreshold first and a subthreshold second stimulus at ISI of 1.5 ms was strongest with the highest CS intensity. These findings suggest that appropriately timed peripheral electrical stimuli differentially modulate facilitatory interactions in the primary motor cortex. They further support the hypothesis that intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) are evoked through different mechanisms. An erratum to this article can be found at     

Transcallosally mediated inhibition of interneurons within human primary motor cortex

The objective of this study was to investigate interhemispheric transcallosal connections between primary motor cortices noninvasively in awake human subjects. For this purpose, focal transcranial magnetic stimulation was performed on eight healthy, right-handed subjects and one patient with congenital collosal agenesis. Using two magnetic stimulators, we investigated the effect of a conditioning magnetic stimulus applied to the motor cortex of one hemisphere on the duration of the silent period (SP) evoked in the first dorsal interosseus (FDI) muscle by a magnetic test stimulus given over the opposite motor cortex. It is well established that SP reflects activation of inhibitory interneurons within primary motor cortex. In all normal subjects, a conditioning stimulus to one hemisphere produced a significant shortening of SP evoked by the test stimulus when the conditioningtest-interval was 10–20 ms. The effect was also observed when an electrical test stimulus was used. The conditioning coil had to be placed over the hand motor area to obtain the maximal effect. The threshold for eliciting this decrease of SP duration was higher than the threshold for eliciting an early excitatory muscle response in the contralateral FDI. Increasing the intensity of the conditioning stimulus led to linear reduction of SP duration. In the patient with callosal agenesis, no such decreasing effect on SP duration was observed. These results suggest that inhibitory interneurons within primary hand motor cortex receive transcallosal inhibitory input from the opposite motor cortex. We propose that modulation of motor cortical interneurons via transcallosal pathways may provide a gain control for the motor cortical output system and subserve interhemispheric coordination in complex, nonsymmetrical bimanual movements.     

Transcranial magnetic stimulation of the primary motor cortex modulates response interference in a flanker task

In a typical flanker task, responses to a central target (“S” or “N”) are modulated by whether the flankers are compatible (“SSSSS”) or incompatible (“NNSNN”), with increased reaction times and decreased accuracy on incompatible trials. The role of the motor system in response interference under these conditions remains unclear, however. Here we show that transcranial magnetic stimulation (TMS) of the left primary motor cortex modulates the amount of flanker interference depending on the hand used for the response. Left motor TMS delivered at 200 ms after the onset of the array increased interference from incompatible flankers (“SSNSS”) when the target response was associated with the contralateral motor response (i.e. for “N” responses with the right hand), relative to when responses were to targets using the (left) hand ipsilateral to the site of TMS. Interestingly, under identical conditions, the degree of flanker interference was reduced when the TMS pulse was applied later in time. The analyses of the TMS-induced motor evoked potentials pointed to motor activity varying in the same conditions. We discuss the implications for understanding response interference and the role of the primary motor cortex in response selection.     

Further evidence to support different mechanisms underlying intracortical inhibition of the motor cortex

Paired-pulse magnetic stimulation has been widely used to study intracortical inhibition of the motor cortex. Inhibition at interstimulus intervals (ISIs) of 1–5 ms is ascribed to a GABAergic inhibitory system in the motor cortex. However, Fisher et al. have proposed that different mechanisms are operating at an ISI of 1 ms and 2.5 ms. In order to confirm their concept and clarify whether inhibition at all these intervals is produced by a single mechanism, we compared effects of paired-pulse stimulation at ISIs of 1 ms, 2 ms, and 3–5 ms. We evaluated how intracortical inhibition affected the I3-wave, I1-wave, magnetic D-wave, and anodal D-wave components of electromyographic (EMG) responses using previously reported methods. The data suggest that three separate effects occur within these ISIs. At ISIs of 3–5 ms, inhibition was evoked only in responses to I3-waves, whereas no inhibition was elicited in responses to I1-waves or magnetic D-waves. In contrast, at an ISI of 1 ms, responses to I3-waves and I1-waves were moderately suppressed. Moreover, even magnetic D-waves were slightly suppressed, whereas anodal D-waves were unaffected. At an ISI of 2 ms, none of the descending volleys were inhibited. We propose that we should use ISIs of 3–5 ms for estimating function of the GABAergic inhibitory system of the motor cortex by paired-pulse transcranial magnetic stimulation (TMS). Our results support the idea of Fisher et al. that the mechanism responsible for the inhibition at an ISI of 1 ms is not the same as that responsible for suppression at ISIs of 3–5 ms (GABAergic inhibitory circuits in the motor cortex). At an ISI of 2 ms, we suggest that the inhibitory influence evoked by the first stimulus (S1) should collide with or be occluded by the second stimulus (S2), which leads to the lack of inhibition when the subjects make a voluntary contraction of the target muscle.     

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.     

Significance of shape and size of the stimulating coil in magnetic stimulation of the human motor cortex

Three different stimulating coil designs were evaluated for magnetic motor cortex stimulation by comparing threshold stimulus intensities at different sites over the scalp for exciting upper and lower limb muscles. Little difference was found between stimulation characteristics of two circular coils of different size, the smaller coil delivering slightly more focal stimuli. A twin coil composed of two single circular coils in series arranged side-by-side, produced significantly more powerful and more focal stimuli. It proved to be superior for exciting the leg muscles, in that less output energy was needed. For all coils, the orientation of the inducing current over the presumed motor area was the most critical stimulation parameter, and a sagittal current in anterior direction or coronal towards the stimulated hemisphere was optimal for the upper limb or lower limb muscles, respectively.     

Modulation of motor cortex excitability by median nerve and digit stimulation

We investigated the time course of changes in motor cortex excitability after median nerve and digit stimulation. Although previous studies showed periods of increased and decreased corticospinal excitability following nerve stimulation, changes in cortical excitability beyond 200 ms after peripheral nerve stimulation have not been reported. Magnetoencephalographic studies have shown an increase in the 20-Hz rolandic rhythm from 200 to 1000 ms after median nerve stimulation. We tested the hypothesis that this increase is associated with reduced motor cortex excitability. The right or left median nerve was stimulated and transcranial magnetic stimulation (TMS) was applied to left motor cortex at different conditioning-test (C-T) intervals. Motor-evoked potentials (MEPs) were recorded from the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), and extensor carpi radialis (ECR) muscles. Right median nerve stimulation reduced test MEP amplitude at C-T intervals from 400 to 1000 ms for APB, at C-T intervals from 200 to 1000 ms for FDI, and at C-T intervals of 200 and 600 ms for ECR, but had no effect on FDI F-wave amplitude at a C-T interval of 200 ms. Left median nerve (ipsilateral to TMS) stimulation resulted in less inhibition than right median nerve stimulation, but test MEP amplitude was significantly reduced at a C-T interval of 200 ms for all three muscles. Digit stimulation also reduced test MEP amplitude at C-T intervals of 200–600 ms. The time course for decreased motor cortex excitability following median nerve stimulation corresponds well to rebound of the 20-Hz cortical rhythm and supports the hypothesis that this increased power represents cortical deactivation. Received: 11 December 1998 / Accepted: 30 April 1999     

Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation

Ten healthy subjects and two patients who had an electrode implanted into the cervical epidural space underwent repetitive transcranial magnetic stimulation (rTMS; 50 stimuli at 5 Hz at active motor threshold intensity) of the hand motor area. We evaluated intracortical inhibition before and after rTMS. In healthy subjects, we also evaluated threshold and amplitude of motor evoked potentials (MEPs), duration of cortical silent period and short-latency intracortical facilitation. rTMS led to a short-lasting reduction in the amount of intracortical inhibition in control subjects with a high interindividual variability. There was no significant effect on other measures of motor cortex excitability. Direct recordings of descending corticospinal volleys from the patients were consistent with the idea that the effect of rTMS on intracortical inhibition occurred at the cortical level. Since the level of intracortical inhibition can be influenced by drugs that act on GABAergic systems, this may mean that low-intensity repetitive magnetic stimulation at 5 Hz can selectively modify the excitability of GABAergic networks in the human motor cortex. Electronic Publication     

Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex

The aim of the present study was to investigate whether muscarinic receptor blockade with scopolamine modifies the excitability of specific cortical networks of the human motor cortex as tested with transcranial magnetic stimulation. The effects of scopolamine on the excitability of human motor cortex were investigated in four healthy subjects using transcranial magnetic stimulation before and after an intravenous dose of scopolamine (0.006 mg/kg). We measured the threshold for motor responses, amplitude of motor responses, the duration of the cortical silent period, intracortical inhibition and facilitation, and short-latency inhibition produced by somatosensory input from the hand. In addition, we evaluated the amplitude of motor responses evoked by electrical anodal stimulation, since these responses originate from direct activation of corticospinal axons in the white matter and are not sensitive to changes in cortical excitability. Scopolamine decreased the threshold to magnetic stimuli and increased the amplitude of motor responses evoked by magnetic stimulation. In contrast, motor responses evoked by electrical stimulation were unaffected by administration of scopolamine. Scopolamine also led to a highly significant reduction in the amount of short-latency inhibition produced by somatosensory input from the hand. In contrast, short-latency intracortical inhibition and facilitation were not modified by scopolamine. The differential effect of scopolamine on motor responses evoked by magnetic and electrical stimulation of the motor cortex and the selective effect on somatosensory inhibition demonstrate that muscarinic blockade modifies the excitability of specific cortical networks in the human motor cortex.     

Changes in the cortical silent period after repetitive magnetic stimulation of cortical motor areas

Behavioral experiments were conducted to examine the role of the cholinergic receptor-agonist muscarine or its antagonist homatropine on the mating behavior of sexually experienced male rats. Male copulatory behavior was recorded after intrathecally administered saline, muscarine (7.5 μg), or homatropine (25 μg). Changes in copulatory behavior were assessed by the following parameters: intromission latency, intromission frequency, intercopulatory interval, ejaculation latency, and postejaculatory interval. Intromission frequency, intercopulatory interval, and ejaculation latency were decreased significantly by muscarine. Intrathecal homatropine decreased the number of copulating animals (five out of 13). In the five animals that were able to ejaculate after homatropine, intromission latency, intercopulatory interval, and ejaculation latency increased significantly. The effects of both drugs on locomotion were also tested. Muscarine induced no significant changes in locomotion compared with saline. A significant increase in locomotion was found after homatropine treatment. These results suggest that acetylcholine, acting at spinal-cord muscarinic receptors, may be involved in ejaculation. Electronic Publication     

Direct demonstration of interhemispheric inhibition of the human motor cortex produced by transcranial magnetic stimulation

 Electromyographic (EMG) responses evoked in hand muscles by a magnetic test stimulus over the motor cortex can be suppressed if a conditioning stimulus is applied to the opposite hemisphere 6–30 ms earlier. In order to define the mechanism and the site of action of this inhibitory phenomenon, we recorded descending volleys produced by the test stimulus through high cervical, epidural electrodes implanted for pain relief in three conscious subjects. These could be compared with simultaneously recorded EMG responses in hand muscles. When the test stimulus was given on its own it evoked three waves of activity (I-waves) in the spinal cord, and a small EMG response in the hand. A prior conditioning stimulus to the other hemisphere suppressed the size of both the descending spinal cord volleys and the EMG responses evoked by the test stimulus when the interstimulus interval was greater than 6 ms. In the spinal recordings, the effect was most marked for the last I-wave (I₃), whereas the second I₂-wave was only slightly inhibited, and the first I-wave (I₁) was not inhibited at all. We conclude that transcranial stimulation over the lateral part of the motor cortex of one hemisphere can suppress the excitability of the contralateral motor cortex. Received: 31 August 1998 / Accepted: 26 October 1998     

Effects of 5 Hz subthreshold magnetic stimulation of primary motor cortex on fast finger movements in normal subjects

We evaluated the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on motor performance and motor learning of a rapid index finger movement. Two groups of healthy right-handed subjects underwent either “real” rTMS (1800 stimuli over the first dorsal interosseous (FDI) muscle hot spot given at 5 Hz and intensity of 90% of resting motor threshold—RMT) or “sham” stimulation. Both groups performed 60 rapid abductions of the right index finger before and after rTMS. The kinematic variables measured were amplitude, duration, peak velocity and peak acceleration. We also evaluated RMT and motor-evoked potential (MEP) amplitude before, 5 and 30 min after rTMS. In both groups practice significantly increased peak velocity, peak acceleration and amplitude and decreased movement duration independently from the type of intervention (“real” and “sham”). “Real” rTMS significantly increased cortical excitability as measured by MEP amplitude whereas “sham” rTMS did not. In our study, 5 Hz rTMS failed to improve either the motor performance or the motor learning of a rapid index-finger abduction despite the increase in cortical excitability of the primary motor cortex. Since motor behaviour engages a distributed cortical and subcortical neuronal network, excitatory conditioning of the primary motor cortex is probably not sufficient to influence the behavioural output.     

Task-dependent control of human masseter muscles from ipsilateral and contralateral motor cortex

Corticotrigeminal projections to human masseter motoneuron pools were investigated with focal transcranial magnetic stimulation (TMS). Responses in left and right masseter muscles were quantified from the surface electromyogram (EMG) during different biting tasks. During bilateral biting, TMS elicited motor evoked potentials (MEPs) in both masseter muscles. On average, the MEP area in the masseter contralateral to the stimulus was 39% larger than in the ipsilateral muscle, despite comparable pre-stimulus EMG in both muscles. MEPs elicited while subjects attempted unilateral activation of one masseter muscle were compared with those obtained in the same muscle during a bilateral bite at an equivalent EMG level. MEPs in the masseter contralateral to the stimulated hemisphere were significantly smaller during unilateral compared with bilateral biting. There was no significant difference in the size of ipsilateral MEPs during ipsilateral and bilateral biting. We conclude that the corticotrigeminal projections to masseter are bilateral, with a stronger contralateral projection. The command for unilateral biting is associated with a reduced excitability of corticotrigeminal neurons in the contralateral, but not the ipsilateral motor cortex. We suggest that this may be accomplished by reduced activity of a population of corticotrigeminal neurons which branch to innervate both masseter motoneuron pools.     

Remote effects of self-paced teeth clenching on the excitability of hand motor area

We studied remote effects of teeth clenching on motor cortical and spinal cord excitability using transcranial magnetic stimulation (TMS), brainstem electrical stimulation (BES), and ulnar nerve stimulation (F-wave) in eight normal volunteers. The TMS, BES, and ulnar nerve stimulation at the wrist were given at different intervals (0–200 ms) after the onset of masseter contraction. Surface electromyographic responses were recorded from the first dorsal interosseous muscle. Responses at different intervals were compared with the response elicited when the subject made no teeth clenching (control response). In TMS, conditioned responses (during teeth clenching) were significantly larger than the control at all intervals. In contrast, in BES and F-waves, conditioned responses were not larger than the control at an early phase (intervals shorter than 50 ms), whereas they were larger than the control at later intervals (longer than 50 ms). These results suggest that facilitation occurs in the hand motor area at the early phase of teeth clenching, and spinal facilitation dominates at its late phase. This time course of facilitation may indicate that the motor cortex must regulate hand muscles finely at the early phase of teeth clenching, and spinal cord may stabilize them firmly at the late phase. The excitability changes of the hand motor area may be in parallel with that of the masseter motor area which reflects the pattern of masseter contraction when the subject activates the masseter muscle phasically at the early phase and sustains that contraction at the late phase. Electronic Publication