Modulation of motor cortex excitability after upper limb immobilization.

OBJECTIVE: To examine the mechanisms of disuse-induced plasticity following long-term limb immobilization. METHODS: We studied 9 subjects, who underwent left upper limb immobilization for unilateral wrist fractures. All subjects were examined immediately after splint removal. Cortical motor maps, resting motor threshold (RMT), motor evoked potential (MEP) latency and MEP recruitment curves were studied from abductor pollicis brevis (APB) and flexor carpi radialis (FCR) muscles with single pulse transcranial magnetic stimulation (TMS). Paired pulse TMS was used to study intracortical inhibition and facilitation. Compound muscle action potentials (CMAPs) and F waves were obtained after median nerve stimulation. In 4/9 subjects the recording was repeated after 35-41 days. RESULTS: CMAP amplitude and RMT were reduced in APB muscle on the immobilized sides in comparison to the non-immobilized sides and controls after splint removal. CMAP amplitude and RMT were unchanged in FCR muscle. MEP latency and F waves were unchanged. MEP recruitment was significantly greater on the immobilized side at rest, but the asymmetry disappeared during voluntary muscle contraction. Paired pulse TMS showed an imbalance between inhibitory and excitatory networks, with a prevalence of excitation on the immobilized sides. A slight, non-significant change in the strength of corticospinal projections to the non-immobilized sides was found. TMS parameters were not correlated with hand dexterity. These abnormalities were largely normalized at the time of retesting in the four patients who were followed-up. CONCLUSIONS: Hyperexcitability occurs within the representation of single muscles, associated with changes in RMT and with an imbalance between intracortical inhibition and facilitation. These findings may be related to changes in the sensory input from the immobilized upper limb and/or in the discharge properties of the motor units. SIGNIFICANCE: Different mechanisms may contribute to the reversible neuroplastic changes, which occur in response to long-term immobilization of the upper-limbs.     

Nonspecific facilitation of responses to transcranial magnetic stimulation.

We examined the effect of facial muscle contraction and eye movements on motor evoked potentials (MEPs) from the abductor pollicis brevis muscle (APB) evoked by transcranial magnetic stimulation (TMS). The hypothesis was that activity of large cortical regions (face) influences the excitability of spinal motoneurons via cortical or subcortical pathways. MEPs were recorded in 12 healthy subjects during the following conditions: (1) rest; (2) facial muscle contraction; (3) eye movements; (4) 10% precontraction of the target muscle; and (5) simultaneous target muscle precontraction and facial muscle contraction. In 9 subjects, spinal motoneuron excitability was assessed by measurements of F waves during the same facilitation maneuvers. Activation of eye and facial muscles clearly facilitated MEPs from the APB. The facilitation of MEP size during nonspecific maneuvers was almost similar to that obtained by target muscle precontraction, whereas shortening of latencies was significantly smaller. The occurrence and amplitude of F waves increased in parallel with MEP size during specific and nonspecific facilitation, pointing to spinal motoneuronal threshold changes as a potential facilitatory mechanism by facial and eye muscle activation. The different MEP latencies during specific and nonspecific facilitation were not explained by different spinal motoneuron excitability, but raise the possibility that supraspinal mechanisms contributed to nonspecific facilitation.     

Transcranial magnetic stimulation reduces masseter motoneuron pool excitability throughout the cortical silent period.

OBJECTIVE: To evaluate the time-course of changes in masseter motoneuron pool excitability following transcranial magnetic stimulation of motor cortex, and relate this to the duration of the masseter cortical silent period (CSP). METHODS: Surface EMG was recorded bilaterally from masseter and digastric muscles in 13 subjects. Focal TMS was applied at 1.3x active motor threshold (AMT) to motor cortex of one hemisphere to elicit a muscle evoked potential (MEP) and silent period bilaterally in masseter as subjects maintained an isometric bite at approximately 10% maximum. With jaw muscles relaxed, a servo-controlled stretcher evoked a stretch reflex in masseter which was conditioned by TMS (1.3x AMT) at 14 different conditioning-testing intervals. There were 20 trials at each interval, in random order. TMS evoked no MEP in resting masseter, but often produced a small MEP in digastric. RESULTS: Mean (+/-SE) masseter CSP was 67+/-3ms. The masseter stretch reflex was facilitated when stretch preceded TMS by 8 and 10ms, which we attribute to spatial summation of corticobulbar and Ia-afferent excitatory inputs to masseter. Masseter stretch reflex amplitude was reduced when TMS was given up to 75ms before stretch, and for up to 2ms afterwards. CONCLUSIONS: We conclude that descending corticobulbar activity evoked by TMS acts bilaterally on brainstem interneurons that either inhibit masseter motoneurons or increase pre-synaptic inhibition of Ia-afferent terminals for up to 75ms after TMS. The reduction of masseter motoneuron pool excitability following TMS has a similar time-course to the CSP. SIGNIFICANCE: In contrast to the situation for spinal and facial (CN VII) muscles, the masseter CSP appears to have no component that can be attributed exclusively to cortical mechanisms. Abnormalities in the masseter cortical silent period observed in neurological conditions may be due to pathophysiological changes at cortical and/or sub-cortical levels.     

Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex

OBJECTIVE: To study whether trains of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) over premotor, prefrontal, or parietal cortex can produce changes in excitability of motor cortex that outlast the application of the train. BACKGROUND: Prolonged 1 Hz rTMS over the motor cortex can suppress the amplitude of motor-evoked potentials (MEP) for several minutes after the end of the train. Because TMS can produce effects not only at the site of stimulation but also at distant sites to which it projects, the authors asked whether prolonged stimulation of sites distant but connected to motor cortex can also lead to lasting changes in MEP. METHODS: Eight subjects received 1500 magnetic stimuli given at 1 Hz over the left lateral frontal cortex, the left lateral premotor cortex, the hand area of the left motor cortex, and the left anterior parietal cortex on four separate days. Stimulus intensity was set at 90% active motor threshold. Corticospinal excitability was probed by measuring the amplitude of MEP evoked in the right first dorsal interosseous muscle by single suprathreshold stimuli over the left motor hand area before, during, and after the conditioning trains. RESULTS: rTMS over the left premotor cortex suppressed the amplitude of MEP in the right first dorsal interosseous muscle. The effect was maximized (approximately 50% suppression) after 900 pulses and outlasted the full train of 1500 stimuli for at least 15 minutes. Conditioning rTMS over the other sites did not modify the size of MEP. A control experiment showed that left premotor cortex conditioning had no effect on MEP evoked in the left first dorsal interosseous muscle. CONCLUSIONS: Subthreshold 1 Hz rTMS of the left premotor cortex induces a short-lasting inhibition of corticospinal excitability in the hand area of the ipsilateral motor cortex. This may provide a model for studying the functional interaction between premotor and motor cortex in healthy subjects and patients with movement disorders.     

The comparable size and overlapping nature of upper limb distal and proximal muscle representations in the human motor cortex

The purpose of this study was to determine the relative size and location of proximal and distal upper limb muscle representations in the human motor cortex. Motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation were recorded in the proximal muscle anterior deltoid (AD) and in the distal muscles extensor carpi radialis (ECR) and first dorsal interosseus (1DI). The coil was moved in steps of 1 cm along a grid drawn on a tight-fitting polyester cap placed on the subject's head. At each location, four stimuli were delivered at 1.2 times the active motor threshold (AMT), and MEPs averaged in real-time. The peak-to-peak amplitude of each muscle's mean MEP was measured at each stimulation site. The area of a muscle's representation was measured by a pixel-counting algorithm. The optimal point of each muscle's areal representation, which corresponds to the locus near which the largest MEPs are obtained, was determined by fitting a 3D Lorentzian function to the data points. The optimal point of distal muscles tended to be situated more laterally along the motor strip than that of proximal muscles. However, there was no statistically significant difference between the size of the areal representations and they overlapped considerably. Additionally, in another five subjects, using a small 45-mm coil placed in a hyper-focal orientation, maps were obtained at a stimulus intensity of 1.1-1.15 times the AMT of the muscle with the lowest threshold, usually the 1DI. Even in this very stringent condition, the mapped representations of the AD, ECR and 1DI overlapped, notwithstanding that sharp demarcations between borders were also apparent. These observations demonstrate that stimulus spread alone does not explain the overlap of muscle representations. These results show that commonly used proximal and distal upper-limb muscles, taken individually, are controlled by motor cortical territories of approximately equal size that significantly overlap despite differences in the location of their optimal points.     

Central fatigue and motor cortical excitability during repeated shortening and lengthening actions

A decline in voluntary muscle activation and adaptations in motor cortical excitability contribute to the progressive decline in voluntary force during sustained isometric contractions. However, the neuronal control of muscle activation differs between isometric and dynamic contractions. This study was designed to investigate voluntary activation, motor cortex excitability, and intracortical inhibition during fatiguing concentric and eccentric actions. Eight subjects performed 143 torque motor-controlled, repeated shortening and lengthening actions of the elbow flexor muscles. Transcranial magnetic stimulation (TMS) was applied three times every 20 cycles. Magnetic evoked motor potentials (MEP), duration of the silent period (SP), and the torque increase due to TMS were analyzed. TMS resulted in a small torque increase in unfatigued actions. With repeated actions, voluntary torque dropped rapidly and the amplitude of the TMS-induced twitches increased, especially during repeated lengthening actions. MEP area of biceps brachii and brachioradialis muscles increased during repeated actions to a similar extent during lengthening and shortening fatigue. The duration of biceps and brachioradialis SP did not change with fatigue. Thus, voluntary activation became suboptimal during fatiguing dynamic actions and motor cortex excitability increased without any changes in intracortical inhibition. The apparent dissociation of voluntary activation and motor cortex excitability suggests that the central fatigue observed, especially during lengthening actions, did not result from changes in motor cortex excitability.     

Decreased input to the motor cortex increases motor cortical excitability.

OBJECTIVE: To investigate whether a short-duration reduction of input to the motor cortex affects excitability in the hand region of the motor cortex. METHODS: Subjects (n=10) received sets of transcranial magnetic stimulation of the motor cortex (TMS) and peripheral ulnar nerve stimulation. Stimuli were delivered before and after 20 min of inactivity of the test hand. The evoked compound muscle action potentials were recorded in two relaxed intrinsic hand muscles using surface EMG. RESULTS: Motor evoked potential size (MEP; expressed relative to the maximal M-wave) increased by approximately 30-40 in both hand muscles (P=0.012) following inactivity. The enlarged MEP was not associated with changes in F-wave size, a marker of motoneurone excitability, or changes in intracortical inhibition and facilitation measured with paired-pulse TMS. CONCLUSIONS: MEP growth most likely reflects an increase in motor cortical excitability. The increased excitability appears to be more associated with reduced voluntary drive to and from the motor cortex rather than reduced afferent input from the periphery. SIGNIFICANCE: These results have important implications for any investigation of motor cortical excitability in relaxed subjects. The outcome of an experimental intervention is the net result of the intervention itself and alterations in cortical excitability produced by the subjects' inactivity.     

Effect of therapy on motor cortical excitability in Parkinson's disease

OBJECTIVE: To assess the impact of the disease stage and therapy on motor cortical excitability in Parkinson's disease (PD). METHODS: Twenty newly diagnosed and medication-free, early stage patients, 20 late stage patients under antiparkinsonian therapy and 20 normal healthy controls were included. Motor threshold (MT), amplitudes of motor evoked potential (MEP), motor evoked potential amplitude/compound muscle action potential amplitude (MEP/CMAP) ratio, central motor conduction time (CMCT) and cortical silent period (CSP) were measured by stimulation of the motor cortex using a 13.5 cm circular coil and recordings from abductor digiti minimi muscle. Following the first study protocol, early stage patients were given therapy and the same protocol was repeated three months later. RESULTS: Motor threshold was lower; and the MEP/CMAP ratio was higher in early and late stage patients than normals. In early stage patients after proper therapy, the MTs became higher than before therapy, but still remained lower than normals. In late stage patients, the CMCTs were shorter than the early stage patients before therapy and normals, but there was no difference between the early stage patients and normals. In early stage patients after therapy, the CMCT became longer than before therapy and this difference was significant in both late stage patients and normals. Although more prominent in late stage patients, the CSP duration in both PD groups was found shorter than normals. In early stage patients, after therapy, the CSP durations became significantly longer compared with before therapy. CONCLUSION: These findings suggest that the motor cortical excitability increases in PD because of the impairment of the corticomotoneuronal inhibitory system.     

Excitability Profile of Motor Evoked Potentials and Silent Periods

The aim of this study was to confirm the excitability profile of human cortical circuits on the motor evoked potential (MEP) and the silent period (SP) after paired transcranial magnetic stimulation (TMS) with variable interstimulus intervals (ISI), and to compare the time courses of MEP and SP after paired TMS at variable ISIs. MEPs were elicited at the hypothenar muscles at rest, and during tonic muscle contraction by applying paired TMS to the motor cortex. The authors measured the MEP amplitude during rest and the duration of SP during tonic muscle contraction at various ISIs. The response to paired stimuli was inhibited by an ISI of 1–5 ms and facilitated by an ISI of 10–20 ms. The SP at an ISI of 1–5 ms was shorter than that at the single suprathreshold stimulus, but the SP at an ISI of 15–25 ms was longer than this. A significant correlation was observed between the MEP amplitude and the duration of SP at ISIs of 1–20 ms and for a CS of 80% of threshold. These results may provide useful data for the study of the function of cortical excitability in disease states and suggest that the neural circuits underlying MEP and SP differ partly.     

Repetitive transcranial magnetic stimulation reveals abnormal plastic response to premotor cortex stimulation in schizophrenia.

BACKGROUND: Schizophrenia may be characterized by abnormal plastic modulation in cortical neuronal circuits. Activation of premotor cortex using repetitive transcranial magnetic stimulation (rTMS) produces suppression of cortical excitability in primary motor cortex. We hypothesized that premotor rTMS would cause less suppression of motor cortical excitability in patients with schizophrenia than in control subjects. METHODS: Twelve patients diagnosed with schizophrenia and twelve healthy control subjects underwent subthreshold rTMS to the premotor area in a 15-min conditioning train. Measurements of primary motor cortical excitability (motor evoked potential; MEP), the resting motor threshold (RMT), and cortical inhibition (CI) were taken before and after the rTMS. RESULTS: There was no difference in RMT between groups at baseline, although the patient group had less CI than the control group at baseline. Following rTMS, the change in both MEP size and RMT between groups was significant. After rTMS, MEP size was suppressed in the control group and increased in the patient group, whereas RMT increased in the normal control group and decreased in the patient group. CONCLUSIONS: Patients with schizophrenia demonstrate abnormal brain responses to rTMS applied to the premotor cortex that appear to relate to reduced motor cortical inhibition.     

Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior.

OBJECTIVE: To explore effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) on motor excitability and basic motor behavior in humans.Design and METHODS: Seven normal volunteers underwent 1 Hz rTMS of the hand representation of the right M1 for 15 min at an intensity of 115% of the individual resting motor threshold. The effects of rTMS on motor excitability were assessed by monitoring changes in individual resting motor threshold and input-output curves of motor evoked potentials (MEPs) in the flexor pollicis brevis, first dorsal interosseus, abductor digiti minimi and biceps brachii muscles. Changes in basic motor behavior were studied by measuring maximal and mean peak force and peak accelerations of thumb flexions and abductions of the fifth finger before and after rTMS. RESULTS: rTMS produced a significant increase in resting motor threshold and a significant suppression of MEP input-output curves that persisted for 30 min. The suppressing effect was restricted to the hand motor representation which was the prime target of the stimulation procedure, and there were no significant effects on the biceps representation. Peak force and peak acceleration were not affected while the motor representations of muscles involved in the behavioral measurements were significantly suppressed by rTMS. CONCLUSIONS: Low-frequency rTMS of M1 transiently depresses motor excitability but this does not affect basic motor behavior. This is relevant for the therapeutic use of low-frequency rTMS in disorders with abnormal cortical excitability.     

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia

To find out whether botulinum toxin alters the excitability of cortical motor areas, we studied intracortical inhibition with transcranial magnetic stimulation in patients with upper limb dystonia before, 1 month after, and 3 months after the injection of botulinum toxin type A in the affected muscles. Eleven normal subjects and 12 patients with dystonia involving the upper limbs (7 with generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were studied. Patients were assessed clinically with the Dystonia Movement Scale. Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators connected through a Bistim module to a figure-of-eight coil placed over the motor area of the forearm muscles. Paired stimulation was given at rest. A subthreshold (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before the suprathreshold (120% of motor threshold) test stimulus. Electromyographic signals were recorded over the flexor or extensor muscles of the forearm on the affected side. We measured the amplitude of the test motor evoked potential (expressed as a percentage of the unconditioned motor evoked potential). All results were compared using ANOVA. In all patients, a botulinum toxin type A injection (50-100 mouse units) reduced dystonic movements in the arm. In normal subjects, electromyographic recordings showed significant inhibition of the test response. Before botulinum toxin injection, patients had less test response inhibition than normal subjects. One month after injection, patients had test response inhibition similar to that of normal subjects. At 3 months after injection, they again had less inhibition than normal subjects or patients at 1 month after injection. In conclusion, our data suggest that botulinum toxin can transiently alter the excitability of the cortical motor areas by reorganizing the inhibitory and excitatory intracortical circuits. The cortical changes probably originate through peripheral mechanisms.     

Post-stroke reorganization of hand motor area: a 1-year prospective follow-up with focal transcranial magnetic stimulation.

OBJECTIVE: Focal transcranial magnetic stimulation was used to test prospectively corticospinal excitability changes and reorganization of first dorsal interosseous (FDI) motor cortical representation in 31 patients who experienced a first ischemic stroke in the middle cerebral artery territory. All had severe hand palsy at onset. METHODS: Patients were assessed clinically with the Medical Research Council, Rankin, the National Institutes of Health stroke scales and Barthel Index at days 1, 8, 30, 90, 180 and 360 after stroke. The following parameters of FDI motor evoked potential (MEPS) to focal transcranial magnetic stimulation were measured at the same delays: motor threshold, MEP amplitude, excitable cortical area, hot spot and center of gravity of FDI motor maps on affected and unaffected hemispheres. Correlations were sought between clinical and electrophysiological parameters. RESULTS: In patients whose affected motor cortex remained excitable at day 1, motor thresholds were not significantly different between sides and were similar to those of controls. Persistence of MEP on the affected side at day 1 was a strong predictor of good recovery. If present at day 1, MEPs recorded in affected FDI were significantly smaller than of the opposite side or in normals and progressively recovered up to day 360. In these patients, area of excitable cortex remained stable throughout the entire study. At day 1, amplitudes of MEPs obtained in unaffected FDI were significantly larger than later. Between days 1 and 360, we observed a significant displacement of center of gravity of motor maps towards more frontal regions on the affected side while no change was noted on the unaffected side. CONCLUSIONS: Our data confirm the early prognosis value of transcranial magnetic stimulation in stroke. They indicate that the brain insult induces a transient hyperexcitability of the unaffected motor cortex. The evolution of FDI motor maps along the course of recovery mostly reflect corticospinal excitability changes but might also reveal some degree of brain plasticity. Most modifications observed occurred within 3 months of stroke onset.     

Changes in motor cortex excitability during ipsilateral hand muscle activation in humans.

OBJECTIVES: To test whether unilateral hand muscle activation involves changes in ipsilateral primary motor cortex (M1) excitability. METHODS: Single- and paired-pulse transcranial magnetic stimulation (TMS) of the right hemisphere was used to evoke motor evoked potentials (MEPs) from the resting left abductor pollicis brevis (APB) in 9 normal volunteers. We monitored changes in motor threshold (MT), MEP recruitment, intracortical inhibition (ICI) and intracortical facilitation (ICF) while the ipsilateral right APB was either at rest or voluntarily activated. Spinal motoneuron excitability was assessed using F-wave recording procedures. RESULTS: Voluntary muscle activation of the ipsilateral APB significantly facilitated the MEPs and F-waves recorded from the contralateral APB. Facilitation was observed with muscle activation >50% of the maximum voluntary force and with stimulus intensities >20% above the individual resting motor threshold. Intracortical inhibition significantly decreased in the ipsilateral M , while there was no significant change in intracortical facilitation during this maneuver. CONCLUSIONS: Unilateral hand muscle activation changes the excitability of homotopic hand muscle representations in both the ipsilateral M1 and the contralateral spinal cord. While the large proportion of MEP facilitation most likely occurred at a spinal level, involvement of the ipsilateral hemisphere may have contributed to the enlargement of magnetic responses.     

Corticospinal excitability during motor imagery of a simple tonic finger movement in patients with writer's cramp.

Motor imagery (MI) is the mental rehearsal of a motor act without overt movement. Using transcranial magnetic stimulation (TMS), we tested the effect of MI on corticospinal excitability in patients with writer's cramp. In 10 patients with writer's cramp and 10 healthy controls, we applied focal TMS over each primary motor area and recorded motor evoked potentials (MEPs) from contralateral hand and arm muscles while participants imagined a tonic abduction of the index finger contralateral to the stimulated hemisphere. In healthy controls and patients, the MEP amplitude in the relaxed first dorsal interosseus muscle (FDI) showed a muscle-specific increase during MI; however, the increase was less pronounced in patients than in healthy controls. In addition, in patients but not in controls, the MEP amplitude also increased in hand and forearm muscles not involved in the imagined movement. This abnormal spread of facilitation was observed in the affected and unaffected upper limb. MI of simple hand movements is less efficient and less focussed in patients with writer's cramp than it is in normal subjects.     

Mirtazapine increases cortical excitability in healthy controls and epilepsy patients with major depression

BACKGROUND: Epilepsy is often complicated by depression requiring antidepressant treatment. Such treatment might be proconvulsive. OBJECTIVE: To examine the effects of the noradrenergic and specific serotonergic antidepressant mirtazapine on motor cortex excitability in epilepsy patients with depression and in healthy controls, using transcranial magnetic stimulation (TMS). METHODS: Seven clinically depressed epilepsy patients treated with anticonvulsant drugs and six healthy volunteers were studied. Before intake of mirtazapine and 24 hours afterwards (and also three weeks afterwards in the patients), the active and resting motor threshold (AMT, RMT), the size of the motor evoked potential (MEP), the cortical silent period (SP), and intracortical inhibition/facilitation and intracortical facilitatory I wave interactions were determined using single and paired pulse TMS. RESULTS: At baseline, AMT and RMT were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP area greater in patients (p = 0.041). In patients but not in healthy subjects AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had no significant effect on the MEP size, duration of the SP, or the ratio of SP duration to MEP size in patients. The duration of the SP was longer (p = 0.037) but the ratio of SP duration to MEP size remained similar in healthy subjects after mirtazapine. There were no significant differences in paired pulse measures between the two groups either at baseline or after mirtazapine. CONCLUSIONS: Mirtazapine increased neuronal excitability of pyramidal tract axons in an activated state in both healthy controls and epilepsy patients with major depression.     

Facilitatory effect of thinking about movement on magnetic motor-evoked potentials

To investigate the facilitatory effect of thinking about movement on motor evoked potential (MEP) amplitude, we recorded MEPs in two test muscles during rest, with the subject thinking about contracting the test muscle but without subsequent contraction, and during 10% maximum voluntary contraction. Stimuli were delivered at 10% above resting motor threshold and at 90–100% stimulator output. H-reflexes, recorded in flexor carpi radialis, were obtained during rest and think conditions. MEP threshold was lower during the think condition (P=0.004). At both stimulus intensities, median MEP amplitudes and areas were significantly (P<0.001) larger during the think paradigm compared with rest. This effect was greater at the lower stimulus intensity. There was no significant difference in latency (P=0.15). In 4/8 subjects, H-reflex amplitudes were mildly facilitated (P<0.05) during the think condition. We conclude that thinking about movement without detectable EMG activity has a facilitatory effect on magnetic MEPs. The absence of a MEP latency shift between rest and think conditions and absence of a consistent increase in H-reflex amplitude suggests this effect occurs largely at the cortical level. In some subjects, however, an increase in spinal motoneuron excitability may also contribute.     

Magnetic brain stimulation: the silent period after the motor evoked potential.

In 25 normal subjects, we studied the EMG silent period following the magnetic motor evoked potential (MEP) when the target muscle was tonically contracted (post-EMP silent period [PMSP]). In the first dorsal interosseous muscle (FDI), PMSP duration increased in linear proportion to stimulus intensity, but not to the size of the preceding MEP. The PMSP was longer in hand and forearm muscles than in upper arm muscles. In the FDI, PMSP was longer than the peripheral silent period (PSP) even when multiple peripheral stimuli were used to get M responses whose twitch force was equivalent to that of MEPs. Weak magnetic stimuli evoked silent periods preceded by no MEP in several subjects. Spinal alpha-motoneurons (alpha-MNs) were partially inhibited during the first PMSP portion, but later this effect recovered. MEPs due to weak electrical stimuli to motor cortex were only slightly inhibited during the late PMSP. Segmental inhibitory loops evoked by the muscle twitch and inhibitory projections descending to alpha-MNs from the cortex predominantly underlie earlier PMSP portions, but recurrent intracortical inhibition may also contribute. Later portions are predominantly due to other stimulus-related cerebral inhibitory or suppressing phenomena.     

Excitability profile of motor evoked potentials and silent periods

The aim of this study was to confirm the excitability profile of human cortical circuits on the motor evoked potential (MEP) and the silent period (SP) after paired transcranial magnetic stimulation (TMS) with variable interstimulus intervals (ISI), and to compare the time courses of MEP and SP after paired TMS at variable ISIs. MEPs were elicited at the hypothenar muscles at rest, and during tonic muscle contraction by applying paired TMS to the motor cortex. The authors measured the MEP amplitude during rest and the duration of SP during tonic muscle contraction at various ISIs. The response to paired stimuli was inhibited by an ISI of 15 ms and facilitated by an ISI of 1020 ms. The SP at an ISI of 15 ms was shorter than that at the single suprathreshold stimulus, but the SP at an ISI of 1525 ms was longer than this. A significant correlation was observed between the MEP amplitude and the duration of SP at ISIs of 120 ms and for a CS of 80% of threshold. These results may provide useful data for the study of the function of cortical excitability in disease states and suggest that the neural circuits underlying MEP and SP differ partly.     

Dual modulating effects of amphetamine on neuronal excitability and stimulation-induced plasticity in human motor cortex.

OBJECTIVES: The objective of the present study is to test the modulating effects of dextro-amphetamine (d-AMP) on excitability and stimulation-induced plasticity in human motor cortex. METHODS: Transcranial magnetic stimulation (TMS) was used to measure motor threshold, motor evoked potential (MEP) size and paired-pulse intracortical facilitation (ICF) in the biceps muscle of 7 healthy subjects before and after two different experimental manipulations: temporary forearm ischemic nerve block (INB) alone, or INB plus 0.1 Hz repetitive TMS (INB+rTMS) of the motor cortex contralateral to INB. Both manipulations were run after treatment with 10mg of d-AMP or placebo (PBO). RESULTS: In the PBO experiments, INB alone had no significant effect on MEP size or ICF, while INB+rTMS produced long-lasting (>60 min) increases. Compared with PBO, d-AMP led to a short-lasting ( approximately 10 min) increase in MEP size in the INB alone experiment, but suppressed the long-lasting increases of MEP size and ICF in the INB+rTMS experiment. CONCLUSIONS: The present findings suggest that d-AMP increases neuronal excitability but suppresses long-lasting stimulation-induced plasticity in human motor cortex. These dual effects may be relevant when using d-AMP to modulate human cortex function.