Zonisamide decreases cortical excitability in patients with idiopathic generalized epilepsy.

ObjectiveTo evaluate changes in cortical excitability after long-term zonisamide (ZNS) administration.MethodsFifteen drug-naïve idiopathic generalized epilepsy (IGE) patients (8 male, mean age 24.9 years) were enrolled. The transcranial magnetic stimulation (TMS) parameters obtained using two Magstim 200 stimulators were resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, cortical silent period (CSP), intracortical inhibition (ICI), and intracortical facilitation (ICF). TMS parameters were compared before and after ZNS administration.ResultsAll patients were administered ZNS monotherapy (200 mg/day) for 8 weeks. No patient reported seizures during the study period. After ZNS treatment MEP amplitudes were significantly reduced in right (−34.2%) and left hemispheres (−37.0%) (Wilcoxon’s signed rank test after Bonferroni’s correction for multiple comparisons, P < 0.05). Mean RMT, CSP, and ICI/ICF were not changed by ZNS (P > 0.05).ConclusionsThese findings suggest that ZNS decreases cortical excitability in patients with IGE and a MEP amplitude is a useful TMS parameter for evaluating changes in cortical excitability induced by ZNS.SignificanceThe findings in this study are helpful to understand how ZNS affects the excitability of the motor cortex in patients with IGE.     

Serum levels of carbamazepine and cortical excitability by magnetic brain stimulation

Abstract. We investigated the correlation between serum levels of carbamazepine (CBZ) and motor excitability studied by different parameters of transcranial magnetic stimulation (TMS) in patients at the beginning of antiepileptic treatment. A total of 10 patients with complex partial seizures following stroke were treated with loading doses of CBZ. Motor evoked potential (MEP) was recorded from the thenar eminence (TE) muscles of the unaffected arm. In all patients, we studied rest and active motor threshold (rMT, aMT), MEP amplitude and cortical silent period (CSP). In three patients, intracortical inhibition (ICI) and intracortical facilitation (ICF) were measured using paired TMS at short interstimulus intervals (1–25 ms). The recording sessions were performed before treatment and after 7, 15 and 60 days (SD=16 days). Serum level of CBZ were monitored at each recording session. We observed a progressive increase in rMT and aMT until the serum levels of CBZ reached a steady state condition. No significant changes were observed in MEP amplitude, CSP, ICI and ICF. This study documents the increase of both motor threshold and drug serum levels in patients treated with loading doses of CBZ, suggesting a relationship between drug metabolism and the effect on motor cortical excitability.     

Intravenous clomipramine decreases excitability of human motor cortex. A study with paired magnetic stimulation

Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). In these studies, paired magnetic stimulation has been used in normal subjects and on patients who were taking different antiepileptic drugs. The aim of our study was to investigate motor area excitability on depressed patients after intravenous administration of a single dose of clomipramine, a tricyclic antidepressant. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation (TMS) before and after 4, 8 and 24 h from intravenous administration of 25 mg of clomipramine. Cortical excitability was measured using different TMS parameters: motor threshold (MT), motor evoked potential (MEP) amplitude, duration of cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF). Spinal excitability and peripheral nerve conduction was measured by F response and M wave. A temporary but significant increase of motor threshold and intracortical inhibition and a decrease of intracortical facilitation were observed 4 h following drug administration. MEP amplitude, cortical silent period, F response and M wave were not significantly affected by drug injection. Our findings suggest that a single intravenous dose of clomipramine can exert a significant but transitory suppression of motor cortex excitability in depressed patients. TMS represents a useful research tool in assessing the effects of motor cortical excitability of neuropsychiatric drugs used in psychiatric disease.     

Inter-hemispheric asymmetry of motor corticospinal excitability in major depression studied by transcranial magnetic stimulation

BACKGROUND: Imaging and electroencephalographic studies have reported inter-hemispheric asymmetries in frontal cortical regions associated with depression. This study aimed at comparing motor corticospinal excitability assessed by methods of transcranial magnetic stimulation (TMS) between the right and left hemispheres in patients with major depression and healthy controls. METHOD: Patients with major depression (n=35) and healthy controls (n=35) underwent a bilateral study of various motor corticospinal excitability parameters, including rest motor threshold (RMT), corticospinal silent period (CSP) duration and intra-cortical inhibition (ICI) and facilitation (ICF). Indexes of asymmetry were calculated, and the relationships between excitability parameters and clinical scores of depression were statistically analyzed. RESULTS: Depressed patients showed a reduced excitability of both excitatory (RMT, ICF) and inhibitory (CSP, ICI) processes in the left hemisphere, compared to the right hemisphere and to healthy controls. CONCLUSION: The present results confirmed the existence of inter-hemispheric asymmetries in frontal cortex activities of depressed patients in favor of a left-sided reduced excitability. This neurophysiological approach may help to guide repetitive TMS procedures in the treatment of depressive disorders.     

Different mechanisms contribute to motor cortex hyperexcitability in amyotrophic lateral sclerosis.

OBJECTIVES: Different physiological approaches demonstrated motor system hyperexcitability in amyotrophic lateral sclerosis (ALS), probably reflecting excitotoxic mechanisms. Transcranial magnetic stimulation (TMS) showed that both increased excitability of corticomotoneurons and reduced intracortical inhibition (ICI) contribute to motor cortex hyperexcitability, but the importance of these factors in inducing this cortical dysfunction is unknown. The aim of the study was to establish how different mechanisms interact to promote motor system hyperexcitability in ALS in relation to clinical features. METHODS: The resting motor threshold (RMT), the motor evoked potential (MEP) recruitment curve and the cortical silent period (CSP) to single-pulse TMS were evaluated in 35 patients with ALS. Early ICI and intracortical facilitation (ICF) and late ICI were evaluated by paired TMS. RESULTS: The main abnormal TMS findings were: (a) a steeper MEP recruitment curve associated with a lowering of the RMT; (b) reduced or even absent early and late ICI; (c) reduced CSP lengthening with increasing TMS intensity. ICF was not affected. RMT increased and the MEP recruitment curve became less steep with longer disease duration, but they did not correlate with the motor deficit, the type of motoneuron affection and the decrease of ICI. Impairment of early and late ICI were significantly correlated to each other, to disease severity and to clinical evidence of upper motor neuron involvement. CONCLUSIONS: Different and partially independent mechanisms contribute to motor cortex hyperexcitability in ALS. The increased gain in MEP recruitment with a lowering of the RMT appears to be a primary event reflecting an increase in the strength of corticospinal projections, probably related to changes in the ion-channel permeability of the neuronal membrane. On the other hand, inhibitory functions linked to multiple neurotransmitter systems decline with disease progression. Both depletion of specific subpopulations of intracortical GABAergic neurons and mechanisms involved in motor cortex reorganization following progressive neuronal loss have been considered to account for the impaired inhibition. The clarification of the importance of these factors in the pathogenesis of ALS may have diagnostic and therapeutic implications.     

Modification of cortical excitability induced by gabapentin: a study by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) was employed before and after a single dose of gabapentin to evaluate how this drug affects the activity of excitatory and inhibitory circuits within the motor cortex. Eleven healthy volunteers were studied. For the evaluation of cortical excitability, the following parameters were taken into account: resting and active motor threshold (RMT, AMT); cortical silent period (CSP); and intracortical inhibition (ICI) and facilitation (ICF). Peripheral silent period (PSP) was also detected. All parameters were measured before and 3 and 24 hours after 800 mg gabapentin was administered in a single oral dose. Gabapentin deepened the ICI and suppressed the ICF at 3 h but not at 5 h after dosing. We conclude that, in the normal human brain, gabapentin may act on intracortical excitability by shifting the balance towards less excitation and more inhibition. Received: 30 March 2001 / Accepted in revised form: 17 May 2001     

Effect of levetiracetam on cortical excitability: a transcranial magnetic stimulation study

Background and purpose:  We studied the effect of levetiracetam (LEV), an anticonvulsant with a novel mechanism of action, on cortical excitability, measured using transcranial magnetic stimulation (TMS). For this purpose, 38 healthy volunteers were assessed in two TMS sessions, before and after an oral dose of 3000 mg LEV.
Methods:  Resting motor threshold (RMT), intracortical facilitation (ICF) and intracortical inhibition (ICI), cortical silent period (CSP) threshold and duration and motor-evoked potential (MEP) amplitude were calculated.
Results:  After treatment with LEV, RMT was increased (mean ± SD: 63 ± 14% of the maximum stimulator output) compared with baseline (58 ± 11%). CSP threshold was decreased after LEV (54 ± 10%; baseline, 57 ± 11%). CSP duration was increased after LEV (116 ± 37 ms; baseline: 102 ± 33 ms). LEV did not affect ICF or ICI or mean MEP amplitude significantly.
Conclusions:  Our results indicate that LEV modulates some aspects of cortical excitability. Whereas the increase in the RMT most probably reflects the effect of LEV on ion channel activity, effects on the CSP might represent a modulation of GABA receptors at cortical and spinal level.     

Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue.

How the human brain controls activation of the ipsilateral part of midline muscles is unknown. We studied corticospinal and corticocortical network excitability of both ipsilateral and contralateral motor representations of the tongue to determine whether they are under analogous or disparate inhibitory and facilitatory corticocortical control. Motor evoked potentials (MEPs) to unilateral focal transcranial magnetic stimulation (TMS) of the tongue primary motor cortex were recorded simultaneously from the ipsilateral and contralateral lingual muscles. Single-pulse TMS was used to assess motor threshold (MT) and MEP recruitment. Paired-pulse TMS was used to study intracortical inhibition (ICI) and intracortical facilitation (ICF) at various interstimulus intervals (ISIs) between the conditioning stimulus (CS) and the test stimulus (TS), and at different CS and TS intensities, respectively. Focal TMS invariably produced MEPs in both ipsilateral and contralateral lingual muscles. MT was lower and MEP recruitment was steeper when recorded from the contralateral muscle group. ICI and ICF were identical in the ipsilateral and contralateral representations, with inhibition occurring at short ISIs (2 and 3 ms) and facilitation occurring at longer ISIs (10 and 15 ms). Moreover, changing one stimulus parameter regularly produced analogous changes in MEP size bilaterally, revealing strong linear correlations between ipsilateral and contralateral ICI and ICF (P < 0.0001). These findings indicate that the ipsilateral and contralateral representations of the tongue are under analogous inhibitory and facilitatory control, possibly by a common intracortical network.     

Motor cortical excitability in patients with poststroke epilepsy

PURPOSE: To gain insight into the mechanisms underlying poststroke epilepsy (PSE), we evaluated motor cortical function in chronic stroke patients with (N = 18) and without (N = 18) PSE. METHODS: We measured resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, cortical silent period (CSP), intracortical inhibition (ICI), influenced by GABAergic neurotransmission, and intracortical facilitation (ICF), influenced by glutamatergic activity, to transcranial magnetic stimulation. RESULTS: We found (1) larger MEP amplitudes and ICF, in the affected than unaffected hemispheres of patients in the PSE group but not in patients without epilepsy, and (2) comparably higher RMT and longer CSP in the absence of differences in ICI, H-reflexes or F-waves in the affected and unaffected hemispheres of both PSE and non-PSE patients. CONCLUSIONS: Enhanced cortical excitability in the affected hemisphere, possibly related to increased glutamatergic activity, could be one of the mechanisms contributing to the development of poststroke epilepsy.     

Selective and nonselective benzodiazepine agonists have different effects on motor cortex excitability

Transcranial magnetic stimulation (TMS) is a useful method to study pharmacological effects on motor cortex excitability. Zolpidem is a selective agonist of the benzodiazepine receptor subtype BZ1 and has a distinct pharmacological profile compared to diazepam. To study the different effects of these two drugs on the cortical inhibitory system, TMS was performed before and after administration of a single oral dose of zolpidem (10 mg) and diazepam (5 mg) in six healthy volunteers. TMS tests included the determination of resting and active motor threshold (MT) and measurements of the amplitudes of motor evoked potentials, intracortical facilitation (ICF), short-latency intracortical inhibition (SICI), and long-latency intracortical inhibition (LICI), and determination of the cortical silent period (CSP). Both drugs were without effect on the active or resting MT and decreased the ICF. Prolongation of the CSP and enhancement of LICI only in the presence of zolpidem point to a specific BZ1-related mechanism underlying the long-lasting component of cortical inhibition. This selective modulation of the CSP and the LICI points to a specific role of BZ1 receptors in the control of inhibitory neuronal loops within the primary motor cortex.     

Does the recruitment of excitation and inhibition in the motor cortex differ?

The level of excitability within the motor cortex can be described as a balance between excitation and inhibition, but it is unknown how well both processes correlate. To address this question, the authors measured motor cortical excitability and inhibition in healthy human subjects, comparing the recruitment of motor evoked potentials (MEPs) and the duration of the cortical silent period (CSP) after transcranial magnetic stimulation (TMS). Single-pulse "focal" TMS was applied at intensities varying between 90% and 200% of motor thresholds to the right motor cortex of 15 healthy volunteers. The peak-to peak size of MEP responses and the duration of the CSP were measured in small hand muscles. Stimulus-response (S-R) curves were constructed by plotting the MEP size and CSP duration against stimulus intensities. The absolute duration of CSP and the size MEPs correlated significantly and to a similar extent with stimulus intensity (r = 0.60 and 0.53, respectively). The slope of the MEP-S-R was steeper compared with CSP-S-R, particularly at low stimulation intensities. CSP duration saturated earlier and CSP-S-Rs were shifted upwards at a given stimulus intensity compared with MEP-S-Rs. The findings suggest that recruitment of inhibition and excitation within the sensorimotor cortex correlate. However, inhibitory effects are recruited at lower intensities and saturate earlier than excitation.     

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.     

Depressed intracortical inhibition after long trains of subthreshold repetitive magnetic stimuli at low frequency

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability. These effects outlast the rTMS train, and range from inhibition to facilitation according to the variables used for rTMS. Several studies have demonstrated short and long-term effects on motor evoked potential (MEP) size, whereas the effects on intracortical inhibition (ICI) and facilitation (ICF) are still unclear. We investigated short- (1-15 min), intermediate- (16-30 min), and long-term (6 h) effects on intracortical excitability. METHODS: Fourteen healthy subjects were stimulated with rTMS trains of 900 pulses (1 Hz, 90% resting motor threshold (rMTh)), delivered over the primary motor cortex and the occipital area. MTh, MEP size, silent period, intracortical inhibition at short (ICI) and long inter-stimulus intervals, and ICF were tested before and after rTMS. RESULTS: ICI was reduced 16-30 min after 1 Hz rTMS trains over the primary motor area, whereas the other response variables remained unchanged. The ICI reduction at 16-30 min was reproducible on different days in the same subjects; it was absent at 6 h and after stimulation of the occipital area. CONCLUSIONS: Subthreshold 1 Hz rTMS decreases ICI by reducing the excitability of intracortical inhibitory interneurones or by altering the electrical properties of the facilitatory chain of neurons responsible for the I waves.     

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.     

The effect of modafinil on cortical excitability in patients with narcolepsy: A randomized,placebo-controlled,crossover study

ObjectiveTo investigate the effect of modafinil on cortical excitability in patients with narcolepsy using transcranial magnetic stimulation (TMS).MethodsNineteen drug-naïve narcolepsy patients with cataplexy (10 males, 9 females, and mean age 28.5 years) and 25 age- and sex-matched healthy controls were recruited. In this double-blind, randomized, crossover study, patients and controls received a single dose of 400 mg modafinil or placebo. Modafinil and placebo administrations were separated by a 2-week washout period. TMS parameters, such as resting motor thresholds (RMT), motor-evoked potential (MEP) amplitudes, cortical silent periods (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), were measured before and 3 h after administering modafinil or placebo. The differences of TMS parameters were statistically tested between patients and controls and between before and after modafinil or placebo administration.ResultsNarcolepsy patients had significantly increased CSP durations compared to controls (independent t-test, P < 0.05), indicating decreased excitability of cortical networks in human narcolepsy. In patients after modafinil administration, MEP amplitudes, SICI, and ICF increased, and CSP duration shortened significantly, meaning enhanced motor excitability, whereas in controls modafinil did not change TMS parameters significantly. Placebo administration did not affect TMS parameters both in patients or controls.ConclusionsNarcolepsy patients with cataplexy showed decreased cortical excitability than normal healthy controls. Single dose modafinil significantly increased motor excitability in narcolepsy patients but had no effect in healthy controls.     

Changes in motor cortex inhibition over time in patients with amyotrophic lateral sclerosis

Abnormal balance between intracortical inhibitory and excitatory mechanisms has been found to contribute to the genesis of motor cortex hyperexcitability in amyotrophic lateral sclerosis (ALS), but data are lacking on the role of these abnormalities in the pathophysiology of the disease. We evaluated the resting motor threshold (RMT), the cortical silent period (CSP) to single-pulse transcranial magnetic stimulation (TMS), early intracortical inhibition (ICI), early intracortical facilitation (ICF) and late ICI to paired-pulse TMS in 40 patients with ALS. These parameters were correlated with disease duration and clinical features. They were also monitored over time in selected patients.The main abnormal TMS findings were: (a). reduced or even absent early and late ICI; six out of 9 patients, with normal early ICI at the first recording, developed abnormal ICI after several months; (b). reduced cortical silent period duration with increasing TMS intensity. ICF and RMT were not affected. Impairment of early and late ICI correlated significantly with disease duration, the diagnostic categories and the clinical evidence of upper motor neuron involvement.The alteration of different cortical inhibitory functions seems to take place with disease progression, rather than being the primary event in the pathogenesis of ALS. The impaired inhibition is considered as being due to both depletion of specific subpopulations of intracortical GABAergic neurons and mechanisms involved in motor cortex reorganization following progressive neuronal loss. Clarification of the importance of these factors in the pathogenesis of the disease may have diagnostic and therapeutic implications.     

Acute and chronic effects of ethanol on cortical excitability.

OBJECTIVE: We designed this study to find out whether 5Hz repetitive transcranial magnetic stimulation (rTMS) would disclose changes in cortical plasticity after acute intake of ethanol and in patients with chronic alcohol consumption. METHODS: Ten stimuli-5Hz-rTMS trains were applied over the primary motor cortex in 10 healthy subjects before and after acute ethanol intake and in 13 patients with chronic ethanol abuse, but negative blood ethanol levels when studied. The motor evoked potential (MEP) amplitude and the cortical silent period (CSP) duration during the course of rTMS trains were measured. Short-interval intracortical inhibition (3ms) and intracortical facilitation (10ms) were studied by paired-pulse TMS in 4 healthy subjects and 4 patients. RESULTS: In healthy subjects before and after acute ethanol intake, 5Hz-rTMS produced a significant increase in the MEP size and CSP duration during rTMS. The first CSP in the train was significantly longer after than before ethanol intake. In patients 5Hz-rTMS failed to produce the normal MEP facilitation but left the CSP increase unchanged. CONCLUSIONS: Acute and chronic ethanol intake alters cortical excitability and short-term plasticity of the primary motor cortex as tested by the MEP size facilitation and CSP lengthening after 5Hz-rTMS. SIGNIFICANCE: This finding suggests that rTMS is a valid tool for investigating the effects of ethanol on cortical plasticity in humans.     

Changes in motor cortical excitability induced by high-frequency repetitive transcranial magnetic stimulation of different stimulation durations.

OBJECTIVE: To investigate the changes in cortical excitability of the human motor cortex induced by high-frequency repetitive transcranial magnetic stimulation (rTMS) of different stimulation durations. METHODS: Twenty healthy subjects participated in the study. Subjects received 20 trains of 10-Hz rTMS at 80% of the resting motor threshold (RMT) intensity with two different stimulation durations (5 and 1.5s) over the motor hot spot for left first dorsal interosseous (FDI) muscle. Electromyographic responses (motor-evoked potentials, MEPs) to single-pulse stimulation, and intracortical inhibition (ICI) and intracortical facilitation (ICF) by paired-pulse stimulation were measured bilaterally in the relaxed FDI muscles before, immediately after, and 30, 60, 90 and 120 min after rTMS. RESULTS: After 5s of 10-Hz rTMS, the mean amplitude of MEP for the stimulated M1 cortex decreased for up to 90min (P=0.002) and that of the unstimulated M1 cortex decreased for up to 60 min (P=0.008). Enhancement of ICI and suppression of ICF were observed and sustained for more than 90 min in both stimulated (P=0.001) and unstimulated (P=0.003) M1 cortex after 5s of 10-Hz rTMS. After 1.5s of 10-Hz rTMS, the mean amplitude of MEP increased in stimulated cortex for up to 120 min (P=0.005). CONCLUSIONS: With different stimulation durations, high-frequency subthreshold rTMS can produce different patterns of long-lasting changes in corticospinal and intracortical excitability in stimulated and unstimulated motor cortex in healthy subjects. SIGNIFICANCE: The results have important implications for the selection of stimulation parameters other than the frequency of rTMS. The clinical application of rTMS for the purpose of motor enhancement should be considered along with the mechanism of different stimulation parameters.     

Interhemispheric effects of high and low frequency rTMS in healthy humans.

OBJECTIVE: We investigated whether repetitive transcranial magnetic stimulation (rTMS) applied to the right motor cortex modified the excitability of the unstimulated left motor cortex. METHODS: Interhemispheric effects of 0.5 and 5 Hz subthreshold rTMS over the right motor cortex were examined by single pulse and paired pulse TMS and by transcranial electrical stimulation (TES) applied to the unstimulated left motor cortex. The effects of (a) 1800 pulses real and sham rTMS with 5 Hz, (b) 180 pulses real and sham rTMS with 0.5 Hz and (c) 1800 pulses real rTMS with 0.5 Hz were studied. RESULTS: Following 5 Hz right motor rTMS motor evoked potential (MEP) amplitudes induced by single pulse TMS over the left motor cortex increased significantly. Intracortical inhibition (ICI) and facilitation (ICF) and MEP amplitudes evoked by TES were unchanged. Sham stimulation had no influence on motor cortex excitability. After 180 pulses right motor cortex rTMS with 0.5 Hz a significant decrease of left motor ICF, but no change in single pulse MEP amplitudes was found. A similar trend was observed with 1800 pulses rTMS with 0.5 Hz. CONCLUSIONS: High frequency right motor rTMS can increase left motor cortex excitability whereas low frequency right motor rTMS can decrease it. These effects outlast the rTMS by several minutes. The underlying mechanisms mediating interhemispheric excitability changes are likely to be frequency dependent.     

Modulation of cortical excitability and interhemispheric inhibition prior to rhythmic unimanual contractions

The objective of this study was to investigate premotor modulation of motor cortical excitability between rhythmic unimanual finger contractions. Applying TMS at rest prior to an anticipated contraction provides a measure of cortical excitability that reflects premotor modulatory drive and is uncontaminated by the alterations in spinal and cortical excitability that occur during muscle activation. We hypothesized that premotor structures contribute to unimanual movement through the modulation of intracortical and interhemispheric inhibitory circuits within the primary motor cortex and that this premotor modulation would be evident at rest between contractions. Thus, we used transcranial magnetic stimulation (TMS) to assess short interval intracortical inhibition (SICI) and interhemispheric inhibition (IHI) in a 500-ms epoch prior to a planned contraction of the right FDI in 10 participants (21.4±1.9 years). These measures of inhibition were made in three different states: (1) at complete rest (with no plan to contract), (2) at rest between rhythmic contractions, and (3) during low level contractions. Cortical excitability was enhanced prior to a contraction and during a contraction compared to at rest (F((2,18))=758.3, p<0.001). IHI was also increased prior to a contraction compared to at rest and during a contraction while SICI was only reduced during a contraction (F((2,38))=30.3, p<0.001).We used this pre-contraction protocol to investigate the cortical mechanisms of unimanual control. However, this protocol would be a useful tool to investigate any neuromuscular adaptation that may occur as a result of altered premotor modulation of cortical excitability, such as neuromuscular fatigue, training and movement disorders.