Reduced intracortical facilitation in patients with cerebellar degeneration

Objectives - Transcranial magnetic stimulation (TMS) was used to study intracortical inhibitory and excitatory phenomena in patients with cerebellar ataxia. Methods - Motor evoked potentials (MEP) following single and paired TMS were recorded from the first dorsal interosseus muscle (FDI) in 15 patients with autosomal-dominant or idiopathic cerebellar ataxia and 15 age matched normal controls. Results- MEP amplitudes after paired TMS with short interstimulus intervals (1-4 ms) showing intracortical inhibition in the control group were not significantly different in the patient group. In contrast, with longer interstimulus intervals (8-20 ms) mean MEP amplitudes were significantly reduced in the patient group, indicating a decrease of intracortical facilitation. The mean postexcitatory inhibition after TMS was also significantly prolonged in the patient group. Conclusion -Our findings support the idea that the cerebellum physiologically exerts a facilitatory influence on the motor cortex which is decreased in patients with a cerebellar degeneration.     

Assessment of cortical excitability using threshold tracking techniques

Conventional paired-pulse transcranial magnetic stimulation (TMS) techniques of assessing cortical excitability are limited by fluctuations in the motor evoked potential (MEP) amplitude. The aim of the present study was to determine the feasibility of threshold tracking TMS for assessing cortical excitability in a clinical setting and to establish normative data. Studies were undertaken in 26 healthy controls, tracking the MEP response from abductor pollicis brevis. Short-interval intracortical inhibition (SICI) occurred up to an interstimulus interval (ISI) of 7-10 ms, with two distinct peaks evident, at ISIs of < or =1 and 3 ms, followed by intracortical facilitation to an ISI of 30 ms. Long-interval intracortical inhibition (LICI) occurred at ISIs of 50-300 ms, peaking at 150 ms. The present study has confirmed the effectiveness of the threshold tracking TMS technique in reliably and reproducibly measuring cortical excitability. Simultaneous assessment of upper and lower motor neuronal function with threshold tracking techniques may help to determine the site of disease onset and patterns of progression in neurodegenerative diseases.     

Intracortical excitability in patients with relapsing–remitting and secondary progressive multiple sclerosis

We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing–remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients’ TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.     

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.     

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.     

Intracortical inhibition and facilitation are impaired in patients with early Parkinson''s disease: a paired TMS study

Twelve patients with early Parkinson's disease (PD), none of whom had received any previous L-DOPA treatment, but using other antiparkinsonian drugs, were studied using transcranial magnetic stimulation (TMS). Contralateral and ipsilateral hemispheres were examined, with a focus on the more pronounced parkinsonian symptoms. The conditioning-test TMS paradigm (with a subthreshold conditioning stimulus and a suprathreshold test stimulus) was used through a stimulating round coil. Paired stimuli of short (3, 5 and 7 ms), medium (10, 15 and 20 ms), and long (100, 150, 200 and 250 ms) interstimulus intervals (ISI) were pseudo-randomly mixed with a single stimulus. The first interosseus muscle was used for the motor-evoked potential recordings. Ten healthy subjects (age and sex matched) were studied in the same manner to obtain normative data. When both groups were compared, the significant difference (reduction of the intracortical inhibition and facilitation) between the PD patients and the control group was found at the short and the medium ISI (3, 5, 7, 10, 15 and 20 ms) in both hemispheres (P < 0.05). The longer ISI produced non-significant differences between the two groups in intracortical excitability. There was a non-significant difference in the motor threshold. In conclusion, it can be supposed that both intracortical inhibition and facilitation are impaired in patients with early PD using other antiparkinsonian treatments than L-DOPA or dopamine agonists.     

Different short-term modulation of cortical motor output to distal and proximal upper-limb muscles during painful sensory nerve stimulation

The pattern of upper-limb muscle activation following painful stimulation has not been clarified in detail. We investigated the short-term inhibitory and excitatory effects of painful electrical digital stimulation on the motoneuron pools of distal and proximal upper-limb muscles. Transcranial magnetic stimulation (TMS) was used as test stimulus, and painful digital nerve stimulation as conditioning stimulus for motor evoked potential (MEP) recordings over the abductor digiti minimi (ADM), abductor pollicis brevis (APB), biceps brachii (BB), and deltoid muscles. Inhibition of the conditioned MEP response was most prominent in the distal muscles, whereas BB and deltoid muscles were only weakly inhibited. The mean MEP response over APB decreased with painful cutaneous stimuli, showing maximum inhibition (by 82%) at interstimulus intervals (ISIs) of 50 ms. Inhibition in the ADM was maximal (49%) but less pronounced at an ISI of 40 ms. The BB and deltoid muscles showed inhibition by 25% and 29%, respectively. Significant facilitation was present in BB and deltoid muscles by 43% and 41% at an ISI of 100 ms, but not in the smaller hand muscles. The observed pattern of upper-limb muscle activation corresponds to the protective withdrawal reflex and the neuronal basis of the observed short-term modulation of motor activity is compatible with a spinal or brainstem pathway.     

Intracortical inhibition and facilitation upon awakening from different sleep stages: a transcranial magnetic stimulation study

Intracortical facilitation and inhibition, as assessed by the paired-pulse transcranial magnetic stimulation technique with a subthreshold conditioning pulse followed by a suprathreshold test pulse, was studied upon awakening from REM and slow-wave sleep (SWS). Ten normal subjects were studied for four consecutive nights. Intracortical facilitation and inhibition were assessed upon awakening from SWS and REM sleep, and during a presleep baseline. Independently of sleep stage at awakening, intracortical inhibition was found at 1-3-ms interstimulus intervals and facilitation at 7-15-ms interstimulus intervals. Motor thresholds were higher in SWS awakenings, with no differences between REM awakenings and wakefulness, while motor evoked potential amplitude to unconditioned stimuli decreased upon REM awakening as compared to the other conditions. REM sleep awakenings showed a significant increase of intracortical facilitation at 10 and 15 ms, while intracortical inhibition was not affected by sleep stage at awakening. While the dissociation between motor thresholds and motor evoked potential amplitudes could be explained by the different excitability of the corticospinal system during SWS and REM sleep, the heightened cortical facilitation upon awakening from REM sleep points to a cortical motor activation during this stage.     

Inverse correlation of intracortical inhibition and brain-stem inhibition in humans.

OBJECTIVE: To determine whether intracortical inhibition and the conditioned blink reflex R2 inhibition correlate in healthy subjects. BACKGROUND: In Parkinson's disease and in focal dystonia the intracortical inhibition and the conditioned blink reflex R2 inhibition are abnormally weak. METHODS: In 10 healthy humans (average age 25.7 years) we investigated the intracortical excitability of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation with a conditioning pulse (90% active motor threshold) followed by a pulse of 120% resting motor threshold after an interstimulus interval ranging from 1 to 30 ms. We investigated the blink reflex with two suprathreshold stimuli over the supraorbital nerve and EMG recording from the orbicularis oculi ipsilateral to electrical stimulation, the interstimulus intervals were 100, 250 and 500 ms. RESULTS: The intracortical inhibition, but not the intracortical facilitation, was inversely and significantly correlated with the R2 inhibition on the side of transcranial stimulation, but not with the contralateral R2 inhibition. CONCLUSIONS: The correlation of intracortical inhibitory interneurons and ipsilateral blink reflex interneurons may indicate a common influence, possibly from the basal ganglia, on either circuit, or a direct influence of cortical circuits on brain-stem circuits via corticopontine pathways.     

The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI). A subthreshold conditioning stimulus (CS) was given to PMd 2.0-5.2 ms after the TS at intensities of 50-, 70-, or 90% of TS. The CS to PMd facilitated the MEP evoked by TS over M1(HAND) at interstimulus intervals (ISI) of 2.4 or 2.8 ms. There was a second facilitatory peak at ISI of 4.4 ms. PMd-to-M1(HAND) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over lateral prefrontal cortex. Together our results indicate that our dsTMS paradigm probes a short-latency facilitatory PMd-to-M1(HAND) pathway. The temporal pattern of MEP facilitation suggests a PMd-to-M1(HAND) route that targets intracortical M1(HAND) circuits involved in the generation of indirect corticospinal volleys. This paradigm opens up new possibilities to study context-dependent intrahemispheric PMd-to-M1(HAND) interactions in the intact human brain.     

Early and late intracortical inhibition in juvenile myoclonic epilepsy

PURPOSE: We investigated 15 patients with juvenile myoclonic epilepsy (JME) by subjecting them to single and paired transcranial magnetic stimulation to test the hypothesis that motor cortical inhibition may be abnormal in this form of benign epilepsy. METHODS: Different conditioning paradigms of paired transcranial magnetic stimulation were used with interstimulus intervals (ISIs) of varying lengths (1 to 400 milliseconds) to investigate changes in balance between excitatory and inhibitory intracortical circuits. RESULTS: Motor evoked potential (MEP) inhibition at ISIs of 1 to 4 milliseconds was significantly lower in JME patients than in age-matched healthy controls (p < 0.001), whereas no significant differences in MEP inhibition were noted at long ISIs (100 to 150 milliseconds). This pattern was observed in both hemispheres in seven of seven patients studied bilaterally and was present in both treated and untreated patients. There were no group differences between JME patients and controls in intracortical facilitation, motor threshold, MEP amplitude, and cortical silent period. CONCLUSIONS: We documented a different pattern of MEP inhibition in JME patients, suggesting impaired functioning of inhibitory interneuronal circuits, which may account for the hyperexcitability of the motor system in this form of epilepsy.     

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.     

Low-intensity repetitive paired associative stimulation targeting the motor hand area at theta frequency causes a lasting reduction in corticospinal excitability

ObjectiveSub-motor threshold 5 Hz repetitive paired associative stimulation (5 Hz-rPAS_25ms) produces a long-lasting increase in corticospinal excitability. Assuming a spike-timing dependent plasticity-like (STDP-like) mechanism, we hypothesized that 5 Hz-rPAS at a shorter inter-stimulus interval (ISI) of 15 ms (5 Hz-rPAS_15ms) would exert a lasting inhibitory effect on corticospinal excitability.Methods20 healthy volunteers received two minutes of 5 Hz-rPAS_15ms. Transcranial magnetic stimulation (TMS) was applied over the motor hotspot of the right abductor pollicis brevis muscle at 90% active motor threshold. Sub-motor threshold peripheral electrical stimulation was given to the left median nerve 15 ms before each TMS pulse. We assessed changes in mean amplitude of the unconditioned motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and cortical silent period (CSP) before and for 60 minutes after 5-Hz rPAS_15ms.ResultsSubthreshold 5-Hz rPAS_15ms produced a 20–40% decrease in mean MEP amplitude along with an attenuation in SAI, lasting at least 60 minutes. A follow-up experiment revealed that MEP facilitation was spatially restricted to the target muscle.ConclusionsSubthreshold 5-Hz rPAS_15ms effectively suppresses corticospinal excitability. Together with the facilitatory effects of subthreshold 5-Hz rPAS_25ms (Quartarone et al., J Physiol 2006;575:657–670), the results show that sub-motor threshold 5-Hz rPAS induces STDP-like bidirectional plasticity in the motor cortex.SignificanceThe results of the present study provide a new short-time paradigm of long term depression (LTD) induction in human sensory-motor cortex.     

Zonisamide Changes Unilateral Cortical Excitability in Focal Epilepsy Patients

Background and Purpose

To evaluate changes in cortical excitability induced by zonisamide (ZNS) in focal epilepsy patients.

Methods

Twenty-four drug-naїve focal epilepsy patients (15 males; overall mean age 29.8 years) were enrolled. The transcranial magnetic stimulation parameters obtained using two Magstim 200 stimulators were the resting motor threshold, amplitude of the motor-evoked potential (MEP), cortical silent period, short intracortical inhibition, and intracortical facilitation. These five transcranial magnetic stimulation parameters were measured before and after ZNS, and the findings were compared.

Results

All 24 patients were treated with ZNS monotherapy (200-300 mg/day) for 8-12 weeks. After ZNS, MEP amplitudes decreased (-36.9%) significantly in epileptic hemispheres (paired t-test with Bonferroni''s correction for multiple comparisons, p<0.05), whereas the mean resting motor threshold, cortical silent period, short intracortical inhibition, and intracortical facilitation were unchanged (p>0.05). ZNS did not affect cortical excitability in nonepileptic hemispheres.

Conclusions

These findings suggest that ZNS decreases cortical excitability only in the epileptic hemispheres of focal epilepsy patients. MEP amplitudes may be useful for evaluating ZNS-induced changes in cortical excitability.     

Reduced excitability of the motor cortex in untreated patients with de novo idiopathic "grand mal" seizures.

OBJECTIVES: Transcranial magnetic stimulation (TMS) was used to investigate motor cortex excitability, intracortical excitatory, and inhibitory pathways in 18 patients having experienced a first "grand mal" seizure within 48 hours of the electrophysiological test. All had normal brain MRI, and were free of any treatment, drug, or alcohol misuse. Results were compared with those of 35 age matched normal volunteers. METHODS: The following parameters of responses to TMS were measured: motor thresholds at rest and with voluntary contraction, amplitudes of responses, cortical silent periods, and responses to paired pulse stimulation with interstimulus intervals of 1 to 20 ms. RESULTS: In patients, there were significantly increased motor thresholds with normal amplitudes of motor evoked potentials (MEPs), suggesting decreased cortical excitability. Cortical silent periods were not significantly different from those of normal subjects. Paired TMS with short interstimulus intervals (1-5 ms) induced normal inhibition of test MEPs, suggesting preserved function of GABAergic intracortical inhibitory interneurons. On the contrary, the subsequent period of MEP facilitation found in normal subjects (ISIs of 6-20 ms) was markedly reduced in patients. This suggests the existence of abnormally prolonged intracortical inhibition or deficient intracortical excitation. In nine patients retested 2 to 4 weeks after the initial seizure, these abnormalities persisted, although to a lesser extent. CONCLUSION: The present findings together with abnormally high motor thresholds could represent protective mechanisms against the spread or recurrence of seizures.     

Cortical excitability and sleep deprivation: a transcranial magnetic stimulation study

The objective was to assess the changes in cortical excitability after sleep deprivation in normal subjects. Sleep deprivation activates EEG epileptiform activity in an unknown way. Transcranial magnetic stimulation (TMS) can inform on the excitability of the primary motor cortex. Eight healthy subjects (four men and four women) were studied. Transcranial magnetic stimulation (single and paired) was performed by a focal coil over the primary motor cortex, at the "hot spot" for the right first dorsal interosseous muscle. The following motor evoked potential features were measured: (a) active and resting threshold to stimulation; (b) duration of the silent period; (c) amount of intracortical inhibition on paired TMS at the interstimulus intervals of 2 and 3 ms and amount of facilitation at interstimulus intervals of 14 and 16 ms. The whole TMS session was repeated after a sleep deprivation of at least 24 hours. After the sleep deprivation, the threshold to stimulation (in the active and resting muscle), as well as the silent period, did not change significantly. By contrast, the paired stimulus study showed a significant (p<0.05) reduction in both intracortical inhibition and facilitation. Thus, TMS showed that sleep deprivation is associated with changes in inhibition-facilitation balance in the primary motor cortex of normal subjects. These changes might have a link with the background factors of the "activating" effects of sleep deprivation.     

Impaired sensorimotor integration in cervical dystonia: a study using transcranial magnetic stimulation and muscle vibration.

The authors studied the effects of sensorimotor integration (corticocortical inhibition and facilitation during muscle vibration [MV]) in dystonic patients. Eleven patients with cervical dystonia and 11 age-matched healthy control subjects were enrolled in the study. They were examined using transcranial magnetic stimulation (TMS) and tonic proprioceptive input (MV). Paired-pulse transcranial magnetic stimulation was done at interstimulus intervals of 3 msec (intracortical inhibition) and 13 msec, the intensity of the conditioning stimulus was 70% of the motor threshold, and the test stimulus was 120%. Motor evoked potentials were recorded from the vibrated extensor carpi radialis muscle and its antagonist, the flexor carpi radialis. Duration of MV trains (80 Hz; amplitude, 0.5 mm) was 4 seconds. The authors found differences between patients and healthy control subjects during MV only. Intracortical inhibition was pronounced significantly only in control subjects, whereas intracortical facilitation was significant in patients only (P < 0.05). Furthermore, the significant reduction of motor evoked potentials at 13-msec interstimulus intervals, which can be found in healthy subjects frequently, was observed in one dystonia patient only. The results of the current study suggest that sensorimotor integration is impaired in cervical dystonia, probably by an altered control of proprioceptive (vibratory) input.     

Reduced cortical inhibition in first-episode schizophrenia

Disturbances in cortico-cortical and cortico-subcortical circuits in schizophrenia have been described by previous neuroimaging and electrophysiological studies. Transcranial magnetic stimulation (TMS) provides a neurophysiological technique for the measurement of cortical excitability, especially of the motoneural system. Previous studies using paired-pulse TMS to investigate short-interval cortical inhibition (SICI) and intracortical facilitation (ICF), mainly involving chronic schizophrenia patients, have been inconsistent and only one study in first-episode patients has been conducted so far. We assessed SICI (interstimulus interval, ISI, 3 milliseconds, ms) and ICF (ISI 7 ms) in 29 first-episode schizophrenia patients (FE-SZ) with limited exposure to antipsychotic treatment against measures of 28 healthy controls (HC). Amplitudes of motor evoked potentials (MEPs) were measured from the left and right first dorsal interosseus muscle (FDI). The conditioning stimulus was set at 80% intensity of resting motor threshold (RMT) and the test stimulus (TS) was set at an intensity that produced an MEP amplitude of about 1 mV. For SICI conditions, FE-SZ demonstrated significantly higher MEP amplitudes from left motor cortex (right FDI) compared to HC, and for MEPs from right motor cortex (left FDI) a similar trend was observable (FE-SZ 41% vs. HC 21% of TS, p=0.017 for left motor cortex, and FE-SZ 59% vs. HC 31% of TS, p=0.059 for right motor cortex; Mann-Whitney U-test). No significant difference in MEPs could be detected for ICF on either hemisphere. In addition, there was no difference in left and right RMT comparing patients and control subjects. Our result of a reduced SICI in a large sample of well characterized first-episode schizophrenia patients suggests that a GABAergic deficit may be involved in schizophrenic pathophysiology, already early in the disease course, supporting the intracortical dysconnectivity hypothesis.     

Effect of paired transcranial magnetic stimulation on the cortical silent period

Objective. To investigate the behaviour of silent period (SP) during paired magnetic cortical stimulation. Background. Paired cortical magnetic stimulation is known to inhibit or facilitate motor evoked potentials (MEPs), but no attention has been paid to its effect on SP. Methods. SP was measured in the contracted first dorsal interosseus muscle after paired cortical stimuli at given interstimulus intervals (ISIs) in eight healthy subjects. Test stimulus intensity was fixed at 110% of resting threshold (RT), while three levels of conditioning stimulus intensities at 40%, 65% and 90% RT were separately employed. We also examined the effect of progressively increasing the test stimulus intensity (120–150 RT) on SP while maintaining stable conditioning stimulus intensity. Results. 65% RT conditioning stimulus shortened the SP at 1–3 ms ISIs with MEP size reduction, and prolonged the SP at 15–20 ms ISIs without affecting MEP size. 90% RT conditioning stimulus showed only SP prolongation, while 40% RT showed only SP shortening at 1 ms ISI. The SP shortening at 2 ms ISI was the most evident with 120% RT test stimulus, but without correlation with the MEP size. The SP prolongation at 15 ms ISI was maximal with 110% RT test stimulus and then almost abolished with 150% RT. The SP shortening at short intervals might be due not only to spinal but also to suprasegmental mechanisms, conceivably mediating cortical excitatory drive to the corticospinal tract. The SP prolongation at intermediate intervals might be due to activation of slowly conducting, intra- or sub-cortical polysynaptic pathways exerting a facilitatory drive on the cortical inhibitory interneurons.     

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation

Objective

Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS (‘magnetic-PAS’) on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle.