Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation

BACKGROUND: Cortical inhibition (CI) deficits have been proposed as a pathophysiologic mechanism in schizophrenia. This study employed 3 transcranial magnetic stimulation (TMS) paradigms to assess CI in patients with schizophrenia. Paired-pulse TMS involves stimulating with a lower-intensity pulse a few milliseconds before a higher-intensity pulse, thereby inhibiting the size of the motor evoked potential produced by the higher-intensity pulse. In the cortical silent period paradigm, inhibition is reflected by the silent period duration (ie, the duration of electromyographic activity cessation following a TMS-induced motor evoked potential). Transcallosal inhibition involves stimulation of the contralateral motor cortex several milliseconds prior to stimulation of the ipsilateral motor cortex, inhibiting the size of the motor evoked potential produced by ipsilateral stimulation. METHODS: We measured CI using these 3 paradigms in 15 unmedicated patients with schizophrenia (14 medication-naive and 1 medication-free for longer than 1 year) (13 were in the transcallosal inhibition paradigm), 15 medicated patients with schizophrenia (11 taking olanzapine, 1 risperidone, 1 quetiapine, 1 methotrimeprazine + perphenazine, 1 quetiapine + loxapine), and 15 healthy controls. RESULTS: Unmedicated patients demonstrated significant CI deficits compared with healthy controls across all inhibitory paradigms whereas medicated patients did not (at all inhibitory intervals, paired-pulse TMS: controls = 59.9%, medicated = 44.3%, unmedicated = 28.7%; cortical silent period: controls = 55.0 milliseconds, medicated = 60.4 milliseconds, unmedicated = 39.7 milliseconds; transcallosal inhibition: controls = 33.6%, medicated = 23.7%, unmedicated = 10.4%; P<.05). CONCLUSIONS: These results suggest that schizophrenia is associated with deficits in CI and that antipsychotic medications may increase CI.     

Focal transcranial magnetic stimulation of motor cortex evokes bilateral and symmetrical silent periods in human masseter muscles.

OBJECTIVE: To determine whether a single hemisphere exerts distinct inhibitory influences over masseter muscles on each side, and to compare features of the masseter cortical silent period (CSP) evoked by transcranial magnetic stimulation (TMS) with previous reports from limb and other cranial muscles. METHODS: Focal TMS was applied over the motor cortex jaw area in 14 normal subjects. In one experiment, TMS intensity was constant (1.1 or 1.3x active motor threshold, T) and masseter muscle activation varied from 10% to 100% of maximal. In another experiment, muscle activation was constant (20% maximal) and TMS intensity varied from 0.7 to 1.3T. RESULTS: In all subjects, TMS evoked a silent period of similar duration in masseter muscles on both sides. Masseter CSP duration increased at higher TMS intensities, but was not affected by muscle activation level or the size of the excitatory response evoked by TMS. Weak TMS produced a bilateral CSP without short-latency excitation. The masseter CSP was short ( approximately 100ms at 1.3T), yet this was not due to maintenance of excitatory drive from the unstimulated hemisphere, as the masseter CSP was not prolonged with dual-hemisphere TMS. CONCLUSIONS: Intracortical inhibitory circuits activated by TMS have a relatively weak effect on corticotrigeminal neurons supplying masseter, and effects are equivalent for corticobulbar efferents directed to contralateral and ipsilateral masseter motoneuron pools. SIGNIFICANCE: Trigeminally innervated masseter muscles exhibit weak, bilaterally symmetric inhibition following focal TMS. This method can be used to investigate abnormalities of intracortical inhibition in movement disorders or focal lesions affecting the masticatory muscles in humans.     

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.     

Analysis of stimuli triggering attacks of paroxysmal dystonia induced by exertion

In a patient with a familial form of paroxysmal exertion induced dyskinesia (PED), the efficacy of different stimuli and manoeuvres in triggering dystonic attacks in the arm was studied. As a new approach, transcranial magnetic stimulation (TMS) of the motor cortex was used to trigger motor paroxysms and to monitor cortical excitability during attacks. Motor paroxysms could be provoked by muscle vibration, passive movements, TMS, magnetic stimulation of the brachial plexus, and electrical nerve stimulation. Sham stimulation over the motor cortex and thermal and tactile cutaneous stimuli were ineffective in triggering attacks. It is concluded that dystonic attacks are triggered by proprioceptive afferents rather than cutaneous stimuli or the descending motor command itself. Outside the attacks, motor cortical excitatory and inhibitory neuronal mechanisms as assessed by TMS (response threshold and amplitudes, duration of the contralateral and ipsilateral silent period, corticocortical inhibition, and facilitation) were normal, which underlines the paroxysmal character of the disorder.     

“Gating” of human short-latency somatosensory evoked cortical responses during execution of movement. A high resolution electroencephalography study

The present study aimed at investigating gating of median nerve somatosensory evoked cortical responses (SECRs), estimated during executed continuous complex ipsilateral and contralateral sequential finger movements. SECRs were modeled with an advanced high resolution electroencephalography technology that dramatically improved spatial details of the scalp recorded somatosensory evoked potentials. Integration with magnetic resonance brain images allowed us to localize different SECRs within cortical areas. The working hypothesis was that the gating effects were time varying and could differently influence SECRs. Maximum statistically significant (p<0.01) time-varying gating (magnitude reduction) of the short-latency SECRs modeled in the contralateral primary motor and somatosensory and supplementary motor areas was computed during the executed ipsilateral movement. The gating effects were stronger on the modeled SECRs peaking 30–45 ms (N30–P30, N32, P45–N45) than 20–26 ms (P20–N20, P22, N26) post-stimulus. Furthermore, the modeled SECRs peaking 30 ms post-stimulus (N30–P30) were significantly increased in magnitude during the executed contralateral movement. These results may delineate a distributed cortical sensorimotor system responsible for the gating effects on SECRs. This system would be able to modulate activity of SECR generators, based on the integration of afferent somatosensory inputs from the stimulated nerve with outputs related to the movement execution.     

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.     

Pseudo-bilateral hand motor responses evoked by transcranial magnetic stimulation in patients with deep brain stimulators.

OBJECTIVES: In 3 of 5 patients with dystonia and bilaterally implanted deep brain stimulating electrodes, focal transcranial magnetic stimulation (TMS) of one motor cortex elicited bilateral hand motor responses. The aim of this study was to clarify the origin of these ipsilateral responses. METHODS: TMS and electrical stimulation of corticospinal fibres by the implanted electrodes were performed and the evoked hand motor potentials were analysed. RESULTS: In comparison with responses elicited by contralateral motor cortex stimulation, ipsilateral responses were smaller in amplitude (3.0+/-1.4 versus 5.8+/-1.5 mV), had shorter peak latencies (first negative peak: 20.9+/-0.8 versus 25.1+/-0.4 ms) and were followed by a shorter-lasting silent period (46+/-4 versus 195+/-35 ms). Ipsilateral responses following TMS had similar peak latencies to responses elicited subcortically by deep brain stimulation (DBS) (20.4+/-0.9 ms). CONCLUSIONS: Hand motor responses ipsilateral to TMS result from a subcortical activation of corticospinal fibres, via the implanted electrode in the other hemisphere, secondary to currents induced by TMS in subcutaneous wire loops that underlie the magnetic coil. Studies of TMS in patients with DBS have to take this potential source of confounding into account.     

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.     

CENTRAL EFFECT OF BOTULINUM TOXIN TYPE A IN HUMANS

This study investigated the changes in the cortical excitability with a paired-pulse transcranial magnetic stimulation (TMS) model after a botulinum toxin type A (BTA) injection in normal humans. Ten healthy subjects were enrolled in the study, which involved applying paired TMS to the motor cortex and recording the motor evoked potentials (MEP) before and after the BTA injection. BTA (2.5 mouse units) was injected into the right extensor digitorium brevis muscle. The amplitudes of MEP during rest and the cortical silent period (CSP) for the period of the tonic muscle contraction were measured at an interstimulus interval (ISI) of 3 ms and 20 ms. One month and three months after BTA injection, the level of intracortical inhibition increased significantly at an ISI of 3 ms and the intracortical facilitation decreased at an ISI of 20 ms. The duration of CSP shortened significantly at an ISI of 3 ms 1 month after BTA injection, which was also shortened significantly at an ISI of 20 ms. These findings were maintained until 3 months after the injection. It was concluded that cortical excitability could be modified by BTA injection in normal humans.     

Evidence for normal intracortical inhibitory recruitment properties in cervical dystonia

ObjectiveDystonia is associated with reduced intracortical inhibition as measured by the cortical silent period (cSP); however, this may be due to abnormal cSP threshold or input-output properties. This study evaluated cSP recruitment properties in people with cervical dystonia (CD).MethodsBilateral electromyographic recordings were collected in the upper trapezius muscle in response to transcranial magnetic stimulation of the left and right primary motor cortex in a group with CD (n = 19) and controls (n = 21). cSP threshold, cSP input-output properties at stimulation intensities from 1 to 1.4x the cSP threshold, ipsilateral silent period duration (iSP) and timing and magnitude of the contralateral and ipsilateral motor evoked potential (MEP) were assessed.ResultsThe cSP threshold, input-output properties, and contralateral MEP magnitude were not significantly different between groups (all p > 0.07). Hemispheric symmetry was present in the control group while the CD group had reduced iSP (p < 0.01) and a trend for reduced ipsilateral MEP response (p = 0.053) in the left hemisphere.ConclusionsRecruitment properties of intracortical inhibition are similar between control and CD groups. Transcallosal inhibition is asymmetric between hemispheres in people with CD.SignificanceEvidence of normal intracortical inhibition recruitment properties challenge the commonly held view that cortical inhibition is reduced in dystonia.     

Increased Cortical Excitability in Female Migraineurs: A Transcranial Magnetic Stimulation Study Conducted in the Preovulatory Phase

Background and PurposeThe cerebral cortex has been the focus of investigations of the pathogenesis of migraine for a long time. Transcranial magnetic stimulation (TMS) is a safe and effective technique for evaluating cortex excitability. Previous studies of the duration of the cortical silent period (CSP)—a measure of intracortical inhibition—in migraine patients have yielded conflicting results. We aimed to characterize cortical excitability by applying TMS to female migraineurs during the preovulatory phase of the menstrual cycle, in order to eliminate the effects of variations in sex hormones.MethodsWe enrolled 70 female subjects: 20 migraine with aura (MA) patients, 20 migraine without aura (MO) patients, and 30 healthy controls. We measured the CSP, resting motor threshold (rMT), and motor evoked potential (MEP) induced by TMS to evaluate cortical excitability during the preovulatory phase of the menstrual cycle.ResultsThe CSP was shorter in MA patients (88.93±3.82 ms, mean±SEM) and MO patients (86.98±2.72 ms) than in the control group (109.06±2.85 ms) (both p=0.001), and did not differ significantly between the MA and MO groups (p=0.925). The rMT did not differ significantly among the groups (p=0.088). MEP_max was higher in MA patients than in healthy controls (p=0.014), while that in MO patients did not differ from those in MA patients and healthy controls (p=0.079 and p=0.068).ConclusionsWe detected a shorter CSP in both MA and MO patients. This finding may indicate the presence of motor cortex hyperexcitability, which is probably due to reduced GABAergic neuronal inhibition in migraine.     

Crossed and direct effects of digital nerves stimulation on motor evoked potential: a study with magnetic brain stimulation

We studied the influence of contralateral and ipsilateral cutaneous digital nerve stimulation on motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation (TMS). We tested the effect of different magnetic stimulus intensities on MEPs recorded from the thenar eminence (TE) muscles of the right hand while an electrical conditioning stimulus was delivered to the second finger of the same hand with an intensity four times above the sensory threshold. Amplitude decrement of conditioned MEPs as a function of magnetic stimulus intensity was observed. The lowest TMS stimulus intensity produced the largest decrease in conditioned MEPs. Moreover, we investigated the effects of ipsilateral and contralateral electrical digital stimulation on MEPs elicited in the right TE and biceps muscle using an intensity 10% above the threshold. Marked MEP inhibition in TE muscles following both ipsilateral and contralateral digital stimulation is the main finding of this study. The decrease in conditioned MEP amplitude to ipsilateral stimulation reached a level of 50% of unconditioned MEP amplitude with the circular coil and 30% with the focal coil. The amplitude of conditioned MEPs to contralateral digital stimulation showed a decrease of 60% with the circular coil and more than 50% with the focal coil. The onset of the inhibitory effect of contralateral stimulation using the focal coil occurred at a mean of 15 ms later than that of ipsilateral stimulation. No MEP inhibition was observed when recording from proximal muscles. Ipsilateral and contralateral digital stimulation had no effect on F wave at appropriate interstimulus intervals, where the main MEP suppression was noted. We stress the importance of selecting an appropriate test stimulus intensity to evaluate MEP inhibition by digital nerves stimulation. Spinal and cortical sites of sensorimotor integration are adduced to explain the direct and crossed MEP inhibition following digital nerves stimulation.     

Changes in corticomotor excitation and inhibition during prolonged submaximal muscle contractions

Changes in motor evoked potential (MEP) amplitude, post-MEP silent period duration, and interpolated twitch torque were measured using transcranial magnetic (TMS) and electrical (TES) stimulation during a 20% maximum voluntary contraction of the elbow flexors sustained to exhaustion. TMS- and TES-induced MEP amplitude increased progressively over the contraction period up until the point of exhaustion. The TMS-induced silent period was prolonged only during the second half of the contraction period, the time course being different from that of the MEP responses, whereas the TES-induced silent period did not change. The findings indicate that corticomotor excitability increases during a sustained submaximal voluntary contraction and that, as fatigue develops, there is a progressive buildup of intracortical inhibition. This may represent a mechanism whereby corticomotor output is maintained at an appropriate level to preserve optimal motor unit firing frequencies during a fatiguing contraction. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20:1158–1166, 1997     

Impact of pulse duration in single pulse TMS

Objective

The intensity of transcranial magnetic stimulation (TMS) is typically adjusted by changing the amplitude of the induced electrical field, while its duration is fixed. Here we examined the influence of two different pulse durations on several physiological parameters of primary motor cortex excitability obtained using single pulse TMS.

Methods

A Magstim Bistim² stimulator was used to produce TMS pulses of two distinct durations. For either pulse duration we measured, in healthy volunteers, resting and active motor thresholds, recruitment curves of motor evoked potentials in relaxed and contracting hand muscles as well as contralateral (cSP) and ipsilateral (iSP) cortical silent periods.

Results

Motor thresholds decreased by 20% using a 1.4 times longer TMS pulse compared to the standard pulse, while there was no significant effect on threshold adjusted measurements of cortical excitability. The longer pulse duration reduced pulse-to-pulse variability in cSP.

Conclusions

The strength of a TMS pulse can be adjusted both by amplitude or pulse duration. TMS pulse duration does not affect threshold-adjusted single pulse measures of motor cortex excitability.

Significance

Using longer TMS pulses might be an alternative in subjects with very high motor threshold. Pulse duration might not be relevant as long as TMS intensity is threshold-adapted. This is important when comparing studies performed with different stimulator types.     

Facilitation of rhythmic events in progressive myoclonus epilepsy: a transcranial magnetic stimulation study.

Twelve subjects with progressive myoclonus epilepsy (PME) were studied with transcranial magnetic stimulation (TMS), using single and paired magnetic stimuli at different interstimulus intervals (ISIs), and polygraphic recording. Motor threshold (T) and silent period (SP) were normal. Paired TMS showed a loss of inhibition at 100-150 ms ISI and a marked facilitation at 50 ms ISI of conditioned motor evoked potential (MEP). Polygraphic analysis showed 20 Hz oscillatory activity over the sensorimotor area coupled to contralateral myoclonic jerks. These findings suggest a condition of increased supraspinal excitability and support the evidence of a cortical rhythm in the range of 20 Hz. No direct evidence exists that these findings are mediated by the same intracortical pathway. Furthermore, the normal SP and T suggest that the abnormal excitability is not a constant feature but is evident during rhythmic events.     

Cortical mechanisms mediating the inhibitory period after magnetic stimulation of the facial motor area

We studied the silent period (SP) that interrupts voluntary electromyographic activity (EMG) in facial muscles, after transcranial magnetic stimulation (TMS), in normal subjects. High-intensity magnetic stimulation with a 12-cm round coil centered at the vertex induced a long-lasting SP (215 ms), whereas supramaximal stimulation of the facial nerve only induced a short (< 20 ms) and incomplete EMG suppression, and cutaneous stimuli had no inhibitory effect at all. Cutaneous trigeminal stimulation delivered after TMS evoked blink-like reflexes, showing that facial motoneurons were not inhibited during the SP. Simultaneous recordings from perioral muscles (large cortical representation) and from orbicularis oculi and masseter muscles (small cortical representation) showed SPs of identical duration. Focal stimuli with a figure-of-eight coil showed that positioning of the coil was critical and that the optimal scalp sites for evoking the largest motor potentials and longest SPs coincided. Low-intensity stimulation occasionally elicited short SPs without a preceding motor potential. We conclude that the SP induced in facial muscles by TMS results from the excitation of cortical inhibitory interneurons surrounding the upper motoneurons. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 418–424, 1997.     

The silent period of the thenar muscles to contralateral and ipsilateral deep brain stimulation.

OBJECTIVE: We aimed at characterizing the silent period induced in hand muscles by subcortical stimulation through electrodes implanted on the subthalamic nucleus for deep brain stimulation (STN-DBS). METHODS: In 10 patients with Parkinson's disease, we analyzed the inhibitory effects induced in the contralateral and ipsilateral thenar muscles by STN-DBS of varying stimulus intensity and strength of muscle contraction. RESULTS: Both, the contralateral silent period (CSP) and the ipsilateral silent period (ISP) were induced by stimuli at an intensity subthreshold for eliciting a contralateral motor evoked potential (MEP) and were composed of two phases. With a stimulus intensity of 120% of active threshold and a strength of 20%, the first CSP had a mean onset latency of 38.0 +/- 2.9 ms and a mean duration of 37.7 ms +/- 2.8 ms, and the second CSP had a mean onset latency of 90.6 +/- 18.5 ms and a mean duration of 53.4 +/- 6.3 ms. The first ISP had a mean onset latency of 34.9 +/- 4.3 ms and a mean duration of 12.5 +/- 3.4 ms, and the second ISP had a mean onset latency of 76.3 +/- 10.1 ms and a mean duration of 23.1 +/- 9.0 ms. The duration of both phases of the CSP increased with increasing the stimulus intensity and the burst separating the two phases of the CSP increased in size with increasing the strength of muscle contraction or the stimulus intensity. No ipsilateral MEP was observed in any patient at any strength or stimulus intensity. CONCLUSION: Our results indicate that the silent period induced by STN-DBS has specific physiological mechanisms that differ from those of the silent period induced by cortical transcranial magnetic stimulation. SIGNIFICANCE: The induction of ISP by stimulation of the motor tract at a point caudal to the corpus callosum indicates that non-callosal pathways are capable of generating ISP.     

The dual nature of time preparation: neural activation and suppression revealed by transcranial magnetic stimulation of the motor cortex

Single-pulse transcranial magnetic stimulations (TMSs) of the motor cortex (M1) were performed in order to decipher the neural mechanisms of time preparation. We varied the degree to which it was possible to prepare for the response signal in a choice reaction time (RT) task by employing either a short (500 ms) or a long (2500 ms) foreperiod in separate blocks of trials. Transcranial magnetic stimulations were delivered during these foreperiods in order to study modulations in both the size of the motor evoked potential (MEP) and the duration of the silent period (SP) in tonically activated response agonists. Motor evoked potential area and silent period duration were assumed to reflect, respectively, the excitability of the cortico-spinal pathway and the recruitment of inhibitory cortical interneurons. Shorter reaction times were observed with the shorter foreperiod, indicating that a better level of preparation was attained for the short foreperiod. Silent period duration decreased as time elapsed during the foreperiod and this decrement was more pronounced for the short foreperiod. This result suggests that time preparation is accompanied by a removal of intracortical inhibition, resulting in an activation. Motor evoked potential area decreased over the course of the short foreperiod, but not over the long foreperiod, revealing that time preparation involves the inhibition of the cortico-spinal pathway. We propose that cortico-spinal inhibition secures the development of cortical activation, preventing erroneous premature responding.     

Motor recovery following stroke: a transcranial magnetic stimulation study.

OBJECTIVES: To verify the usefulness of early recording of motor evoked potentials (MEPs) in predicting motor outcome after stroke and to investigate the neural mechanisms underlying functional recovery following stroke. METHODS: We performed a comparative analysis of the behaviour of motor responses evoked by transcranial magnetic stimulation (TMS) of the ipsilateral and contralateral motor cortex in the affected and unaffected thenar muscles of 21 consecutive patients with acute stroke. RESULTS: According to the behaviour of MEPs in the affected muscles, patients could be divided into 3 groups: (a) 10 subjects with absent responses to TMS of both the damaged and undamaged hemisphere, whose motor recovery was poor and related to the size of MEPs on the normal side; (b) 5 subjects with larger MEPs upon TMS of the ipsilateral (undamaged) than of the contralateral (damaged) cortex, whose good recovery possibly resulted from the emergence of ipsilateral pathways; (c) 6 subjects with larger MEPs in the affected than in the unaffected muscles, whose good recovery was possibly subserved by alternative circuits taking over cortical deafferentation. CONCLUSIONS: Early MEP recording in acute stroke provides useful information on the clinical prognosis and the different mechanisms of motor recovery.     

Cortical excitability in cryptogenic localization-related epilepsy: interictal transcranial magnetic stimulation studies

PURPOSE: To assess whether single-and paired-pulse transcranial magnetic stimulation (TMS) can measure the interictal brain excitability of medicated patients with cryptogenic localization related epilepsy (CLE). Changes in the balance between excitation and inhibition are the core phenomena in focal epileptogenesis. TMS can assess this balance in the primary motor cortex. METHODS: We selected 18 patients with CLE and similar clinical features in whom we located the epileptogenic area reliably, with 11 age-and sex-matched healthy controls. For both motor cortices, we determined the threshold to TMS, the duration of the cortical silent period, and the corticocortical inhibition and facilitation curve. RESULTS: TMS was safe. The more antiepileptic drugs (AEDs) taken by the patients, the higher their threshold to TMS. The silent period duration failed to show significant changes. On paired TMS, a cluster analysis identified a homogeneous subgroup of patients (n = 7) who showed a significantly defective corticocortical inhibition and excess facilitation. With respect to the epileptogenic area, the phenomenon was bilateral in four of these patients, ipsilateral in two, and contralateral in one. The phenomenon was independent of AEDs and many other clinical variables. However, this patient group had a higher seizure frequency and a higher proportion of electroencephalograms (EEGs) showing interictal generalized epileptic discharges than the rest of the patients. CONCLUSION: Paired TMS provided a valuable pathophysiologic insight into the interictal excitatory state of the cortex in CLE. This method can potentially supply useful prognostic clinical information.